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1,200 | 29,108,777 | The findings of this investigation indicate that antioxidant treatment is effective clinical ly for DN treatment in T2DM patient . | BACKGROUND Diabetic nephropathy ( DN ) is one of the leading causes of morbidity and mortality amongst the diabetes mellitus patients .
Oxidative stress played a major role in the pathogenesis of DN .
Many studies reported that therapies with antioxidant potential have a beneficial effect on DN but there is conflicting evidence amongst them .
OBJECTIVE To eluci date the association between antioxidant and DN and to develop a robust evidence for clinical decisions by conducting systematic review s and meta- analysis . | Background : The Norfolk Quality of Life Question naire-Diabetic Neuropathy ( Norfolk QOL-DN ) is a vali date d comprehensive question naire design ed to capture the entire spectrum of DN related to large fiber , small fiber , and autonomic neuropathy not captured in existing instruments . We aim ed to determine if the Norfolk QOL-DN could be used to capture changes in QOL that correlate with nerve fiber-specific objective measures in a placebo-controlled trial of two agents that affect different nerve fibers . Methods : Sixty patients with DN were allocated to treatment on ruboxistaurin ( RBX ) ( n = 18 ) , topiramate ( TPX ) ( n = 18 ) , or placebo ( n = 18 ) . QOL-DN was administered and objective measures of nerve function were performed at entry and end of the study period . Results : Total QOL scores improved significantly in the active treatment groups ( RBX −9.56 ± 4.13 ; TPX −12.22 ± 2.76 ) but not in placebo ( −5.56 ± 3.49 ) . There were differences in nerve function improvement between treatments . Neurological symptom scores ( NSS ) improved with TPX from 5.5 ( 2.3 ) to 4.3 ( 0.65 ) ( p = .007 ) , sensory scores improved with TPX from 15.5 ( 1.79 ) to 8.3 ( 1.19 ) ( p < .001 ) , motor scores did not change , and sensory and motor impairment scores improved with TPX from 18.8 ( 2.15 ) to 12.1 ( 1.71 ) ( p = .003 ) . Total neuropathy scores ( TNS ) improved with TPX from 24.35 ( 2.61 ) to 16.35 ( 2.02 ) ( p = .001 ) . Neuropathy total symptom score−6 ( NTSS−6 ) changes were significant for both treatments : RBX 4.38 ( 0.75 ) to 1.49 ( 0.38 ) ( p < .001 ) and TPX 7.57 ( 1.3 ) to 4.26 ( 0.95 ) ( p = .036 ) . Changes in QOL-DN large fiber subscores correlated ( Spearman 's rank ) significantly with changes in NTSS-6 ( r = 0.55 ; p < .0001 ) , NSS ( r = 0.31 ; p < .04 ) , neuropathy impairment score ( NIS ) ( r = 0.35 ; p < .02 ) , and TNS ( r = 0.48 ; p < .0006 ) . Changes in QOL-DN small fiber subscores correlated significantly with changes in NTSS-6 total scores ( r = 0.40 ; p < .005 ) and intraepidermal nerve fiber density ( IENFD ) ( r = −0.29 ; p < .05 ) . Conclusion : Ruboxistaurin produced significant improvement in large fiber measures while TPX produced significant changes in small fiber measures . The Norfolk QOL-DN tool differentiated between these changes captured in the fiber-specific domains . Correlations were found between objective measures of neuropathy and total QOL , but those with nerve fiber domain scores were modest and reinforce the need to quantify QOL as an endpoint in neuropathy independent of other measures Background / Aims : Bardoxolone methyl , a novel synthetic triterpenoid , induces Nrf2 , a transcription factor known to play a key role in decreasing oxidative stress and the production of pro-inflammatory molecules . Methods : This exploratory multi-center , open-label study assessed the clinical activity and safety of bardoxolone methyl in 20 patients with moderate to severe chronic kidney disease and type 2 diabetes . Patients received 25 mg of bardoxolone methyl daily for 28 days , followed by 75 mg daily for another 28 days . Results : The study achieved its primary efficacy endpoint , as demonstrated by a significant increase from baseline in estimated glomerular filtration rate ( eGFR ) of 7.2 ml/min/1.73 m2 ( p < 0.001 ) . Improvements were seen in approximately 90 % of patients and showed a dose- and time-dependent increase in eGFR . The eGFR change paralleled a significant reduction in serum creatinine ( –0.3 mg/dl ) and blood urea nitrogen ( –4.9 mg/dl ) , along with an increase in creatinine clearance ( + 14.6 ml/min/1.73 m2 ) , without a change in the 24-hour creatinine excretion rate . Markers of vascular injury and inflammation were improved by treatment with bardoxolone . No life-threatening adverse events or drug-related serious adverse events were reported . Conclusions : The results describe an apparent increase in kidney function following relatively short-term treatment with bardoxolone methyl , a promising new agent that warrants placebo-controlled studies to define its long-term effects on renal function Prior research has shown that in experimental diabetes mellitus , green tea reduces albuminuria by decreasing podocyte apoptosis through activation of the WNT pathway . We investigated the effect of green tea polyphenols ( GTP ) on residual albuminuria of diabetic subjects with nephropathy . We conducted a r and omised , double-blind study in 42 diabetic subjects with a urinary albumin-creatinine ratio ( UACR ) > 30 mg/g , despite administration of the maximum recommended dose of renin-angiotensin ( RAS ) inhibition . Patients were r and omly assigned to two equal groups to receive either GTP ( containing 800 mg of epigallocatechin gallate , 17 with type 2 diabetes and 4 with type 1 diabetes ) or placebo ( 21 with type 2 diabetes ) for 12 weeks . Treatment with GTP reduced UACR by 41 % , while the placebo group saw a 2 % increase in UACR ( p = 0.019 ) . Podocyte apoptosis ( p = 0.001 ) and in vitro albumin permeability ( p < 0.001 ) were higher in immortalized human podocytes exposed to plasma from diabetic subjects compared to podocytes treated with plasma from normal individuals . In conclusion , GTP administration reduces albuminuria in diabetic patients receiving the maximum recommended dose of RAS . Reduction in podocyte apoptosis by activation of the WNT pathway may have contributed to this effect Background / Aims : Treatments of diabetic nephropathy ( DN ) delay the onset of end-stage renal disease . We report the results of safety/tolerability studies in patients with overt nephropathy and type 1/type 2 diabetes treated with pyridoxamine , a broad inhibitor of advanced glycation . Methods : The two 24-week studies were multicenter Phase 2 trials in patients under st and ard-of-care . In PYR-206 , patients were r and omized 1:1 and had baseline serum creatinine ( bSCr ) ≤2.0 mg/dl . In PYR-205/207 , r and omization was 2:1 and bSCr was ≤2.0 for PYR-205 and ≧2.0 but ≤3.5 mg/dl for PYR-207 . Treated patients ( 122 active , 90 placebo ) received 50 mg pyridoxamine twice daily in PYR-206 ; PYR-205/207 patients were escalated to 250 mg twice daily . Results : Adverse events were balanced between the groups ( p = NS ) . Slight imbalances , mainly in the PYR-205/207 groups , were noted in deaths ( from diverse causes , p = NS ) and serious adverse events ( p = 0.05 ) that were attributed to pre-existing conditions . In a merged data set , pyridoxamine significantly reduced the change from baseline in serum creatinine ( p < 0.03 ) . In patients similar to the RENAAL/IDNT studies ( bSCr ≧1.3 mg/dl , type 2 diabetes ) , a treatment effect was observed on the rise in serum creatinine ( p = 0.007 ) . No differences in urinary albumin excretion were seen . Urinary TGF-β1 also tended to decrease with pyridoxamine ( p = 0.049 ) as did the CML and CEL AGEs . Conclusion : These data provide a foundation for further evaluation of this AGE inhibitor in DN Inflammation is a central component of progressive chronic kidney disease ( CKD ) . Iron promotes oxidative stress and inflammatory response in animals and promotes progressive CKD . Parenteral iron provokes oxidative stress in patients with CKD ; however , its potential to provoke an inflammatory response is unknown . In 20 veterans with CKD , 100 mg iron sucrose was administered intravenously over 5 min and urinary excretion rate and plasma concentration of monocyte chemoattractant protein-1 ( MCP-1 ) were measured at timed intervals over 24 h. Patients were then r and omized to placebo or N-acetyl cysteine ( NAC ) 600 mg b.i.d . and the experiment was repeated at 1 week . Iron sucrose markedly increased plasma concentration and urinary excretion rate of MCP-1 at baseline and at 1 week visits ( P < 0.0001 for time effect ) . Urinary excretion peaked at 30 min and plasma concentration at 15 min . Plasma MCP-1 concentration fell from 164 + /- 17.7 to 135 + /- 17.7 pg/ml with NAC , whereas it remained unchanged from 133 + /- 12.5 to 132 + /- 17.7 pg/ml with placebo ( P=0.001 for visit x antioxidant drug interaction ) . There was a reduction in MCP-1 urinary excretion rate from visit 1 to 2 . At the baseline visit , the urinary excretion rate averaged 305 + /- 66 pg/min and at the second visit 245 + /- 67 pg/min ( mean difference 60 + /- 28 pg/min , P = 0.030 ) . There was no improvement in urinary MCP-1 excretion with NAC . In conclusion , iron sucrose causes rapid and transient generation and /or release of MCP-1 plasma concentration and increases urinary excretion rate , and systemic MCP-1 level but the urinary excretion rate is not abrogated with the antioxidant NAC . These results may have implication s for the progression of CKD with parenteral iron Background Arterial stiffness is increased in patients with CKD and is a powerful predictor of cardiovascular morbidity and mortality . Use of the xanthine oxidase inhibitor allopurinol has been shown to improve endothelial function , reduce left ventricular hypertrophy and possibly improve cardiovascular outcome . We explored the relationship between use of allopurinol and arterial stiffness in patients with chronic kidney disease ( CKD ) . Methods Cross-sectional observational study of 422 patients with CKD with evidence of , or at high risk of , renal disease progression . Arterial stiffness was determined by carotid-femoral pulse wave velocity ( PWV ) . Results The mean age was 63±16 years , median estimated glomerular filtration rate was 25 ( interquartile range : 19–31 ) ml/min/1.73 m2 and mean PWV was 10.2±2.4 m/s . Seventy-seven patients ( 18 % ) were receiving regular allopurinol , 61 % at a dose of 100 mg/day ( range : 50–400 mg/day ) . Patients receiving allopurinol had significantly lower peripheral pulse pressure , central pulse pressure , central systolic blood pressure , serum uric acid level tissue advanced glycation end product levels but comparable high-sensitivity C-reactive protein levels . Use of allopurinol was associated with lower PWV . After adjusting for age , gender , ethnicity , tissue advanced glycation end product level , peripheral pulse pressure , smoking pack years , presence of diabetes mellitus and use of angiotensin converting enzyme inhibitor or angiotensin II receptor blocker , the use of allopurinol remained a significant independent determinant of PWV ( mean difference : −0.63 m/s ; 95 % CI , −0.09 to −1.17 m/s , p = 0.02 ) . Conclusion In patients with CKD , use of allopurinol is independently associated with lower arterial stiffness . This study provides further justification for a large definitive r and omised controlled trial examining the therapeutic potential of allopurinol to reduce cardiovascular risk in people with CKD Pyridoxamine dihydrochloride ( Pyridorin , NephroGenex ) inhibits formation of advanced glycation end products and scavenges reactive oxygen species and toxic carbonyls , but whether these actions translate into renoprotective effects is unknown . In this double-blind , r and omized , placebo-controlled trial , we r and omly assigned 317 patients with proteinuric type 2 diabetic nephropathy to twice-daily placebo ; Pyridorin , 150 mg twice daily ; or Pyridorin , 300 mg twice daily , for 52 weeks . At baseline , the mean age ± SD was 63.9±9.5 years , and the mean duration of diabetes was 17.6±8.5 years ; the mean serum creatinine level was 2.2±0.6 mg/dl , and the mean protein-to-creatinine ratio was 2973±1932 mg/g . Regarding the primary end point , a statistically significant change in serum creatinine from baseline to 52 weeks was not evident in either Pyridorin group compared with placebo . However , analysis of covariance suggested that the magnitude of the treatment effect differed by baseline renal function . Among patients in the lowest tertile of baseline serum creatinine concentration , treatment with Pyridorin associated with a lower average change in serum creatinine concentration at 52 weeks ( 0.28 , 0.07 , and 0.14 mg/dl for placebo , Pyridorin 150 mg , and Pyridorin 300 mg , respectively ; P=0.05 for either Pyridorin dose versus placebo ) ; there was no evidence of a significant treatment effect in the middle or upper tertiles . In conclusion , this trial failed to detect an effect of Pyridorin on the progression of serum creatinine at 1 year , although it suggests that patients with less renal impairment might benefit Background Progression to chronic renal failure involves accelerated atherosclerosis and vascular calcification . Oxidative stress and endothelial dysfunction play a role in renal failure pathophysiology . In addition to improving vascular health and function , proanthocyanidins have been shown to exert renoprotective effects in animal models . Thus we hypothesize that proanthocyanidins may contribute to the maintenance of healthy renal function . Objective Determine the association of habitual proanthocyanidin intake with renal function and the risk of clinical renal outcomes in a population of elderly women . Design 948 women aged over 75 y , free of prevalent renal disease at baseline , were r and omly selected from ambulant Caucasian women . Proanthocyanidin consumption was determined using a vali date d food frequency question naire and the United States Department of Agriculture proanthocyanidin food content data base . Fasting serum cystatin C and creatinine were assessed at baseline . Renal failure hospitalisations and deaths were assessed over 5 years of follow-up through the Western Australia Data Linkage System . Results Compared to participants with low consumption , participants in the highest tertile of proanthocyanidin intake had a 9 % lower cystatin C concentration ( P<0.001 ) . High proanthocyanidin consumers were at 50 % lower risk of moderate chronic kidney insufficiency , and 65 % lower risk of experiencing a 5-year renal disease event ( P<0.05 ) . These relationships remained significant following adjustment for renal disease risk factors and diet-related potential confounders . Conclusion Increased consumption of proanthocyanidins was associated with better renal function and substantially reduced renal associated events , which has been supported by mechanistic and animal model data . Proanthocyanidin intake should be further examined as a dietary contributor to better renal health BACKGROUND This study was undertaken to determine whether use of the direct renin inhibitor aliskiren would reduce cardiovascular and renal events in patients with type 2 diabetes and chronic kidney disease , cardiovascular disease , or both . METHODS In a double-blind fashion , we r and omly assigned 8561 patients to aliskiren ( 300 mg daily ) or placebo as an adjunct to an angiotensin-converting-enzyme inhibitor or an angiotensin-receptor blocker . The primary end point was a composite of the time to cardiovascular death or a first occurrence of cardiac arrest with resuscitation ; nonfatal myocardial infa rct ion ; nonfatal stroke ; unplanned hospitalization for heart failure ; end-stage renal disease , death attributable to kidney failure , or the need for renal-replacement therapy with no dialysis or transplantation available or initiated ; or doubling of the baseline serum creatinine level . RESULTS The trial was stopped prematurely after the second interim efficacy analysis . After a median follow-up of 32.9 months , the primary end point had occurred in 783 patients ( 18.3 % ) assigned to aliskiren as compared with 732 ( 17.1 % ) assigned to placebo ( hazard ratio , 1.08 ; 95 % confidence interval [ CI ] , 0.98 to 1.20 ; P=0.12 ) . Effects on secondary renal end points were similar . Systolic and diastolic blood pressures were lower with aliskiren ( between-group differences , 1.3 and 0.6 mm Hg , respectively ) and the mean reduction in the urinary albumin-to-creatinine ratio was greater ( between-group difference , 14 percentage points ; 95 % CI , 11 to 17 ) . The proportion of patients with hyperkalemia ( serum potassium level , ≥6 mmol per liter ) was significantly higher in the aliskiren group than in the placebo group ( 11.2 % vs. 7.2 % ) , as was the proportion with reported hypotension ( 12.1 % vs. 8.3 % ) ( P<0.001 for both comparisons ) . CONCLUSIONS The addition of aliskiren to st and ard therapy with renin-angiotensin system blockade in patients with type 2 diabetes who are at high risk for cardiovascular and renal events is not supported by these data and may even be harmful . ( Funded by Novartis ; ALTITUDE Clinical Trials.gov number , NCT00549757 . ) Glycosaminoglycans or sulodexide has shown benefits in early experimental diabetic nephropathy ( DN ) models , but its efficacy in patients with early stage of DN is unknown . Methods . Twenty patients were r and omly assigned to the placebo group and another 20 patients were r and omly assigned to receive sulodexide 100 mg/day for 14 weeks . Primary outcome was a change of urinary TGF-beta1 , albuminuria , and glomerular filtration rate ( GFR ) . All patients had stable metabolic profiles for at least 90 days before r and omization . Results . Urinary TGF-beta1 increased significantly in the placebo group but did not change significantly in the sulodexide group . Additionally , the mean change of urine TGF-beta1 in the placebo group was significantly higher than that in the sulodexide group ( 8.44 ± 9.21 versus 2.17 ± 6.96 pg/mg Cr , P = 0.02 ) . Mean changes of urinary albumin were 15.05 ± 30.09 μg/mg Cr ( P = 0.038 ) in the placebo group and 13.89 ± 32.25 μg/mg Cr ( P = 0.069 ) in the sulodexide group . No consistent patterns of side effects were observed . Conclusion . In this 14-week trial , benefits of sulodexide in preventing the increase of urinary TGF-beta1 were observed in patients with normoalbuminuric type 2 diabetes . The study suggests that sulodexide treatment may provide additional renoprotection in early stage DN . This trial is registered with TCTR20140806001 Abstract Objective . End-stage renal disease ( ESRD ) due to type 2 diabetic nephropathy is a very common condition which is increasing in prevalence , and is associated with high global levels of mortality and morbidity . Both proteinuria and transforming growth factor-β ( TGF-β ) may contribute to the development of ESRD in patients with diabetic nephropathy . Experimental studies indicate that turmeric improves diabetic nephropathy by suppressing TGF-β . Therefore , this study investigated the effects of turmeric on serum and urinary TGF-β , interleukin-8 ( IL-8 ) and tumour necrosis factor-α ( TNF-α ) , as well as proteinuria , in patients with overt type 2 diabetic nephropathy . Material and methods . A r and omized , double-blind and placebo-controlled study was carried out in the Diabetes Clinic of the Outpatient Department of Shiraz University of Medical Sciences on 40 patients with overt type 2 diabetic nephropathy , r and omized into a trial group ( n = 20 ) and a control group ( n = 20 ) . Each patient in the trial group received one capsule with each meal containing 500 mg turmeric , of which 22.1 mg was the active ingredient curcumin ( three capsules daily ) for 2 months . The control group received three capsules identical in colour and size containing starch for the same 2 months . Results . Serum levels of TGF-β and IL-8 and urinary protein excretion and IL-8 decreased significantly comparing the pre- and post-turmeric supplementation values . No adverse effects related to turmeric supplementation were observed during the trial . Conclusion . Short-term turmeric supplementation can attenuate proteinuria , TGF-β and IL-8 in patients with overt type 2 diabetic nephropathy and can be administered as a safe adjuvant therapy for these patients BACKGROUND Serum phosphorus ( P ) and the product of serum calcium x serum P ( Ca x P ) , are frequently elevated in end-stage renal disease patients on maintenance hemodialysis ( HD ) . Elevated P and Ca x P have been associated with vascular calcification in dialysis patients . OBJECTIVE [ corrected ] To examine the role of P and Ca x P as risk factors for incident peripheral vascular disease ( PVD ) in HD patients with pre-existing CVD . METHODS This nested case-control study is drawn from the 11 incident PVD events reported in the cohort of the Secondary prevention with antioxidants of cardiovascular disease in end-stage renal disease ( SPACE ) : a r and omized placebo-controlled trial . PVD was defined clinical ly and confirmed ultrasonographically . Each individual with a PVD event was matched for SPACE treatment group ( vitamin E or placebo ) , age ( in 4-year categories ) and gender with two individuals who had no CVD end point during the follow-up period . RESULTS Serum P and Ca x P levels were significantly higher in PVD patients than in controls . In univariate logistic regression analysis , only serum P predicted PVD in this population ( OR 2.02 , 95 % CI 1.07 - 3.81 , p = 0.03 ) . In multivariate analysis , adjustment was made for variables dissimilar by PVD status including underlying renal disease , diabetes , smoking , history of angina pectoris , prescription for vitamin D3 , erythropoietin , calcium channel blockers and aspirin . In this model , serum P remained the only significant predictor of incident PVD ( OR 2.4 , 95 % CI 1.01 - 5.74 , p = 0.04 ) . CONCLUSIONS Findings of the present study are consistent with a role for serum P and Ca x P in the pathogenesis of PVD in HD patients AIM To examine the effects of glibenclamide and repaglinide on glucose stimulated insulin release , incretins , oxidative stress and cell adhesion molecules in patients with type 2 diabetes suboptimally treated with metformin . METHODS A r and omized clinical trial was performed recruiting 27 subjects ( HbA(1c ) between 7.5 and 10.5 % ) free from cardiovascular and renal disease . Glucose , insulin , C-peptide , glucagon-like peptide-1 ( GLP-1 ) , glucose-dependent insulinotropic peptide ( GIP ) , total antioxidant status , F(2)-isoprostane , interleukin-6 and cell adhesion molecules were measured during an oral glucose load at baseline and after eight weeks of treatment . The areas under the curve were analysed at 45 , 60 and 120 min ( AUC(45 ) , AUC(60 ) , AUC(120 ) ) . RESULTS Significant improvements in glucose were observed with repaglinide ( HBA(1c ) : -1.5 % , fasting glucose : -2.8 mmol/L , 2-h glucose : -3.7 mmol/L , AUC(120 ) : -18.9 % ) and glibenclamide ( -1.0 % , -2.2 mmol/L , -2.5 mmol/L , -17.5 % ) . Repaglinide was also associated with an increase in the AUC(60 ) and AUC(120 ) for insulin ( + 56 % , + 61 % ) and C-peptide ( + 41 % , + 36 % ) . GLP-1 , GIP , IL-6 , ICAM-1 and E-selectin levels did not change in either group . No association was observed between GLP-1 , GIP-1 and plasma markers of oxidative stress . CONCLUSION Repaglinide is associated with improved postpr and ial glycaemic control via insulin and C-peptide release . We observed no direct effects of glibenclamide or repaglinide on plasma levels of GLP-1 or GIP . We observed no associations of GLP-1 and GIP with plasma markers of oxidative stress This study aims to evaluate efficacy and safety of Nigella sativa oil supplementation in patients with chronic kidney disease Stage 3 and 4 due to diabetic nephropathy . It was a prospect i ve , comparative , and open-label study . Patients were r and omized into two groups . Group 1 ( Control ) received conservative management of diabetic nephropathy , whereas Group 2 ( Test ) received N. sativa oil ( 2.5 mL , once daily and per orally ) along with conservative management for 12 weeks . Blood glucose , hemogram , and kidney function test were done at 0 , 6 , and 12 weeks of treatment . Significance of differences between pre- and post-treatment values in each group was assessed using Student 's paired t-test and between the groups using unpaired t-test . We found a drop in blood glucose , serum creatinine , blood urea , and 24 h total urinary protein levels and a rise in glomerular filtration rate , 24 h total urinary volume , and hemoglobin level in the treatment group compared to the control group Liver fibrosis , a common condition occurring during the evolution of almost all chronic liver diseases , is the consequence of hepatocyte injury that leads to the activation of Kupffer cells and hepatic stellate cells ( HSC ) . Silymarin ( Si ) is a herbal product widely used for its hepatoprotective potential . Our study aims to investigate the effects of two different doses of Silymarin on a CCl4-induced model of liver fibrosis with a focus on the early stages of liver injury . Fifty Wistar rats were r and omly divided into five groups ( n=10 ) : control group ( sunflower oil twice a week ) ; CMC group ( carboxymethyl cellulose five times a week , sunflower oil twice a week ) ; CCl4 group ( CCl4 in sunflower oil , by gavage , twice a week ) ; CCl4+Si 50 group ( CCl4 twice a week , Silymarin 50 mg/b.w . in CMC five times a week ) ; and CCl4+Si 200 group ( similar to the previous group , with Si 200 mg/b.w . ) . One month after the experiment began we explored hepato-cytolysis ( aminotransferases and lactate dehydrogenase ) , oxidative stress , fibrosis ( histological score , hyaluronic acid ) , markers of HSC activation ( transforming growth factor β1 [ TGF-β1 ] , and α-smooth muscle actin [ α-SMA ] expression by western blot ) and activation of Kupffer cells by immunohistochemistry . Our data showed that Si 50 mg/b.w . had the capacity of reducing oxidative stress , hepato-cytolysis , fibrosis , activation of Kupffer cells , and the expression of α-SMA and TGF-β1 with better results than Si 200 mg/b.w . Thus , the usual therapeutic dose of Silymarin , administered in the early stages of fibrotic changes is capable of inhibiting the fibrogenetic mechanism and the progression of initial liver fibrosis AIMS Elevated levels of urinary albumin excretion rate ( AER ) predict high risk for progressing to end-stage renal disease . In streptozotocin-induced diabetes , supplementation with vitamin C or E reduces albuminuria and glomerular hypertrophy . We tested the hypothesis that supplementation of both vitamin C and E in pharmacological doses lowers AER in Type 2 diabetic patients with persistent micro/macroalbuminuria . METHODS Thirty Type 2 diabetic patients with AER 30 - 300 mg/24 h were included in a double-blind r and omised , cross-over trial . Patients received vitamin C ( 1250 mg ) and vitamin E ( 680 IU ) per day or matching placebo for 4 weeks with a 3-week wash-out period between treatment periods in r and om order . RESULTS Combined treatment with vitamin C and E reduced AER by 19 % ( 95 % CI 6 - 34 % ) ( p = 0.04 ) , geometric mean 197 mg/24 h ( 95 % CI 114 - 341 mg/24 h ) vs. 243 mg/24 h ( 146 - 404 mg/24 h ) . No changes were seen in serum creatinine , haemoglobin A1C or blood pressure . Fasting plasma concentrations of vitamin C and E increased in all patients during active treatment ( mean vitamin C 79.4 micromol/L ( SD 27.8 ) vs. 41.9 micromol/L ( 18.4 ) and vitamin E 47.0 micromol/L ( 19.8 ) vs. 29.5 micromol/L ( 15.3 ) , P < 0.000001 ) . Except for two patients that started additional blood pressure lowering treatment during the run-in period , no changes in medication , food and exercise habits or in the number of smokers occurred during the study . CONCLUSION Short-term treatment with vitamin C and E in pharmacological doses lowers AER in Type 2 diabetic patients with micro/macroalbuminuria . Further long-term , large-scale studies of this albuminuria reducing treatment modality are warranted BACKGROUND Although inhibitors of the renin-angiotensin-aldosterone system can slow the progression of diabetic kidney disease , the residual risk is high . Whether nuclear 1 factor ( erythroid-derived 2)-related factor 2 activators further reduce this risk is unknown . METHODS We r and omly assigned 2185 patients with type 2 diabetes mellitus and stage 4 chronic kidney disease ( estimated glomerular filtration rate [ GFR ] , 15 to < 30 ml per minute per 1.73 m(2 ) of body-surface area ) to bardoxolone methyl , at a daily dose of 20 mg , or placebo . The primary composite outcome was end-stage renal disease ( ESRD ) or death from cardiovascular causes . RESULTS The sponsor and the steering committee terminated the trial on the recommendation of the independent data and safety monitoring committee ; the median follow-up was 9 months . A total of 69 of 1088 patients ( 6 % ) r and omly assigned to bardoxolone methyl and 69 of 1097 ( 6 % ) r and omly assigned to placebo had a primary composite outcome ( hazard ratio in the bardoxolone methyl group vs. the placebo group , 0.98 ; 95 % confidence interval [ CI ] , 0.70 to 1.37 ; P=0.92 ) . In the bardoxolone methyl group , ESRD developed in 43 patients , and 27 patients died from cardiovascular causes ; in the placebo group , ESRD developed in 51 patients , and 19 patients died from cardiovascular causes . A total of 96 patients in the bardoxolone methyl group were hospitalized for heart failure or died from heart failure , as compared with 55 in the placebo group ( hazard ratio , 1.83 ; 95 % CI , 1.32 to 2.55 ; P<0.001 ) . Estimated GFR , blood pressure , and the urinary albumin-to-creatinine ratio increased significantly and body weight decreased significantly in the bardoxolone methyl group , as compared with the placebo group . CONCLUSIONS Among patients with type 2 diabetes mellitus and stage 4 chronic kidney disease , bardoxolone methyl did not reduce the risk of ESRD or death from cardiovascular causes . A higher rate of cardiovascular events with bardoxolone methyl than with placebo prompted termination of the trial . ( Funded by Reata Pharmaceuticals ; BEACON Clinical Trials.gov number , NCT01351675 . ) |
1,201 | 22,258,958 | AUTHORS ' CONCLUSIONS There is no reliable evidence suggesting which could be the most effective interventions for treating peri-implantitis .
This is not to say that currently used interventions are not effective .
Follow-up longer than 1 year suggested recurrence of peri-implantitis in up to 100 % of the treated cases for some of the tested interventions .
As this can be a chronic disease , re-treatment may be necessary . | BACKGROUND One of the key factors for the long-term success of oral implants is the maintenance of healthy tissues around them .
Bacterial plaque accumulation induces inflammatory changes in the soft tissues surrounding oral implants and it may lead to their progressive destruction ( peri-implantitis ) and ultimately to implant failure .
Different treatment strategies for peri-implantitis have been suggested , however it is unclear which are the most effective .
OBJECTIVES To identify the most effective interventions for treating peri-implantitis around osseointegrated dental implants . | OBJECTIVES The aim of the present case series was to evaluate the 2-year results obtained following treatment of peri-implantitis lesions using either a nanocrystalline hydroxyapatite ( NHA ) or a natural bone mineral in combination with a collagen membrane ( NBM+CM ) . MATERIAL AND METHODS Twenty-two patients suffering from moderate peri-implantitis ( n=22 intra-bony defects ) were r and omly treated with ( i ) access flap surgery ( AFS ) and the application of NHA , or with AFS and the application of NBM+CM . Clinical parameters were recorded at baseline and after 12 , 18 , and 24 months of non-submerged healing . RESULTS Two patients from the NHA group were excluded from the study due to severe pus formation at 12 months . At 24 months , both groups revealed clinical ly important probing depth ( PD ) reductions ( NHA : 1.5+/-0.6 mm ; NBM+CM : 2.4+/-0.8 mm ) and clinical attachment level ( CAL ) gains ( NHA : 1.0+/-0.4 mm ; NBM+CM : 2.0+/-0.8 mm ) . However , these clinical improvements seemed to be better in the NBM+CM group ( difference between groups : PD reduction : 0.9+/-0.2 mm ; CAL gain : 1.0+/-0.3 mm ) . CONCLUSION Both treatment procedures have shown efficacy over a period of 24 months , however , the application of NBM+CM may result in an improved outcome of healing AIM This r and omized clinical trial presents a 12-month follow-up of the clinical and microbiological results after application of minocycline microspheres as an adjunct to mechanical treatment of incipient peri-implant infections compared with an adjunctive treatment using 1 % chlorhexidine gel application . MATERIAL AND METHODS Thirty-two subjects with probing depth > or = 4 mm , combined with bleeding and /or exu date on probing and presence of putative pathogenic bacteria were given oral hygiene instructions and mechanical treatment of infected areas adjacent to implants . The subjects were then r and omly assigned adjunctive subgingival antimicrobial treatment using either chlorhexidine gel or minocycline microspheres . Sixteen patients in the minocycline group and 14 in the chlorhexidine group completed the study . Follow-up examinations were carried out after 10 days , 1 , 2 , 3 , 6 , 9 and 12 months . RESULTS The adjunctive use of minocycline microspheres result ed in improvements of probing depths and bleeding scores , whereas the adjunctive use of chlorhexidine only result ed in limited reduction of bleeding scores . For the deepest sites of the treated implants in the minocycline group , the mean probing depth was reduced from 5.0 to 4.4 mm at 12 months . This study could not show any significant difference in the levels of bacterial species or groups at any time point between the two antimicrobial agents tested . The present findings encourage further studies on adjunctive use of minocycline microspheres in the treatment of peri-implant lesions . CONCLUSIONS The use of a local antibiotic as an adjunct to mechanical treatment of incipient peri-implantitis lesions demonstrated improvements in probing depths that were sustained over 12 months This report presents the clinical results three months after application of minocycline microspheres as an adjunct to mechanical treatment of incipient peri-implant infections compared to adjunctive treatment employing 1 % chlorhexidine gel application . Sixteen patients in the minocycline group and 14 in the chlorhexidine group completed the study . Each patient had one or more implants with probing depth > or = 4 mm combined with bleeding and /or exu date on probing and presence of putative pathogenic bacteria . At baseline , patients were r and omly assigned to minocycline or chlorhexidine treatment . Follow-up examinations were carried out after 10 , 30 , 60 and 90 days . The combined mechanical/antimicrobial treatment for the chlorhexidine group did not result in any reduction in probing depth and only limited reduction of bleeding scores . The adjunctive use of minocycline microspheres , on the other h and , result ed in improvements in both probing depths and bleeding scores . For the deepest sites of the treated implants , mean probing depth was reduced from 5.0 mm to 4.1 mm . The reductions in bleeding scores , although greater than for the chlorhexidine group , were modest . Thus , the question as to what extent the combined mechanical/minocycline treatment could be considered adequate for the treated lesions remains to be answered . The present short-term findings , however , encourage further studies with longer observation intervals on adjunctive use of minocycline microspheres in the treatment of periimplant lesions & NA ; Between 1994 and 1999 , 50 patients were treated with either profound parodontopathy ( 30 ) or periimplantitis ( 20 ) . Half of each of the two groups of patients was treated conventionally , and the other half was treated with laser support . Before the operation , microbiological examinations were carried out , in addition to registering the clinical findings and taking x‐rays . These procedures were repeated after the operation , and again after 6 , 12 , 24 , 36 , 48 , and 60 months . The surgical part of therapy for each half of the patient groups included surface decontamination with diode laser light ( 1‐watt output , maximum of 20 seconds ) in addition to conventional procedures . The values of the laser‐supported therapy were lower than those specified in the relevant literature . The relapse rate of the two diseases ( 13 % for the periimplantitis and 23 % for the parodontopathy group ) after 5 years was lower than the comparative values of research ed literature where decontamination was not included in the therapy . We think that integrating diode laser light decontamination in the approved treatment schemes for periimplantitis and parodontitis contributes considerably to the success of this therapy . ( Implant Dent 2000;9:247‐251 OBJECTIVES The study aim ed at investigating the impact of two surface debridement/decontamination ( DD ) methods on the clinical outcomes of combined surgical treatment of peri-implantitis . MATERIAL AND METHODS Thirty-two patients suffering from advanced peri-implantitis ( n=38 combined supra- and intra-bony defects ) were treated with flap surgery , granulation tissue removal , and implantoplasty at buccally and supracrestally exposed implant parts . The intra-bony aspects were r and omly allocated to surface DD using either ( i ) an Er : YAG laser ( ERL ) device , or ( ii ) plastic curets+cotton pellets+sterile saline ( CPS ) . In both groups , the intra-bony component was augmented with a natural bone mineral and covered with a collagen membrane . Clinical and radiographic parameters were recorded at baseline and after 6 months of non-submerged healing . RESULTS Two patients were lost during follow-up . At 6 months , ERL-treated sites failed to reveal higher reductions in mean bleeding on probing ( ERL : 47.8 ± 35.5 versus CPS : 55.0 ± 31.1 % ) and CAL values ( ERL : 1.5 ± 1.4 versus CPS : 2.2 ± 1.4 mm ) when compared with the CPS group . Both groups exhibited a comparable radiographic bone fill at the intra-bony defect component . CONCLUSION The study failed to demonstrate a significant impact of the method of surface DD on the clinical outcome following combined surgical therapy of advanced peri-implantitis lesions AIM To compare the effectiveness of treatment of peri-implantitis with a novel ultrasonic device , the Vector system , with that of subgingival debridement with carbon fiber curettes . MATERIAL AND METHODS The study , comprising 11 patients with at least two screw type implants with bleeding on probing ( BOP ) , probing pocket depth ( PPD ) > or = 5 mm , and at least 1.5 mm radiographic bone loss and exposed implant threads , was carried out as a single blind r and omized clinical trial . At baseline one r and omly chosen implant in each patient was treated by the Vector system ( test ) while the other implant ( control ) was treated by submucosal debridement with a carbon fiber curette . After 3 months , the same treatments were repeated . Plaque , BOP , and PPD were recorded on all implant surfaces at baseline , and after 3 and 6 months . Bone levels were recorded on radiographs taken prior to the start of the study , and after 6 months . RESULTS Oral hygiene around both test and control implants was improved at 3 and 6 months compared with baseline . At 6 months , four of the Vector-treated sites , and only one site treated with curettes , had stopped to bleed . In neither the test nor the control group , were there any differences between baseline and 6 months regarding PPD and bone levels . CONCLUSION Although there was a greater reduction in the number of sites with BOP following treatment with the Vector system than following instrumentation with carbon fiber curettes , there was no significant difference between the two methods This clinical study reports on the results of a new method in the treatment of peri-implantitis . The surfaces of 24 plasma flame-sprayed cylindric implants in 17 patients who were diagnosed with peri-implantitis were decontaminated with a combination of toluidine blue ( 100 micrograms/mL ) and laser irradiation at a wavelength of 906 nm . Bone defects were filled with autogenous bone using e-PTFE membranes for retention of the grafting material . Premature membrane exposure occurred in all patients after an average of 3 weeks ( + /- 10 days ) , which required immediate removal of the exposed membrane in 1 patient . Since the soft tissue showed minimal signs of inflammation , the membranes were left in situ for another 6 weeks in all other patients . The mean radiographic peri-implant bone gain was 2 mm + /- 1.90 mm after 9.5 months ( maxilla 2.5 mm + /- 2.38 mm ; m and ible 1.9 mm + /- 1.87 mm ) . Two implants around which the initial bone defect had already reached the basket had to be removed after 10 months and 35 months , respectively , despite radiographic evidence of improvement of the peri-implant defect . The longer the membrane stayed in situ , the more bone was gained , as long as the membrane was covered by soft tissue ( P = .01 ) . However , the longer an exposed membrane was left in place , the smaller the result ant bone gain ( P = .0001 ) . Therefore , despite the absence of clinical signs of inflammation , exposed membranes should be removed immediately . The short-term results of this study corroborate the efficacy of the applied treatment method in prolonging the service time of dental implants involved with peri-implantitis OBJECTIVES The aim of this prospect i ve cohort study was to compare two regenerative surgical treatment modalities for peri-implantitis . MATERIAL AND METHODS Thirty-six patients having a minimum of one osseointegrated implant , with a progressive loss of bone amounting to > or =3 threads ( 1.8 mm ) following the first year of healing , combined with bleeding and /or pus on probing , were involved in this study . The patients were assigned to two different treatment strategies . After surgical exposure of the defect , granulomatous tissue was removed and the infected implant surface was treated using 3 % hydrogen peroxide . The bone defects were filled with a bone substitute ( Algipore ) . In 17 patients ( Group 1 ) , a resorbable membrane ( Osseoquest ) was placed over the grafted defect before suturing . In 19 patients ( Group 2 ) , the graft was used alone . RESULTS One-year follow-up demonstrated clinical and radiographic improvements . Probing depths were reduced by 2.9 mm in Group 1 and by 3.4 mm in Group 2 . Defect fill amounted to 1.5 and 1.4 mm , respectively . There was no significant difference between the groups . CONCLUSION It is possible to treat peri-implant defects with a bone substitute , with or without a resorbable membrane OBJECTIVES The aim of this prospect i ve , parallel group design ed , r and omized controlled clinical study was to evaluate the effectiveness of an air-abrasive device ( AAD ) for non-surgical treatment of peri-implantitis . MATERIAL AND METHODS Thirty patients , each of whom displayed at least one implant with initial to moderate peri-implantitis , were enrolled in an oral hygiene program ( OHI ) and r and omly instrumented using either ( 1 ) AAD ( amino acid glycine powder ) or ( 2 ) mechanical debridement using carbon curets and antiseptic therapy with chlorhexidine digluconate ( MDA ) . Clinical parameters were measured at baseline , 3 and 6 months after treatment [ e.g. bleeding on probing ( BOP ) , probing depth ( PD ) , clinical attachment level ( CAL ) ] . RESULTS At 6 months , AAD group revealed significantly higher ( p<0.05 ; unpaired t-test ) changes in mean BOP scores when compared with MDA-treated sites ( 43.5 ± 27.7%versus 11.0 ± 15.7 % ) . Both groups exhibited comparable PD reductions ( AAD : 0.6 ± 0.6 mm versus MDA : 0.5 ± 0.6 mm ) and CAL gains ( AAD : 0.4 ± 0.7 mm versus MDA : 0.5 ± 0.8 mm ) ( p>0.05 ; unpaired t-test , respectively ) . CONCLUSIONS Within its limitations , the present study has indicated that ( i ) both treatment procedures result ed in comparable but limited CAL gains at 6 months , and ( ii ) OHI+AAD was associated with significantly higher BOP reductions than OHI+MDA The aim of this controlled , parallel design clinical study was to evaluate the effectiveness of an Er : YAG ( erbium-doped : yttrium , aluminum , and garnet ) laser for nonsurgical treatment of periimplantitis lesions . Twenty patients , each of whom displayed at least one implant with ( a ) moderate and ( b ) advanced periimplantitis ( n=40 implants ; IMZ , ITI , Spline Twist , ZL-Duraplant , Camlog ) , were r and omly instrumented nonsurgically using either ( 1 ) an Er : YAG laser ( 100 mJ/pulse , 10 Hz ) device ( LAS ) or ( 2 ) mechanical debridement using plastic curettes and antiseptic therapy with chlorhexidine digluconate ( 0.2 % ) ( C ) . The following clinical parameters were measured at baseline , 3 , 6 , and 12 months after treatment : plaque index , bleeding on probing ( BOP ) , probing depth , gingival recession , and clinical attachment level ( CAL ) . Mean BOP improved significantly in both groups at 3 , 6 , and 12 months ( a− lesions : P<0.001 and b− lesions : P<0.01 , respectively ) . After 3 and 6 months , the mean reduction of BOP was significantly higher in the LAS group when compared to the C group ( a− and b− lesions : P<0.01 and P<0.05 , respectively ) . At 3 and 6 months , both groups revealed significant CAL gains at a− and b− lesions ( P<0.01 , respectively ) . In both groups , however , the mean CAL at a− and b− lesions was not significantly different from the respective baseline values at 12 months ( P>0.05 , respectively ) . Although treatment of periimplantitis lesions with LAS result ed in a significantly higher BOP reduction than C , its effectiveness seemed to be limited to a period of 6 months , particularly at b− lesions OBJECTIVES The present case series aim ed at investigating the 4-year clinical outcomes following surgical regenerative therapy of peri-implantitis lesions using either a nanocrystalline hydroxyapatite ( NHA ) or a natural bone mineral in combination with a collagen membrane ( NBM+CM ) . MATERIAL S AND METHODS Twenty patients suffering from moderate peri-implantitis ( n=20 intrabony defects ) were r and omly treated with ( 1 ) access flap surgery ( AFS ) and the application of NHA ( n=9 ) , or with AFS and the application of NBM+CM ( n=11 ) . Clinical and radiographic ( R ) parameters were recorded at baseline ( R ) and after 36 and 48 ( R ) months of non-submerged healing . RESULTS One patient from the NBM+CM group was discontinued from the study due to severe pus formation at 36 months . Compared with NHA , the application of NBM+CM result ed in higher mean PD reductions ( NBM+CM : 2.5 + /- 0.9 mm versus NHA : 1.1 + /- 0.3 mm ) and clinical attachment-level gains ( NBM+CM : 2.0 + /- 1.0 mm versus NHA : 0.6 + /- 0.5 mm ) at 48 months . A radiographic bone fill was observed for five sites in the NHA group , and eight sites in the NBM+CM group . CONCLUSION While the application of NBM+CM result ed in clinical improvements over a period of 4 years , the long-term outcome obtained with NHA without barrier membrane must be considered as poor OBJECTIVES The aim of the present case series was to evaluate the healing of intrabony peri-implantitis defects following application of a nanocrystalline hydroxyapatite ( NHA ) or a bovine-derived xenograft in combination with a collagen membrane ( BDX+BG ) . MATERIAL AND METHODS Twenty-two patients having moderate peri-implantitis ( n=22 intrabony defects ) were r and omly treated with ( i ) access flap surgery ( AFS ) and the application of NHA , or with AFS and the application of BDX+BG . Clinical parameters were recorded at baseline and after 6 months of non-submerged healing . RESULTS Post-operative wound healing revealed that NHA compromized initial adhesion of the mucoperiosteal flaps in all patients . At 6 months after therapy , NHA showed a reduction in the mean PD from 7.0+/-0.6 to 4.9+/-0.6 mm and a change in the mean clinical attachment loss ( CAL ) from 7.5+/-0.8 to 5.7+/-1.0 mm . In the BDX+BC group , the mean PD was reduced from 7.1+/-0.8 to 4.5+/-0.7 mm and the mean CAL changed from 7.5+/-1.0 to 5.2+/-0.8 mm . CONCLUSION Within the limits of the present case series , it can be concluded that at 6 months after surgery both therapies result ed in clinical ly important PD reductions and CAL gains BACKGROUND Non-surgical peri-implantitis therapies appear to be ineffective . Limited data suggest that ER : YAG laser therapy improves clinical conditions . The present study aim ed at comparing the treatment effects between air-abrasive ( AM ) and Er : YAG laser ( LM ) mono-therapy in cases with severe peri-implantitis . MATERIAL S AND METHODS Twenty-one subjects in each group were r and omly assigned to one time intervention by an air-abrasive device or an Er : YAG laser . Clinical data were collected before treatment and at 6 months . Data analysis was performed using repeat univariate analysis of variance controlling for subject factors . RESULTS No baseline subject characteristic differences were found . Bleeding on probing and suppuration decreased in both the groups ( p<0.001 ) . The mean probing depth ( PPD ) reductions in the AM and LM groups were 0.9 mm ( SD 0.8 ) and 0.8 mm ( SD ± 0.5 ) , with mean bone-level changes ( loss ) of -0.1 mm ( SD ± 0.8 ) and -0.3 mm ( SD ± 0.9 ) , respectively ( NS ) . A positive treatment outcome , PPD reduction ≥0.5 mm and gain or no loss of bone were found in 47 % and 44 % in the AM and LM groups , respectively . CONCLUSIONS The clinical treatment results were limited and similar between the two methods compared with those in cases with severe peri-implantitis BACKGROUND Peri-implantitis is common in patients with dental implants . We performed a single-blinded longitudinal r and omized study to assess the effects of mechanical debridement on the peri-implant microbiota in peri-implantitis lesions . MATERIAL S AND METHODS An exp and ed checkerboard DNA-DNA hybridization assay encompassing 79 different microorganisms was used to study bacterial counts before and during 6 months following mechanical treatment of peri-implantitis in 17 cases treated with curettes and 14 cases treated with an ultrasonic device . Statistics included non-parametric tests and GLM multivariate analysis with p<0001 indicating significance and 80 % power . RESULTS At selected implant test sites , the most prevalent bacteria were : Fusobacterium nucleatum sp. , Staphylococci sp. , Aggregatibacter actinomycetemcomitans , Helicobacter pylori , and Tannerella forsythia . 30 min . after treatment with curettes , A. actinomycetemcomitans ( serotype a ) , Lactobacillus acidophilus , Streptococcus anginosus , and Veillonella parvula were found at lower counts ( p<0.001 ) . No such differences were found for implants treated with the ultrasonic device . Inconsistent changes occurred following the first week . No microbiological differences between baseline and 6-month sample s were found for any species or between treatment study methods in peri-implantitis . CONCLUSIONS Both methods failed to eliminate or reduce bacterial counts in peri-implantitis . No group differences were found in the ability to reduce the microbiota in peri-implantitis OBJECTIVE To evaluate the effects of local-delivery of 25 % metronidazol gel and mechanical cleaning using ultrasonic carbon fiber tip on dental implants with peri-implantitis . METHODS 27 implants with peri-implantitis were r and omly assigned to receiving either 25 % metronidazol gel treatment or carbon fiber tip ultrasonic scaling . All parameters including plaque index ( PLI ) , probing depth ( PD ) of pocket , sulcular bleeding index ( SBI ) , and BANA enzyme analysis were measured at baseline , 1 , 2 , 6 and 12 weeks after treatment . RESULTS Statistically significant decrease ( P < 0.05 ) in SBI , BANA test and PLI occurred in both treatment groups at all time intervals compared to baseline . PD had a decreasing tendency in both groups , but only metronidazole group reached statistically significant level ( P < 0.05 ) at 2 and 6 week intervals compared to baseline . None of the treatment modalities produced any side effects on the implant and peri-implant tissues . CONCLUSIONS Both 25 % metronidazol gel and mechanical cleaning using ultrasonic carbon fiber tip can be safely and effectively used in the treatment of peri-implant diseases The aim of this controlled , parallel design clinical study was to compare the effectiveness of an Er : YAG laser ( ERL ) to that of mechanical debridement using plastic curettes and antiseptic therapy for nonsurgical treatment of peri-implantitis . Twenty patients with moderate to advanced peri-implantitis lesions were r and omly treated with either ( 1 ) an ERL using a cone-shaped glass fiber tip at an energy setting of 100 mJ/pulse and 10 pps ( ERL ) , or ( 2 ) mechanical debridement using plastic curettes and antiseptic therapy with chlorhexidine digluconate ( 0.2 % ) ( C ) . The following clinical parameters were measured at baseline , 3 and 6 months after treatment by one blinded and calibrated examiner : Plaque index ( PI ) , bleeding on probing ( BOP ) , probing depth ( PD ) , gingival recession ( GR ) and clinical attachment level ( CAL ) . At the baseline examination , there were no statistically significant differences in any of the investigated parameters . Mean value of BOP decreased in the ERL group from 83 % at baseline to 31 % after 6 months ( P < 0.001 ) and in the C group from 80 % at baseline to 58 % after 6 months ( P < 0.001 ) . The difference between the two groups was statistically significant ( P < 0.001 , respectively ) . The sites treated with ERL demonstrated a mean CAL change from 5.8 + /- 1 mm at baseline to 5.1 + /- 1.1 mm ( P < 0.01 ) after 6 months . The C sites demonstrated a mean CAL change from 6.2 + /- 1.5 mm at baseline to 5.6 + /- 1.6 mm ( P < 0.001 ) after 6 months . After 6 months , the difference between the two groups was statistically not significant ( P > 0.05 ) . Within the limits of the present study , it was concluded that ( i ) at 6 months following treatment both therapies led to significant improvements of the investigated clinical parameters , and ( ii ) ERL result ed in a statistically significant higher reduction of BOP than UNLABELLED With the increased use of osseointegrated implants and with many implants functioning for a long time , the treatment of peri-implantitis has become important . Animal studies and clinical case reports have shown that the principle of guided bone regeneration can be applied to the surgical treatment of moderate to profound loss of bone around the implant , but we have found no published clinical studies . PATIENTS AND METHODS Twenty-eight patients whose ages ranged from 25 to 78 years and who had a total of 48 peri-implant defects were examined at baseline ( week 0 ) and after 18 weeks . This included the recording of bleeding on probing , pocket probing depths , and probing attachment levels at six sites for each tooth . For 2 - 18 weeks before week 0 all patients had been treated for peri-implantitis , including motivation , instruction in oral hygiene , and implant scaling with a h and plastic instrument . They were then r and omly allocated to continue with this treatment or to have in addition mechanical debridement and local application of Atridox trade mark which slowly release doxycycline . RESULTS Patients treated with Atridox trade mark showed a significantly greater gain in mean ( S.D. ) probing attachment levels than those not treated with Atridox . Only subjects treated with Atridox had a significant gain in mean bleeding on probing ( P = 0.001 ) . Application of the biodegradable sustained release device after initial periodontal treatment result ed in a significant gain in mean probing attachment levels in the Atridox trade mark group and a significant reduction in pocket probing depths . There was also a significant difference in mean probing attachment levels ( 0.6 mm ) BACKGROUND Peri-implantitis is a frequent finding in patients with dental implants . The present study compared two non-surgical mechanical debridement methods of peri-implantitis . MATERIAL AND METHODS Thirty-seven subjects ( mean age 61.5 ; S.D+/-12.4 ) , with one implant each , demonstrating peri-implantitis were r and omized , and those treated either with titanium h and -instruments or with an ultrasonic device were enrolled . Data were obtained before treatment , and at 1 , 3 , and 6 months . Parametric and non-parametric statistics were used . RESULTS Thirty-one subjects completed the study . The mean bone loss at implants in both groups was 1.5 mm ( SD + /-1.2 mm ) . No group differences for plaque or gingival indices were found at any time point . Baseline and 6-month mean probing pocket depths ( PPD ) at implants were 5.1 and 4.9 mm ( p=0.30 ) in both groups . Plaque scores at treated implants decreased from 73 % to 53 % ( p<0.01 ) . Bleeding scores also decreased ( p<0.01 ) , with no group differences . No differences in the total bacterial counts were found over time . Higher total bacterial counts were found immediately after treatment ( p<0.01 ) and at 1 week for ultrasonic-treated implants ( p<0.05 ) . CONCLUSIONS No group differences were found in the treatment outcomes . While plaque and bleeding scores improved , no effects on PPD were identified |
1,202 | 29,971,260 | Conclusions The findings of current study on 1,099 patients successfully demonstrate that the pre-procedure oral administration of Simethicone ± N-acetylcysteine improves mucosal visualization and mucosal visualization score during OGD | Background The objective of this article is to study the role of Simethicone ± N-acetylcysteine in improving the mucosal visualization during oesophago-gastro-duodenoscopy ( OGD ) . | OBJECTIVES : Little is known about missed rates of upper gastrointestinal cancer ( UGC ) in Western population s , with most data originating from Japanese centers quoting high missed rates of 23.5–25.8 % . The objective of this study was to better define missed rates of esophagogastroduodenoscopy ( EGD ) and the natural history of UGC in a Western population that underwent an initial EGD without cancer , but were subsequently diagnosed with a UGC . Our hypothesis was that a normal EGD rarely misses the detection of UGC . METHODS : This is a retrospective cohort study . A prospect ively maintained electronic data base was used to identify all patients who underwent EGD between 1990 and 2004 at the study institution . Patients in this cohort who were diagnosed with UGC before 2006 were identified through the Western Australian Cancer Registry . We defined missed cancers as those diagnosed within 1 year of EGD , possible missed cancers as those diagnosed 1–3 years after EGD , and new cancers as those diagnosed more than 3 years after EGD . This study had no interventions and was conducted at a tertiary referral center . The main outcome measurement included UGC . RESULTS : Of the 28,064 EGDs performed , UGC was diagnosed subsequent to the procedure in 116 cases ( 0.41 % ) . There were 29 missed cancers , 26 possible missed cancers , and 75 new cancers . Of the missed cancers , 11 were esophageal , 15 were gastric , and 3 were duodenal . In 69 % ( n=20 ) of the missed cancers , an abnormality was described at the site of malignancy . In 59 % ( n=17 ) of the missed cancers , the indication for EGD was an alarm symptom of dysphagia or suspected blood loss . In an univariate analysis , the presence of an alarm symptom was related to missed cancers , whereas operator experience , trainee participation , and usage of newer equipment were not . One of the main limitations of this study is that it was a retrospective review . CONCLUSIONS : UGC is rare after normal EGD , confirming the high accuracy of EGD . Institutional approval was granted for the conduct of this study A system has been constructed to evaluate the design , implementation , and analysis of r and omized control trials ( RCT ) . The degree of quadruple blinding ( the r and omization process , the physicians and patients as to therapy , and the physicians as to ongoing results ) is considered to be the most important aspect of any trial . The analytic techniques are scored with the same emphasis as is placed on the control of bias in the planning and implementation of the studies . Description of the patient and treatment material s and the measurement of various controls of quality have less weight . An index of quality of a RCT is proposed with its pros and cons . If published papers were to approximate these principles , there would be a marked improvement in the quality of r and omized control trials . Finally , a reasonable st and ard design and conduct of trials will facilitate the interpretation of those with conflicting results and help in making valid combinations of undersized trials BACKGROUND AND AIM Upper GI endoscopy ( UGE ) is essential for the diagnosis of gastrointestinal diseases . Mucus and bubbles may decrease mucosal visibility . The use of mucolytics could improve visualization . Our aim was to determine whether premedication with simethicone or simethicone plus N-acetylcysteine is effective in improving visibility during UGE . METHODS This was a r and omized , double-blinded , placebo-controlled trial with 2 control groups : no intervention and water 100 mL ( W ) ; and 3 intervention groups : simethicone 200 mg ( S ) ; S + N-acetylcysteine ( NAC ) 500 mg ( S+NAC500 ) ; and S + NAC 1000 mg ( S+NAC1000 ) . The solution was ingested 20 minutes before UGE . Gastric visibility was evaluated in 4 segments with a previously described scale . A score of less than 7 points was defined as adequate visibility ( AV ) . Water volume was used to improve visibility , and adverse reactions were evaluated as a secondary outcome . Multiple group comparison was performed using non-parametric one-way analysis of variance ( ANOVA ) . RESULTS Two hundred thirty patients were included in the study , 68 % female , mean age 49 years . The most common indication for UGE was epigastric pain/dyspepsia ( 33 % ) . AV was more frequent in the S+NAC500 and S+NAC1000 groups ( 65 % and 67 % ) compared with no intervention ( 44 % , P = .044 ) and water ( 41 % , P = .022 ) . The gastric total visibility scale ( TVS ) was significantly better in the S+NAC500 and S+NAC1000 groups compared with water ( P = .03 and P = .008 ) . Simethicone was not different from no intervention and water . S+NAC1000 required less water volume to improve visibility . No adverse reactions from the study drugs were observed . CONCLUSIONS Premedication with S+NAC500 and S+NAC1000 improves visibility during UGE . The use of simethicone did not show improvements in gastric visibility . TVS was worse in patients using water alone . ( Clinical trial registration number : NCT 01653171 . ) Background and study aim Upper endoscopy is the most common method for the diagnosis of upper gastrointestinal tract diseases . The aim of this study was to determine whether premedication with simethicone or N-acetylcysteine improves mucosal visualization during upper endoscopy . Patients and methods This was a r and omized , double-blind , placebo-controlled study of 297 patients scheduled for upper endoscopy who were premedicated 15 - 30 minutes before the procedure with : 100 mL of water ( placebo , group A ) ; water plus 100 mg simethicone ( group B ) ; water plus 100 mg simethicone plus 600 mg N-acetylcysteine ( group C ) . The primary outcome measure was the quality of mucosal visualization ( score : excellent , adequate or inadequate ) . Results The addition of simethicone ( group B ) or simethicone plus N-acetylcysteine to the water ( group C ) improved the visualization scores of endoscopies compared with water alone ( group A ) . In particular , groups B and C produced a significantly higher percentage of endoscopies with excellent visualization for the esophagus ( 91.1 % and 86.7 % , respectively , vs. 71.4 % in group A ; P < 0.001 ) and stomach ( 76.2 % and 74.5 % vs. 38.8 % in group A ; P < 0.001 ) . For the duodenum , the use of simethicone also showed an increase in the endoscopies with excellent visualization compared with water alone ( 85.1 % vs. 73.5 % ; P = 0.042 ) . There were no significant differences in scores between groups B and C or between gastric scores in patients with previous subtotal gastrectomy ( B and C vs. A ) : 60.0 % and 42.1 % vs. 28.6 % ( P = 0.14 ) . The rate of reported lesions was higher in group B but without statistical significance . Conclusions Premedication with simethicone result ed in better mucosal visibility . Such premedication might improve diagnostic yield , and should be considered for st and ard practice . Trial registered at Clinical Trials.gov ( NCT02357303 ) BACKGROUND Simethicone improves endoscopic visibility and diagnostic accuracy during colonoscopy and capsule endoscopy . Nevertheless , there have been limited data on its usefulness in esophagogastroduodenoscopy ( EGD ) . OBJECTIVE To evaluate the effectiveness of simethicone on enhancing endoscopic visibility in patients undergoing EGD . MATERIAL AND METHOD 121 patients were r and omized to take 2 ml ofeither liquid simethicone or placebo in 60 ml of water at 15 - 30 minutes before EGD . The severity scores of foam and bubbles at the esophagus , stomach and duodenum were compared . RESULTS Simethicone improved endoscopic visibility by diminishing mean cumulative ( 6.83 + /- 2.4 vs. 11.05 + /- 2.6 , p < 0.001 ) and local scores offoam and bubbles at all areas , and decreased the number and timing ofadjunctive simethicone washing ( 17.5 % vs. 74.1 % , p < 0.001 and 0 vs. 19 seconds , p < 0.001 ) . Simethicone increased endoscopist and patient satisfaction significantly without having adverse effects . CONCLUSION Using simethicone before EGD enhances endoscopic visibility , reduces adjunctive simethicone washing and increases endoscopist and patient satisfaction AIM To evaluate the efficacy of 5 mL simethicone solution in decreasing gastric foam if given at least 30 min before gastroscopy . METHODS This was a r and omized , placebo controlled , endoscopist blinded study performed at Changi General Hospital . Patients were at least 21 years old , had no prior surgical resection of the upper gastrointestinal tract , and scheduled for elective diagnostic gastroscopies . The primary outcome was the total mucosal visibility score ( TMVS ) which was evaluated using McNally score . The sample size was calculated to be 24 per group ( SD 2.4 , 80 % power , P < 0.05 , 2- sample t test ) . RESULTS Fifty-four patients were r and omised to receive either simethicone [ 1 mL liquid simethicone ( 100 mg ) in 5 mL of water ] or placebo ( 5 mL of water ) at least 30 min before their gastroscopy . Six accredited consultants conducted the gastroscopy , and the interobserver agreement of scoring TMVS was good with a Kappa statistic of 0.73 . The simethicone group had significantly better mean TMVS compared to placebo ( 5.78 ± SD 1.65 vs 8.89 ± SD 1.97 , P < 0.001 ) . The improvement was statistically significant for the duodenum and the gastric antrum , angularis , body , and fundus . Percent 51.9 of patients in the simethicone group had a TMVS of 4 ( no bubbles at all ) to 5 ( only 1 area with minimal bubbles ) , while in the placebo group 3.7 % of patients had TMVS of 4 or 5 . The number needed to treat was 2.1 to avoid a TMVS of 6 and more . The simethicone group also had a significantly shorter procedure time with less volume of additional flushes required during gastroscopy to clear away obscuring gastric foam . CONCLUSION With a premedication time of at least 30 min , 5 mL simethicone can significantly decrease gastric foam , decrease the volume of additional flushes , and shorten gastroscopy time OBJECTIVES To investigate whether a 360-degree horizontal turn after oral premedication with simethicone improves the mucosal visibility during gastroendoscopic examination , and to determine the proper time to turn over the patient . METHODS This study involved 993 patients scheduled for gastroendoscopy . Just before gastroendoscopy , after oral premedication with simethicone , patients were r and omly assigned to three groups : in Group A , patients waited for 20 min before gastroendoscopy ; in Group B , patients were separately waited for 5/10/15/20 min and were then turned 360 degrees just before gastroendoscopy ; in Group C , patients were immediately turned 360 degrees and then separately waited for 5/10/15/20 min before examination . The sum of the gastric mucosal visibility scores ( MVS ) was calculated after the examination . The MVS and proportion of images with higher visibility scores for the mucosal surface . Lower scores indicate better visibility of the mucosal surface . RESULTS In Groups B and Groups C , when waiting time more than 10 min had lower mean total MVS than Group A. The MVS of four subgroups of Group B were not different from those of Group C. CONCLUSION Oral premedication with simethicone and immediately make a body posture change ( turning over 360 degrees ) then waiting for 10min can increase the image quality during gastroendoscopy and effectively decrease the premedication time AIM : To evaluate the effects of the various methods of small bowel preparation on the quality of visualization of the small bowel and the gastrointestinal transit time of capsule endoscopy ( CE ) . METHODS : Ninety patients referred for CE were prospect ively r and omized to three equal groups according to the preparation used : ( a ) a control group , in which patients were requested to drink 1 L of clear liquids only , 12 h before the examination ; ( b ) a purgative group , in which patients were requested to ingest 1 L of a polyethylene glycol (PEG)/electrolyte solution only , 12 h before the examination ; or ( c ) a purgative combined with simethicone group ( P-S group ) , in which patients were requested to ingest 1 L of PEG , 12 h before the examination , and 300 mg of simethicone , 20 min before the examination . Effects of the different bowel preparations on the gastric transit time ( GTT ) , small bowel transit time ( SBTT ) , examination completion rate , quality of images of the entire small intestine , and cleansing of the proximal small bowel and distal ileum were evaluated . RESULTS : The number of patients with “ adequate ” cleansing of the entire small intestine was 17 in the P-S group , 12 in the purgative group , and seven in the control group ( P = 0.002 ) . The P-S group had significantly better image quality than the control group ( P = 0.001 ) . The P-S group had significantly better image quality for the proximal small bowel ( segment A [ Seg A ] ) than the control group ( P = 0.0001 ) . Both the P-S group ( P = 0.0001 ) and the purgative group ( P = 0.0002 ) had significantly better image quality for the distal ileum ( segment B [ Seg B ] ) than the control group ; the P-S group had significantly better image quality than the purgative group as well ( P = 0.0121 ) . Gastrointestinal transit time was not different among the three groups , nor was the examination completion rate . CONCLUSIONS : Purgative bowel cleansing combined with simethicone before CE improved the quality of imaging of the entire small bowel as well as the visualization of the mucosa in the proximal and distal small intestine Background and study aims : Mucosal views can be impaired by residual bubbles and mucus during gastroscopy . This study aim ed to determine whether a pre-gastroscopy drink containing simethicone and N-acetylcysteine improves mucosal visualisation . Patients and methods : We conducted a r and omized controlled trial recruiting 126 subjects undergoing routine gastroscopy . Subjects were r and omized 1:1:1 to receive : A — pre-procedure drink of water , simethicone and N-acetylcysteine ( NAC ) ; B — water alone ; or C — no preparation . Study endoscopists were blinded to group allocation . Digital images were taken at 4 locations ( lower esophagus/upper gastric body/antrum/fundus ) , and rated for mucosal visibility ( MV ) using a 4-point scale ( 1 = best , 4 = worst ) by 4 separate experienced endoscopists . The primary outcome measure was mean mucosal visibility score ( MVS ) . Secondary outcome measures were procedure duration and volume of fluid flush required to achieve adequate mucosal views . Results : Mean MVS for Group A was significantly better than for Group B ( 1.35 vs 2.11 , P < 0.001 ) and Group C ( 1.35 vs 2.21 , P < 0.001 ) . Mean flush volume required to achieve adequate mucosal views was significantly lower in Group A than Group B ( 2.0 mL vs 31.5 mL , P = 0.001 ) and Group C ( 2.0 mL vs 39.2 mL P < 0.001 ) . Procedure duration did not differ significantly between any of the 3 groups . MV scores at each of the 4 locations demonstrated significantly better mucosal visibility in Group A compared to Group B and Group C ( P < 0.0025 for all comparisons ) . Conclusions : A pre-procedure drink containing simethicone and NAC significantly improves mucosal visibility during gastroscopy and reduces the need for flushes during the procedure . Effectiveness in the lower esophagus demonstrates potential benefit in Barrett ’s oesophagus surveillance gastroscopy Background and Aim : Low-volume polyethylene glycol with ascorbic acid ( PEG-Asc ) use is reported to be as safe and effective as traditional 4-L polyethylene glycol use . However , PEG-Asc produces bubbles , which cause problems during colonoscopy . Data on the effects of using antifoaming agents such as simethicone with PEG-Asc are lacking . The aim of this CONSORT- prospect i ve , r and omized , observer-blinded , controlled trial is to compare the quality of bowel preparation and compliance between PEG-Asc users and PEG-Asc plus simethicone users . Methods : Adult out patients aged 18 to 80 years undergoing colonoscopy were recruited to the study . Two hundred sixty patients were r and omly assigned to 1 of 2 treatment arms , PEG-Asc or PEG-Asc plus simethicone . The primary outcome measure was the bowel cleansing quality using Boston bowel preparation scale and bubble scores . The secondary outcome measures were patient tolerability and doctor tolerability . Results : The simethicone group showed superior cleansing results ( 6–9 Boston scale scores : 99 % vs. 84 % , < 5 % bubble scores : 96 % vs. 49 % , P < 0.001 ) and fewer gastrointestinal symptoms ( abdominal fullness : 24 % vs. 55 % , colicky pain : 5 % vs. 24 % , P < 0.001 ) than the non-simethicone group . Moreover , endoscopist fatigue during colonoscopy was lower in the simethicone group than in the non-simethicone group ( 1.31 ± 0.75 vs. 2.97 ± 2.14 , P < 0.001 ) . Conclusion : PEG-Asc plus simethicone use was more effective and associated with better patient and endoscopist tolerance than PEG-Asc use . Therefore , this combination is recommended as one of the promising methods for bowel preparation before colonoscopy 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 Diagnostic gastroscopy provides a unique opportunity to diagnose early oesophagogastric neoplasia ; however , intraluminal mucus and bile can obscure mucosal visualization . The aim of this study was to determine whether the use of a premedication solution containing the mucolytic agent N-acetylcysteine and the surfactant simethicone improves mucosal visualization within a UK diagnostic gastroscopy service . Material s and methods A total of 75 consecutive patients were recruited from a single ( S.J. ) endoscopist ’s diagnostic gastroscopy list . They were r and omized into three treatment groups : ( a ) st and ard control = clear fluids only for 6 h , nil by mouth for 2 h ; ( b ) water control = st and ard control+100 ml sterile water ( given 20 min before gastroscopy ) ; and ( c ) solution = st and ard control+100 ml investigated solution ( 20 min before gastroscopy ) . The endoscopist was blinded to patient preparation . Inadequate mucosal visualization was defined as fluid/mucus during gastroscopy that could not be suctioned and required flushing with water . The volume of flush , the site at which it was used and the total procedure times were recorded . Results All three groups showed no statistical difference for age , sex ratio , procedure priority or indication . The mean volume of flush required to obtain clear mucosa was significantly less in the solution group compared with the other groups . The mean overall procedure time was also less in the solution group compared with the other groups . Discussion Premedication with N-acetylcysteine and simethicone markedly improves mucosal visibility during gastroscopy . It also reduces the time taken for the procedure . This low-cost and well-tolerated intervention may improve detection of early neoplasia AIM To evaluate the effectiveness of simethicone in enhancing visibility and efficacy during colonoscopy . METHODS A prospect i ve , double-blind , r and omized , placebo-controlled study was conducted . One hundred and twenty-four patients were allocated to receive 2 doses of sodium phosphate plus 240 mg of tablet simethicone or placebo as bowel preparation . Visibility was blindly assessed for the amount of air bubbles and adequacy of colon preparation . Total colonoscopic time , side effects of the medication , endoscopist and patient satisfaction were also compared . RESULTS Sodium phosphate plus simethicone , compared to sodium phosphate plus placebo , improved visibility by diminishing air bubbles ( 100.00 % vs 42.37 % , P < 0.0001 ) but simethicone failed to demonstrate improvement in adequacy of colon preparation ( 90.16 % vs 81.36 % , P = 0.17 ) . Endoscopist and patient satisfaction were increased significantly in the simethicone group . However , there was no difference in the total duration of colonoscopy and side effects of the medication . CONCLUSION The addition of simethicone is of benefit for colonoscopic bowel preparation by diminishing air bubbles , which results in enhanced visibility . Endoscopist and patient satisfaction is also increased AIM To assess the efficacy of N-acetylcysteine ( NAC ) and activated Dimethicone in improving endoscopic mucosal visibility . METHODS A total of 148 patients were r and omly allocated into four groups to receive one of the following premedications : group A : 100 mL water alone ; group B : activated Dimethicone plus water ( up to 100 mL ) ; group C : NAC plus water ( up to 100 mL ) ; and group D : activated Dimethicone and NAC plus water ( up to 100 mL ) . A single endoscopist blinded to the patients group assessed the gastric mucosal visibility scores ( range 1 - 4 ) at four sites . The sum of the scores from the four sites was considered as the total mucosal visibility score ( TMVS ) . RESULTS The patients in group B showed a significantly lower TMVS than those of groups A and C ( P < 0.001 ) . The TMVS in patients of group D was significantly lower than that of groups A and C ( P < 0.001 ) . The TMVS did not significantly differ between groups B and D ( P > 0.05 ) . The difference between TMVS of groups C and A was not significant ( P > 0.05 ) . CONCLUSION Premedication with activated Dimethicone 20 min prior to the upper endoscopy leads to the best visibility . NAC does not improve visualization by itself It has been suggested that pre-procedural oral simethicone improves visibility in upper GI tract endoscopy . We examined three-hundred-thirty patients referred for upper endoscopy who were r and omized and were required to swallow a placebo solution or one of three liquid simethicone solutions 15 min prior to the examination . These solutions contained 65 mg , 65 mg and 195 mg of drug dissolved in 90 ml , 30 ml and 90 ml of water , respectively . Patients treated with both dosages of simethicone revealed significantly less foam and bubbles in both the stomach and the duodenum compared to placebo . Only the 90 ml volume adequately cleared both locations . The reduction of examination time could be found both in patients with an intact stomach and in patients with or without gastric bile reflux , but was most striking in patients with previous gastric resection ( examination time being reduced by almost 50 % and the need of adjunctive lavage being reduced about 20 fold compared to placebo ) . In conclusion , pre-procedural oral simethicone should be routinely considered in patients with previous gastric resection . The utility of the drug is less evident in patients with normal gastric anatomy |
1,203 | 30,300,228 | The identified stimulation parameters were frequency of 20–30 Hz , pulse duration of 300–350 & mgr;s , and amplitude of the current greater than 100 mA. Neuromuscular electrical stimulation/functional electrical stimulation provides an effective rehabilitation strategy in managing spasticity . | Abstract Controversial findings about the effects of neuromuscular electrical stimulation and functional electrical stimulation in managing spasticity have been raised after spinal cord injury .
A systematic review was conducted to identify the range of the stimulation parameters that may alleviate spasticity . | The effects of long-term functional electrical stimulation (FES)-assisted walking on ankle dynamic stiffness were examined in spinal cord-injured ( SCI ) subjects with incomplete motor function loss . A parallel-cascade system identification method was used to identify intrinsic and reflex contributions to dynamic ankle stiffness at different ankle positions while subjects remained relaxed . Intrinsic stiffness dynamics were well modeled by a linear second-order model relating intrinsic torque to joint position . Reflex stiffness dynamics were accurately described by a linear third-order model relating halfwave rectified velocity to reflex torque . We examined four SCI subjects before and after long-term FES-assisted walking ( > 16 mo ) . Another SCI subject , who used FES for only five months was examined 12 mo latter to serve as a non-FES , SCI control . Reflex stiffness decreased in FES subjects by an average of 53 % following FES-assisted walking , intrinsic stiffness also dropped by 45 % . In contrast , both reflex and intrinsic stiffness increased in the non-FES , SCI control . These findings suggest that FES-assisted walking may have therapeutic effects , helping to reduce abnormal joint stiffness Among the objectives of spinal cord injury ( SCI ) rehabilitation , ( i ) prevention of bony , muscular and joint trophism and ( ii ) limitation of spastic hypertone represent important goals to be achieved . The aim of this study is to use functional electrical stimulation ( FES ) to activate pedaling on cycle-ergometer and analyse effects of this technique for a rehabilitation training in SCI persons . Five spinal cord injured subjects were recruited and underwent a two months FES-cycling training . Our results show an increase of thigh muscular area and endurance after the FES-cycling training , without any increase of spasticity . This approach , which is being vali date d on a larger pool of patients , represents a potential tool for improving the rehabilitation outcome of complete and incomplete SCI persons The goal of this research was to determine if cutaneous electrotherapy would temporarily reduce muscle spasticity . Five traumatically brain injured ( TBI ) and five spinal cord injured ( SCI ) subjects , all with clinical ly evident spasticity , received surface electrical stimulation over the tibialis anterior muscle . Using the Spasticity Measurement System , stiffness around the ankle was measured before , immediately after , and 24 hours after treatment . With stimulation , ipsilateral ankle viscoelastic stiffness immediately decreased in 9 of 10 subjects and remained significantly depressed for up to 24 hours . Contralateral ankle spasticity did not significantly change . Using the same subjects under sham conditions , no significant decrements in spasticity occurred . In a subjective survey , only SCI participants reported functionally evident spasticity reductions . Also within this subgroup , efficacy of treatment was directly proportional to the severity of pre-stimulation clonus . We conclude that ( 1 ) cutaneous electrotherapy transiently decreases both TBI and SCI related spasticity and ( 2 ) pre-stimulation clonus may function as a clinical indicator of SCI patients most likely to benefit from this process This study examined the effects of altering surface neuromuscular electrical stimulation ( SNMES ) parameters on the specific tension of the quadriceps femoris muscle . Seven able-bodied subjects had magnetic resonance images taken of both thighs prior to and immediately after four SNMES protocol s to determine the activated muscle cross-sectional area ( CSA ) . The four protocol s were : ( 1 ) research ( RES , 100 Hz , 450 μs , and amplitude set to evoke 75 % of maximal voluntary isometric torque , MVIT ) ; ( 2 ) pulse duration ( PD , 100 Hz , 150 μs , same current as in RES ) ; ( 3 ) frequency ( FREQ , 25 Hz , 450 μs , and same current as in RES ) ; ( 4 ) amplitude ( AMP , 100 Hz , 450 μs , and current set to evoke the average of the initial torques of PD and FREQ , 45 ± 9 % of MVIT ) . Reducing the amplitude of the current from 75 to 45 % of MVIT did not alter specific tension , 25 ± 8 N/cm2 , suggesting that the amplitude probably affects torque and the area of activated muscle proportionally . Shortening the pulse duration from 450 to 150 μs caused specific tension to drop from 25 ± 6 to 20 ± 6 N/cm2 ( P < 0.05 ) , indicating that pulse duration increased torque and the activated CSA disproportionally . Alternatively , reducing the frequency from 100 to 25 Hz decreased specific tension from 25 ± 6 to 17 ± 4 N/cm2 ( P < 0.05 ) , suggesting that the frequency increased torque without affecting the activated CSA . Clinicians who administer SNMES should be aware of the magnitude of adaptations to a given amplitude , pulse duration , and frequency The objective of this prospect i ve cohort study was to investigate alterations in body composition variables and spasticity following subtetanic neuromuscular electrical stimulation ( NMES ) training in an adult population with spinal cord injury ( SCI ) . Fourteen sedentary adults with SCI ( thoracic [T]4-T11 ; American Spinal Injury Association Impairment Scale A/B ; time since injury : 10.17 + /- 11.17 yr ) were recruited from the National SCI data base . Four adhesive electrodes ( 175 cm2 each ) were placed bilaterally on the proximal and distal quadriceps and hamstrings muscle groups and subtetanic contractions were elicited using a h and held NMES device . Lean body mass ( LBM ) and other body composition variables were measured using dual-energy X-ray absorptiometry . Spasticity was measured using the Spinal Cord Assessment Tool for Spastic Reflexes ( SCATs ) and visual analog scales . Verbal and written feedback was obtained to subjectively evaluate spasticity . LBM and spasticity measurements were taken before and after an 8 wk NMES training program in order to assess change . A statistically significant increase in lower-limb LBM , i.e. , muscle tissue ( p > 0.001 ) , and a reduction in SCATs ( p < 0.001 ) score , indicating reduced spasticity , was observed . Subjective responses were positive . Improvements in body composition and SCATs scores indicate that subtetanic NMES training elicits favorable responses and may have important clinical implication s for an SCI population 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 QUESTION Does functional electrical stimulation ( FES ) cycling increase urine output and decrease lower limb swelling and spasticity in people with recent spinal cord injury ? DESIGN R and omised cross-over trial . PARTICIPANTS Fourteen participants with a recent motor complete spinal cord injury were consecutively recruited from two spinal cord injury units in Sydney . INTERVENTION Participants were r and omised to an experimental phase followed by a control phase or vice versa , with a 1-week washout period in between . The experimental phase involved FES cycling four times a week for two weeks and the control phase involved st and ard rehabilitation for two weeks . Assessment s by a blinded assessor occurred at the beginning and end of each phase . Allocation was concealed and an intention-to-treat analysis was performed . OUTCOME MEASURES The primary outcome was urine output ( mL/hr ) and the secondary outcomes were lower limb circumference , and spasticity using the Ashworth Scale , and the Patient Reported Impact of Spasticity Measure ( PRISM ) . In addition , participants were asked open-ended questions to explore their perceptions about treatment effectiveness . RESULTS All participants completed the study . The mean between-group difference ( 95 % CI ) for urine output was 82mL/hr ( -35 to 199 ) . The mean between-group differences ( 95 % CI ) for lower limb swelling , spasticity ( Ashworth ) , and PRISM were -0.1 cm ( -1.5 to 1.2 ) , -1.9 points ( -4.9 to 1.2 ) and -5 points ( -13 to 2 ) , respectively . All point estimates of treatment effects favoured FES cycling . Participants reported many benefits from FES cycling . CONCLUSION There were no clear effects of FES cycling on urine output , swelling and spasticity even though all point estimates of treatment effects favoured FES cycling and participants perceived therapeutic effects . TRIAL REGISTRATION ACTRN12611000923965 Objective : Spasticity following spinal cord injury ( SCI ) can impair function and affect quality of life . This study compared the effects of transcutaneous electrical nerve stimulation ( TENS ) and functional electrical stimulation ( FES ) on lower limb spasticity in patients with SCI . Design : Double blind r and omized crossover design . Setting : Neuro-rehabilitation unit , Manipal University , India . Participants : Ten participants ( age : 39 ± 13.6 years , C1–T11 , 1–26 months post SCI ) with lower limb spasticity were enrolled in this study . Interventions : Participants were administered electrical stimulation with TENS and FES ( duration - 30 minutes ) in a cross over manner separated by 24 hours . Outcome Measures : Spasticity was measured using modified Ashworth scale ( MAS ) [ for hip abductors , knee extensors and ankle plantar flexors ] and spinal cord assessment tool for spastic reflexes ( SCATS ) . Assessment s were performed at baseline , immediately , 1 hour , 4 hours , and 24 hours post intervention . Results : A between group analysis did not show statistically significant differences between FES and TENS ( P > 0.05 ) . In the within group analyses , TENS and FES significantly reduced spasticity up to 4 hours in hip adductors and knee extensors ( P < 0.01 ) . SCATS values showed significant reductions at 1 hour ( P = 0.01 ) following TENS and 4 hours following FES ( P = 0.01 ) . Conclusion : A single session of electrical stimulation with FES and TENS appears to have similar anti-spasticity effects that last for 4 hours . The findings of this preliminary study suggest that both TENS and FES have the potential to be used as therapeutic adjuncts to relieve spasticity in the clinic . In addition , FES may have better effects on patients presenting with spastic reflexes STUDY DESIGN Experimental laboratory study . OBJECTIVES The primary purpose was to investigate the independent effects of current amplitude , pulse duration , and current frequency on muscle fatigue during neuromuscular electrical stimulation ( NMES ) . A second purpose was to determine if the ratio of the evoked torque to the activated area could explain muscle fatigue . BACKGROUND Parameters of NMES have been shown to differently affect the evoked torque and the activated area . The efficacy of NMES is limited by the rapid onset of muscle fatigue . METHODS AND MEASURES Seven healthy participants underwent 4 NMES protocol s that were r and omly applied to the knee extensor muscle group . The NMES protocol s were as follows : st and ard protocol ( Std ) , defined as 100-Hz , 450-micros pulses and amplitude set to evoke 75 % of maximal voluntary isometric torque ( MVIT ) ; short pulse duration protocol ( SP ) , defined as 100-Hz , 150-micros pulses and amplitude set to evoke 75 % of MVIT ; low-frequency protocol ( LF ) , defined as 25-Hz , 450-micros pulses and amplitude set to evoke 75 % of MVIT ; and low-amplitude protocol ( LA ) , defined as 100-Hz , 450-micros pulses and amplitude set to evoke 45 % of MVIT . The peak torque was measured at the start and at the end of the 4 protocol s , and percent fatigue was calculated . The outcomes of the 4 NMES protocol s on the initial peak torque and activated cross-sectional area were recalculated from a companion study to measure torque per active area . RESULTS Decreasing frequency from 100 to 25 Hz decreased fatigue from 76 % to 39 % . Decreasing the amplitude and pulse duration result ed in no change of muscle fatigue . Torque per active area accounted for 57 % of the variability in percent fatigue between Std and LF protocol s. CONCLUSIONS Altering the amplitude of the current and pulse duration does not appear to influence the percent fatigue in NMES . Lowering the stimulation frequency results in less fatigue , by possibly reducing the evoked torque relative to the activated muscle area OBJECTIVES To compare the effect of 3 methods of electric stimulation to reduce spasticity of the triceps surae in patients with complete spinal cord injury ( SCI ) and to investigate the carryover effect . DESIGN Placebo-controlled study with repeated measurements after the interventions . SETTING Research department affiliated with a rehabilitation hospital in the Netherl and s. PARTICIPANTS Ten patients with a complete SCI were recruited from the outpatient population of the rehabilitation hospital . All subjects had American Spinal Injury Association grade A impairment scores , except for one , who had grade C. The patients had no voluntary triceps surae contractibility . INTERVENTIONS Forty-five minutes of cyclic electric stimulation of the agonist , antagonist , or dermatome of the triceps surae or a placebo approach . MAIN OUTCOME MEASURES Outcome measures were the Modified Ashworth Scale ( MAS ) , clonus score , and the H-reflex and M wave ( H/M ) ratio . The electromyographic response to a stretch of the soleus over the whole range of motion was also determined . The magnitude and ankle angle at which the electromyographic response started were calculated . RESULTS Stimulation of the agonist provided a significant reduction in the MAS compared with the placebo approach ( P<.001 ) . There was no significant change in the H/M ratio or the electromyographic response amplitude after any of the stimulation methods , whereas stimulation of the antagonist muscle result ed in a significant reduction in the ankle angle at which the electromyographic response started , compared with the placebo approach ( P<.037 ) . CONCLUSIONS Triceps surae stimulation reduces the MAS for that specific muscle , whereas the angle at which the reflex starts changes after antagonist stimulation Complete spinal cord injury ( SCI ) results in inactivation and unloading of affected skeletal muscles . Unloading causes an increased susceptibility of muscle to contraction-induced injury . This study used magnetic resonance imaging ( MRI ) to test the hypothesis that isometric contractions would evoke greater muscle damage to the quadriceps femoris muscle ( mQF ) of SCI subjects than that of able-bodied ( AB ) controls . MR images were taken of the mQF prior to , immediately post , and 3 days post electromyostimulation ( EMS ) . EMS consisted of five sets of ten isometric contractions ( 2 s on/6 s off , 1 min between sets ) followed by another three sets of ten isometric contractions ( 1 s on/1 s off , 30 s between sets ) . Average muscle cross-sectional area ( CSA ) and the relative areas of stimulated and injured muscle were obtained from MR images by quantifying the number of pixels with an elevated T2 signal . SCI subjects had significantly greater relative area [ 90 (2)% versus 66 (4)% , P<0.05 ; mean ( SE ) ] but a lesser absolute area [ 16 ( 3 ) cm2 versus 44 ( 6 ) cm2 , P<0.05 ] of mQF stimulated than AB controls . During EMS , peak torque was reduced by 66 % and 37 % for SCI and control subjects , respectively . Three days post EMS , there was a greater relative area of stimulated mQF injured for the SCI subjects [ 25 (6)% versus 2 (1)% , P<0.05 ] . Peak torque remained decreased by 22 % on day 3 in the SCI group only . These results indicate that affected muscle years after SCI is more susceptible to contraction-induced muscle damage , as determined by MRI , compared to AB controls . They also support the contention that electrically elicited isometric contractions are sufficient to cause muscle damage after a prolonged period of inactivity We present the results and the methodology of trials using transcutaneous electrical stimulation . The aim of our work was to decrease spasticity in 44 patients with traumatic damage to the spinal cord ; 35 non-electrically stimulated spastics were used as controls . Both groups were r and omly selected from in patients in the Paraplegic Department at the Hospital Rehabilitation Centre . This electrical stimulation procedure leads to a long-lasting reduction in spasticity , an increased range of passive and active movements , the facilitation of lost functions , an improvement in breathing , an increase in pulmonary capacity , the reappearance of some neurological reflexes , and a diminution of supersensitivity to skin irritation . Blood pressure and neurogenic bladder functions were restored to normal . In addition to clinical observations , we investigated muscle force and the electromyogram ; other measurements used in the trials involved the use of a specially adapted neurological hammer , a pendulum test , spirometry , cystometry , sphincterometry and biochemical estimations |
1,204 | 30,649,569 | Conflicting evidence was found as to whether supervision of exercise improved adherence .
Adherence to prescribed exercise in SpA was poorly reported and predominately for people with AS .
The levels of adherence and factors affecting prescribed exercise in SpA remain unclear . | Adherence is a primary determinant of the effectiveness of any intervention .
Exercise is considered essential in the management of spondyloarthritis ( SpA ) ; however , the overall adherence to exercise programmes and factors affecting adherence are unknown . | Background To investigate the risk of first-time acute coronary syndrome ( ACS ) , stroke and venous thromboembolism ( VTE ) in patients with ankylosing spondylitis ( AS ) , psoriatic arthritis ( PsA ) and undifferentiated spondyloarthritis ( uSpA ) , compared to each other and to the general population ( GP ) . Methods This is a prospect i ve nationwide cohort study . Cohorts with AS ( n = 6448 ) , PsA ( n = 16,063 ) and uSpA ( n = 5190 ) patients and a GP ( n = 266,435 ) cohort , were identified 2001–2009 in the Swedish National Patient and Population registers . The follow-up began 1 January 2006 , or 6 months after the first registered spondyloarthritis ( SpA ) diagnosis thereafter , and ended at ACS/stroke/VTE event , death , emigration or 31 December 2012 . Crude and age- and sex-st and ardized incidence rates ( SIRs ) and hazard ratios ( HRs ) were calculated for incident ACS , stroke or VTE , respectively . Results St and ardized to the GP cohort , SIRs for ACS were 4.3 , 5.4 and 4.7 events per 1000 person-years at risk in the AS , PsA and uSpA cohort , respectively , compared to 3.2 in the GP cohort . SIRs for stroke were 5.4 , 5.9 and 5.7 events per 1000 person-years at risk in the AS , PsA and uSpA cohort compared to 4.7 in the GP cohort . Corresponding SIRs for VTE were 3.6 , 3.2 and 3.5 events per 1000 person-years at risk compared to 2.2 in the GP cohort . Age- and sex-adjusted HRs ( 95 % CI ) for ACS events were significantly increased in AS ( 1.54 ( 1.31–1.82 ) ) , PsA ( 1.76 ( 1.59–1.95 ) ) and uSpA ( 1.36 ( 1.05–1.76 ) ) compared to GP . Age-adjusted HRs for ACS was significantly decreased in female AS patients ( 0.59 ( 0.37–0.97 ) ) compared to female PsA patients . Age- and sex-adjusted HRs for stroke events were significantly increased in AS ( 1.25 ( 1.06–1.48 ) ) and PsA ( 1.34 ( 1.22–1.48 ) ) , and nonsignificantly increased in uSpA ( 1.16 ( 0.91–1.47 ) ) compared to GP . For VTE the age- and sex-adjusted HRs for AS , PsA and uSpA were equally and significantly increased with about 50 % compared to GP . Conclusions Patients with AS , PsA and uSpA are at increased risk for ACS and stroke events , which emphasizes the importance of identification of and intervention against cardiovascular risk factors in SpA patients . Increased alertness for VTE is warranted in patients with STUDY OBJECTIVES To underst and reasons for compliance and non-compliance with a home based exercise regimen by patients with osteoarthritis of the knee . DESIGN A qualitative study , nested within a r and omised controlled trial , examining the effectiveness of physiotherapy in reducing pain and increasing mobility in knee osteoarthritis . In the intervention arm , participants undertook a series of simple exercises and repositioning of the kneecap using tape . In depth interviews were conducted with a subset of participants in the intervention arm using open ended questions , guided by a topic schedule , to encourage patients to describe their experiences and reflect on why they did or did not comply with the physiotherapy . Interviews were audiotaped , fully transcribed and analysed thematically according to the method of constant comparison . A model explaining factors influencing compliance was developed . SETTING Patients were interviewed at home . The study was nested within a pragmatic r and omised controlled trial . PARTICIPANTS Twenty participants in the intervention arm of the r and omised trial were interviewed three months after they had completed the physiotherapy programme . Eight were interviewed again one year later . MAIN RESULTS Initial compliance was high because of loyalty to the physiotherapist . Reasoning underpinning continued compliance was more complex , involving willingness and ability to accommo date exercises within everyday life , the perceived severity of symptoms , attitudes towards arthritis and comorbidity and previous experiences of osteoarthritis . A necessary precondition for continued compliance was the perception that the physiotherapy was effective in ameliorating unpleasant symptoms . CONCLUSIONS Non-compliance with physiotherapy , as with drug therapies , is common . From the patient 's perspective , decisions about whether or not to comply are rational but often can not be predicted by therapists or research ers . Ultimately , this study suggests that health professionals need to underst and reasons for non-compliance if they are to provide supportive care and trialists should include qualitative research within trials whenever levels of compliance may have an impact on the effectiveness of the intervention Fernández-de-las-Peñas C , Alonso-Blanco C , Alguacil-Diego IM , Miangolarra-Page JC : One-year follow-up of two exercise interventions for the management of patients with ankylosing spondylitis : A r and omized controlled trial . Am J Phys Med Rehabil 2006;85:559–567 . Objective : To assess the long-term effects on functional and mobility outcomes of two exercise interventions for the management of patients with ankylosing spondylitis . Design : In an extended 12-mo follow-up of a r and omized controlled trial , 40 patients who were diagnosed with ankylosing spondylitis according to the modified criteria of New York , allocated to control or experimental groups using a r and om numbers table , and who performed their respective exercise program at least three times per month , were included in this long-term study . The control group was treated during 15 sessions with a conventional exercise regimen in ankylosing spondylitis , whereas the experimental group received 15 sessions of exercises based on the treatment of the shortened muscle chains following the guidelines described by the Global Posture Reeducation method . These patients were followed up and assessed again 1 yr after entering the study , reapplying the same vali date d indexes : BASMI ( Bath Ankylosing Spondylitis Metrology Index [ tragus to wall distance , modified Schober test , cervical rotation , lumbar side flexion , and intermalleolar distance ] ) , BASDAI ( Bath Ankylosing Spondylitis Disease Activity Index ) , and BASFI ( Bath Ankylosing Spondylitis Functional Index ) . Results : The intragroup comparison between follow-up and postintervention data showed that both groups decrease their clinical and functional measures during the follow-up period . This decrease was only significant for lumbar side flexion and intermalleolar distance measurements , being more significant in the control group ( P = 0.001 and P = 0.002 , respectively ) . Intragroup differences between follow-up and preintervention assessment s revealed that improvements in all mobility measures of the BASMI index and in the BASFI index were partially maintained at the 12-mo follow-up in the experimental group but not in the control group . The intergroup comparison ( unpaired t test analysis ) between changes on each outcome during the long-term follow-up ( post – follow-up ; and pre – follow-up ) showed no significant differences in the decrease between postintervention and follow-up data between the study groups . On the other h and , the intergroup comparison between preintervention and follow-up data revealed significant differences in almost all mobility measures of the BASMI index ( except for cervical rotation ) and in the BASFI index , in favor of the experimental group . Conclusions : An exercise regimen based on the Global Posture Reeducation method and focusing on specific strengthening and flexibility exercises of the shortened muscle chains offers promising short- and long-term results in the management of patients who have ankylosing spondylitis Background Evidence suggests people with axial spondyloarthritis ( axial SpA ) should exercise up to five times per week but lack of time , symptoms , cost and distance are barriers to regular exercise in axial SpA. Personalised exercise programmes delivered via the internet might support people with axial SpA to reach these exercise targets . The aim of this study is to investigate the effect of , and adherence to , a 12 month personalised web-based physiotherapy programme for people with axial SpA. Methods Fifty people with axial SpA will be recruited to this prospect i ve , interventional cohort study . Each participant will be assessed by a physiotherapist and an individualised exercise programme set up on www.webbasedphysio.com . Participants will be asked to complete their programme five times per week for 12 months . With the exception of adherence , data will be collected at baseline , 6 and 12 months . Discussion The primary outcome measure is adherence to the exercise programme over each four week cycle ( 20 sessions maximum per cycle ) and over the 12 months . Secondary measures include function ( BASFI ) , disease activity ( BASDAI ) , work impairment ( WPAI : SpA ) , quality of life ( ASQoL , EQ5D ) , attitude to exercise ( EMI-2 , EAQ ) , spinal mobility ( BASMI ) , physical activity and the six minute walk test . Participants will also be interviewed to explore their adherence , or otherwise , to the intervention . This study will determine the adherence and key clinical outcomes of a targeted web-based physiotherapy programme for axial SpA. This data will inform clinical practice and the development and implementation of similar programmes . Trial registration Clinical Trials.gov : NCT02666313 , 20th January Paper diaries are commonly used in health care and clinical research to assess patient experiences . There is concern that patients do not comply with diary protocol s , possibly invalidating the benefit of diary data . Compliance with paper diaries was examined with a paper diary and with an electronic diary that incorporated compliance-enhancing features . Participants were chronic pain patients and they were assigned to use either a paper diary instrumented to track diary use or an electronic diary that time-stamped entries . Participants were instructed to make three pain entries per day at predetermined times for 21 consecutive days . Primary outcome measures were reported vs actual compliance with paper diaries and actual compliance with paper diaries ( defined by comparing the written times and the electronically-recorded times of diary use ) . Actual compliance was recorded by the electronic diary . Participants su bmi tted diary cards corresponding to 90 % of assigned times ( + /-15 min ) . However , electronic records indicated that actual compliance was only 11 % , indicating a high level of faked compliance . On 32 % of all study days the paper diary binder was not opened , yet reported compliance for these days exceeded 90 % . For the electronic diary , the actual compliance rate was 94 % . In summary , participants with chronic pain enrolled in a study for research were not compliant with paper diaries but were compliant with an electronic diary with enhanced compliance features . The findings call into question the use of paper diaries and suggest that electronic diaries with compliance-enhancing features are a more effective way of collecting diary information OBJECTIVES To identify factors that are associated with older patients ' engagement in exercise in the 6 months after hospital discharge . DESIGN A prospect i ve observational study using qualitative and quantitative evaluation . SETTING Follow-up of hospital patients in their home setting after discharge from a metropolitan general hospital . PARTICIPANTS Participants ( N=343 ) were older patients ( mean age ± SD , 79.4 ± 8.5y ) discharged from medical , surgical , and rehabilitation wards and followed up for 6 months after discharge . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Self-perceived awareness and risk of falls measured at discharge with a survey that addressed elements of the Health Belief Model . Engagement and self-reported barriers to engagement in exercise measured at 6 months after discharge using a telephone survey . RESULTS Six months after discharge , 305 participants remained in the study , of whom 109 ( 35.7 % ) were engaging in a structured exercise program . Multivariable logistic regression analysis demonstrated participants were more likely to be engaging in exercise if they perceived they were at risk of serious injury from a fall ( odds ratio [ OR ] = .61 ; 95 % confidence interval [ CI ] , .48-.78 ; P<.001 ) , if exercise was recommended by the hospital physiotherapist ( OR=1.93 ; 95 % CI , 1.03 - 3.59 ; P=.04 ) , and if they lived with a partner ( OR=1.97 ; 95 % CI , 1.18 - 3.28 ; P=.009 ) . Barriers to exercise identified by 168 participants ( 55 % ) included low self-efficacy , low motivation , medical problems such as pain , and impediments to program delivery . CONCLUSIONS Older patients have low levels of engagement in exercise after hospital discharge . Research ers should design exercise programs that address identified barriers and facilitators , and provide education to enhance motivation and self-efficacy to exercise in this population OBJECTIVE To determine the extent to which measures of foot and ankle strength , range of motion , posture , and deformity are associated with performance in a battery of balance and functional ability tests in older adults . DESIGN Cross-sectional study of people over 65 years . SETTING Community . PARTICIPANTS Participants ( N=305 ; age range , 65 - 93y ) recruited for a r and omized trial investigating the efficacy of a podiatry intervention to prevent falls . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Clinical measures of foot and ankle strength ( using h and -held dynamometry ) , range of motion , posture , and deformity , and a battery of balance tests ( postural sway , maximum balance range , lateral stability , coordinated stability ) and functional ability tests ( alternate step test , sit-to-st and , timed 6-m walk ) . RESULTS Most ( 67/88 ) of the correlations between the foot and ankle tests and performance on the balance and functional tests were statistically significant . Hierarchic linear regression analysis identified hallux plantar flexion strength and ankle inversion-eversion range of motion to be the most consistent significant and independent predictors of balance and functional test performance , explaining up to 25 % of the variance in the test scores . CONCLUSIONS Foot and ankle characteristics , particularly plantar flexor strength of the hallux and ankle inversion-eversion range of motion , are important determinants of balance and functional ability in older people . Further research is required to establish whether intervention programs that include strengthening and stretching exercises for the foot and ankle may achieve improvements in balance and functional ability and reduce the risk of falls in older people PURPOSE Group physical therapy in patients with ankylosing spondylitis was studied to determine whether beneficial effects persisted after cessation of the intervention . METHODS After a 9-month period of supervised group physical therapy , 68 patients were r and omized for another 9 months to unsupervised daily exercises at home ( discontinuation group ) or continuation of weekly sessions of supervised group physical therapy ( continuation group ) . Endpoints were spinal mobility ( thoraco-lumbar flexion and extension , chest expansion , cervical rotation ) , fitness ( maximum work capacity ) , functioning ( Sickness Impact Profile ( SIP ) , Health Assessment Question naire for the Spondylarthropathies [ HAQ-S ] , Functional Index [ FI ] ) , and patient 's global health assessment on a visual analogue scale . RESULTS Time for exercises at home was significantly higher in the continuation than in the discontinuation group ( mean duration 1.9 versus 1.2 hr per week , P < 0.05 ) . The continuation group improved in global health ( mean improvement 1.6 ; 32 % ) and in SIP score . Scores for thoraco-lumbar mobility and HAQ-S did not change very much , whereas chest expansion , cervical rotation , fitness , and FI deteriorated . The average attendance for group therapy sessions was 62 % . The discontinuation group improved only marginally ( 0.2 ; 4 % ) in global health , whereas all other endpoints decreased . Only for global health and HAQ-S were the differences statistically significant in favor of the continuation group . CONCLUSIONS Global health and functioning are sustained or even improved further if group physical therapy is continued . Spinal mobility decreased slightly in both groups Arthritis is a common chronic disease causing pain and progressive disability to millions of people . The purpose of the study was to examine the effectiveness of group patient education for people with one form of arthritis , ankylosing spondylitis ( AS ) , in terms of change in : arthritis self-efficacy ; psychological well-being ; physical well-being ; and home exercise activities . The Self-Management Course-Ankylosing Spondylitis ( SMC-AS ) demonstrated positive effects on arthritis self-efficacy and psychological well-being at 6-month follow-up . Analysis of change over time in the intervention group showed improvements in depression , self-efficacy and severity at 3 weeks , with trends towards continued improvement evident at 6 months . In contrast , the positive effects on range and frequency of home exercise activities at 3 weeks were not maintained at 6 months . In conclusion , the effectiveness of short , intensive patient education courses was demonstrated . However , the need for strategies to sustain improvements in exercise behaviour need to be explored OBJECTIVE Home based self-care is essential for successful management of ankylosing spondylitis ( AS ) . We design ed an intervention package aim ed at promoting self-care and regular longterm exercise and evaluated its effect on outcome . METHOD Members of our data base ( n = 4569 ) were r and omly selected and r and omized to an intervention group ( IG ) or a followup control group ( CG ) . The intervention consisted of an exercise/information video , exercise progress chart , patient education booklet , and AS exercise reminder stickers . The outcome measures were function ( BASFI ) , disease activity ( BASDAI ) , global well being ( BAS-G ) , exercise self-efficacy ( ESE ) , arthritis self-efficacy ( SES ) , and quantity of AS mobility/aerobic exercise assessed at baseline and 6 months . RESULTS Of the 200 subjects , 155 completed the study ( 75 IG and 80 CG ) . Baseline analysis showed no differences between the CG and the IG . At 6 months , analysis revealed no statistically significant between-group differences for the BASFI , BASDAI , and BAS-G. although the p value of 0.08 for function approached significance . Self-efficacy for exercise showed a significant improvement in the IG ( p = 0.045 ) . There were no between-group differences for the SES pain and other symptoms subscales . Finally , there was a significant increase in self-reported AS mobility ( p < 0.001 ) and aerobic exercise ( p < 0.05 ) in the IG . CONCLUSION An exercise intervention package design ed to promote self-management in AS ( 1 ) significantly improves self-efficacy for exercise ; ( 2 ) significantly improves self-reported levels of exercise ; ( 3 ) reveals a trend for improvement in function ( BASFI ) PURPOSE To study the effects of adding supervised group physical therapy to unsupervised individualized therapy in ankylosing spondylitis . METHODS One hundred forty-four patients were r and omized to exercises at home , or the same plus weekly group physical therapy for 9 months . Endpoints were spinal mobility , fitness ( maximum work capacity by ergometry ) , functioning ( Sickness Impact Profile , Health Assessment Question naire for the Spondylarthropathies , and Functional Index ) , and patient 's global assessment of change on a 10-cm visual analogue scale . RESULTS Thoracolumbar flexion and extension increased by an average of 0.5 cm ( 9 % ) after home exercises , and by 0.9 cm ( 16 % ) after group therapy . Maximum load in ergometry decreased by 2 W ( 1 % ) after home exercises , but increased by 7 W ( 4 % ) after group therapy . Global assessment improved by 0.3 ( 6 % ) after home exercises , and by 1.7 ( 34 % ) after group therapy . These three differences were statistically significant . There were no significant differences in chest expansion , cervical rotation , or the self- assessment s of functioning . CONCLUSIONS Group physical therapy proved superior to individualized therapy in improving thoracolumbar mobility and fitness , and had an important effect on global health reported by the patients More than half of all patients with psoriatic arthritis ( PsA ) exhibit progressive erosive arthritis , associated with severe functional impairment and psychosocial disability . Biologics have been suggested to be more effective in inducing minimal disease activity " ( MDA ) than disease-modifying antirheumatic drugs ( DMARDs ) . Behavioral patient education appears to be more effective in encouraging patients to increase their physical activity ( PA ) levels . The aim of the study was to evaluate the benefits of home-based exercises program on disease activity and quality of life in MDA-PsA patients treated with an anti-tumor necrosis factor ( TNF ) and DMARD therapy . We observed a self-reported adherence rate to home-based exercise of 76.6 % and data showed the impact of the exercise program on self-reported health and mental assessment . A positive relationship between patient and therapist is crucial , influencing the quality of the performance , the emotional support , and increasing motivation in PsA patients |
1,205 | 31,603,895 | Box plots also showed no apparent differences in intensity reduction between the two treatment strategies .
/ SIGNIFICANCE The results of this meta- analysis do not support the hypothesis that community-wide treatment is more effective than targeted treatment at reducing schistosomiasis infections in children . | BACKGROUND Schistosomiasis is a widespread public health concern in the poorest regions of the world .
The principal control strategy is regular praziquantel administration to school-aged children in endemic areas .
With calls for the elimination of schistosomiasis as a public health problem , exp and ing praziquantel delivery to all community members has been advocated .
This systematic review and meta- analysis compares the impact of community-wide and child-targeted praziquantel distribution on schistosomiasis prevalence and intensity in school-aged children . | A field trial was conducted in the Gezira , Sudan , to evaluate the acceptability and efficacy of praziquantel , a new schistosomicide . In one Arab village 350 patients with Schistosoma mansoni were r and omly assigned to two treatment groups and given 1 X 40 mg kg-1 ( Group A ) or 2 X 20 mg kg-1 given four to six hours apart ( Group B ) . In two small settlements ( camps ) 2 km distant from the Arab village 38 patients with S. mansoni and 43 with concurrent S. mansoni and S. haematobium infections were given 1 X 40 mg kg-1 . Side effects were mild and limited to the first 24 hours after treatment . The main complaints were abdominal pain , diarrhoea , urticaria and /or vomiting and were most common in the camp residents ( 79 % ) with 60 % of Group A and 45 % of Group B having one or more side effects . One month after treatment ' cure ' rates were : Camps 63 % , Group A 84 % and Group B 96 % , and the reduction in egg output was over 95 % . After 12 months re-infection was greater in the camps . As there was no significant difference in the egg output reduction between the two treatment regimes , praziquantel is recommended for mass chemotherapy in Gezira at the logistically simpler regimen of 1 X 40 mg kg-1 Background The Schistosomiasis Consortium for Operational Research and Evaluation ( SCORE ) has launched several large-scale trials to determine the best strategies for gaining and sustaining control of schistosomiasis and transitioning toward elimination . In Côte d’Ivoire , a 5-year cluster-r and omized trial is being implemented in 75 schools to sustain the control of schistosomiasis mansoni . We report Schistosoma mansoni infection levels in children one year after the initial school-based treatment ( SBT ) with praziquantel and compare with baseline results to determine the effect of the intervention . Methodology The baseline cross-sectional survey was conducted in late 2011/early 2012 and the first follow-up in May 2013 . Three consecutive stool sample s were collected from 9- to 12-year-old children in 75 schools at baseline and 50 schools at follow-up . Stool sample s were subjected to duplicate Kato-Katz thick smears . Directly observed treatment ( DOT ) coverage of the SBT was assessed and the prevalence and intensity of S. mansoni infection compared between baseline and follow-up . Principal Findings The S. mansoni prevalence in the 75 schools surveyed at baseline was 22.1 % ( 95 % confidence interval ( CI ) : 19.5–24.4 % ) . The DOT coverage was 84.2 % . In the 50 schools surveyed at baseline and one year after treatment , the overall prevalence of S. mansoni infection decreased significantly from 19.7 % ( 95 % CI : 18.5–20.8 % ) to 12.8 % ( 95 % CI : 11.9–13.8 % ) , while the arithmetic mean S. mansoni eggs per gram of stool ( EPG ) among infected children slightly increased from 92.2 EPG ( 95 % CI : 79.2–105.3 EPG ) to 109.3 EPG ( 95 % CI : 82.7–135.9 EPG ) . In two of the 50 schools , the prevalence increased significantly , despite a DOT coverage of > 75 % . Conclusions / Significance One year after the initial SBT , the S. mansoni prevalence had decreased . Despite this positive trend , an increase was observed in some schools . Moreover , the infection intensity among S. mansoni-infected children was slightly higher at the 1-year follow-up compared to the baseline situation . Our results emphasize the heterogeneity of transmission dynamics and provide a benchmark for the future yearly follow-up surveys of this multi-year SCORE intervention study Integrated control strategies are important for sustainable control of schistosomiasis and soil-transmitted helminthiasis , despite their challenges for their effective implementation . With the support of Good Neighbors International in collaboration with National Institute of Medical Research , Mwanza , Tanzania , integrated control applying mass drug administration ( MDA ) , health education using PHAST , and improved safe water supply has been implemented on Kome Isl and over 5 years for controlling schistosomiasis and soil-transmitted helminths ( STHs ) . Baseline surveys for schistosomiasis and STHs was conducted before implementation of any integrated control strategies , followed by 4 cross-sectional follow-up surveys on r and omly selected sample s of schoolchildren and adults in 10 primary schools and 8 villages , respectively , on Kome isl and s. Those follow-up surveys were conducted for impact evaluation after introduction of control strategies interventions in the study area . Five rounds of MDA have been implemented from 2009 along with PHAST and improved water supply with pumped wells as other control strategies for complementing MDA . A remarkable steady decline of schistosomiasis and STHs was observed from 2009 to 2012 with significant trends in their prevalence decline , and thereafter infection rate has remained at a low sustainable control . By the third follow-up survey in 2012 , Schistosoma mansoni infection prevalence was reduced by 90.5 % and hookworm by 93.3 % among schoolchildren while in adults the corresponding reduction was 83.2 % and 56.9 % , respectively . Integrated control strategies have successfully reduced S. mansoni and STH infection status to a lower level . This study further suggests that monitoring and evaluation is a crucial component of any large-scale STH and schistosomiasis intervention Background In Mozambique , schistosomiasis is highly endemic across the whole country . The Schistosomiasis Consortium for Operational Research and Evaluation ( SCORE ) coordinates a five-year study that has been implemented in various African countries , including Mozambique . The overall goal of SCORE was to better underst and how to best apply preventive chemotherapy with praziquantel ( PZQ ) for schistosomiasis control by evaluating the impact of alternative treatment approaches . Methods This was a cluster-r and omised trial that compared the impact of different treatment strategies in study areas with prevalence among school children of ≥21 % S. haematobium infection by urine dipstick . Each village was r and omly allocated to one of six possible combinations of community-wide treatment ( CWT ) , school-based treatment ( SBT ) , and /or drug holidays over a period of four years , followed by final data collection in the fifth year . The most intense intervention arm involved four years of CWT , while the least intensive arm involved two years of SBT followed by two consecutive years of PZQ holiday . Each study arm included 25 villages r and omly assigned to one of the six treatment arms . The primary outcome of interest was change in prevalence and intensity of S. haematobium among 100 children aged 9-to-12-years that were sample d each year in every village . In addition to children aged 9-to-12 years , 100 children aged 5–8 years in their first-year of school and 50 adults ( aged 20–55 years ) were tested in the first and final fifth year of the study . Prevalence and intensity of S. haematobium infection was evaluated by two filtrations , each of 10mL , from a single urine specimen . Principal findings In total , data was collected from 81,167 individuals across 149 villages in ten districts of Cabo Delgado province , Northern Mozambique . Overall PZQ treatment result ed in a significant reduction in the prevalence of S. haematobium infection from Year 1 to Year 5 , where the average prevalence went from 60.5 % to 38.8 % , across all age groups and treatment arms . The proportion of those heavily infected also reduced from 17.6 % to 11.9 % over five years . There was a significantly higher likelihood of males being infected than females at baseline , but no significant difference between the sexes in their response to treatment . The only significant response based on a study arm was seen in both the 9-to-12-year-old and first-year cross sections , where two consecutive treatment holidays result ed in a significantly higher final prevalence of S. haematobium than no treatment holidays . When the arms were grouped together , four rounds of treatment ( regardless of whether it was CWT or SBT ) , however , did result in a significantly greater reduction in S. haematobium prevalence than two rounds of treatment ( i.e. with two intermittent or consecutive holiday years ) over a five-year period . Conclusions Although PC was successful in reducing the burden of active infection , even among those heavily infected , annual CWT did not have a significantly greater impact on disease prevalence or intensity than less intense treatment arms . This may be due to extremely high starting prevalence and intensity in the study area , with frequent exposure to reinfection , or related to challenges in achieving high treatment coverage More frequent treatment had a greater impact on prevalence and intensity of infection when arms were grouped by number of treatments , however , cost efficiency was greater in arms only receiving two treatments . Finally , a significant reduction in prevalence of S. haematobium was seen in adults even in the SBT arms implying the rate of transmission in the community had been decreased , even where only school children have been treated , which has significant logistical and cost-saving implication s for a national control programme in justifying CWT A parasitological , clinical and ultrasonographic longitudinal study was undertaken in 1993 in a focus hyperendemic for Schistosoma mansoni infection in the central highl and s of Madagascar . All the inhabitants were systematic ally treated with praziquantel . A complete examination and treatment were repeated each year . Among the 289 villagers who underwent the complete 3 years ' follow up , 65.9 % excreted eggs at the initial survey and the mean egg count of infected individuals was 202 eggs/g . In 1996 , the prevalence of infection was 19.3 % with a mean egg count of 27 eggs/g and , among inhabitants aged > 44 years , only one was found to be infected . The proportion of individuals complaining of bloody stool decreased from 24.9 % in 1993 to 8.4 % in 1996 . Compared to the initial clinical examination , the age-adjusted prevalence of splenomegaly was significantly lower in 1996 , but remained high : 62 % in the 10 - 14 years age group and 59 % in individuals aged > 24 years . Ultrasonographic examination after 3 years of praziquantel therapy showed a marked decrease of the overall prevalence of schistosomal hepatic fibrosis , from 28 % in 1993 to 10.3 % in 1996 . This improvement had already been achieved during the second year of follow-up for most subjects . Usually , the reversal of morbidity affected individuals classified as stage 1 at the beginning of the study . Stage 3 was not observed in the last 2 surveys . One patient 's ascites disappeared during the follow-up , associated with a significant reversal of periportal fibrosis . Our results indicate that repeated praziquantel therapy can lead to improvement of liver morbidity and the prevention of the development of schistosomal hepatic fibrosis , even in an old-established hyperendemic focus OBJECTIVE In the course of performing systematic review s on the prevalence of low back and neck pain , we required a tool to assess the risk of study bias . Our objectives were to ( 1 ) modify an existing checklist and ( 2 ) test the final tool for interrater agreement . STUDY DESIGN AND SETTING The final tool consists of 10 items addressing four domains of bias plus a summary risk of bias assessment . Two research ers tested the interrater agreement of the tool by independently assessing 54 r and omly selected studies . Interrater agreement overall and for each individual item was assessed using the proportion of agreement and Kappa statistic . RESULTS Raters found the tool easy to use , and there was high interrater agreement : overall agreement was 91 % and the Kappa statistic was 0.82 ( 95 % confidence interval : 0.76 , 0.86 ) . Agreement was almost perfect for the individual items on the tool and moderate for the summary assessment . CONCLUSION We have addressed a research gap by modifying and testing a tool to assess risk of study bias . Further research may be useful for assessing the applicability of the tool across different conditions BACKGROUND In sub-Saharan Africa , 112 million people are infected with Schistosoma haematobium , with the most intense infections in children 5 - 15 years old . METHODS We describe a longitudinal epidemiological study that evaluates the relationship between S. haematobium infection and associated morbidity in children before and after the large-scale administration of praziquantel for schistosomiasis and albendazole for soil-transmitted helminths . RESULTS At baseline , higher intensities of S. haematobium infection were observed in children with anemia and /or severe microhematuria , but there was no apparent association between the risk of undernutrition and intensity of S. haematobium infection . Significant reductions in the prevalence and intensity of S. haematobium infection 1 year after treatment were , however , observed . Children who benefited the most from anthelmintic treatment in terms of increased hemoglobin concentrations were those who had anemia at baseline and those with highly positive microhematuria scores at baseline . CONCLUSIONS This study suggests that even a single round of mass chemotherapy can have a substantial impact on S. haematobium infection and its associated morbidity in children Although it is established that the treatment by praziquantel reduces the urinary lesions due to Schistosoma haematobium , the frequency of mass treatment necessary to maintain a low morbidity level remains poorly known . The objective of this work was to study the impact over three years of a single praziquantel mass treatment on schistosomiasis morbidity in two different systems of disease transmission in Niger . The study was performed in 2 villages hyperendemic for schistosomiasis in the South-West of Niger presenting respectively 2 different systems of schistosomiasis transmission : Koutoukalé-Zéno ( K Zéno ) , located close to an irrigated area of the Niger River Valley where the transmission is permanent , and Téguey located along a temporary pond where the transmission is seasonal . After the initial evaluation ( 1994 ) , we carried out a survey 3 years later ( 1997 ) except in K. Zéno where an intermediate evaluation was performed 10 months after the initial survey ( 1995 ) . Approximately 300 r and omised people have been examined as follows : macroscopic examination of urine and reagent sticks for macro- and micro-haematuria , filtration and microscopic examination of urine for Schistosoma eggs , and ultrasound scan of the urinary tract for morbidity . The therapeutic coverage has reached 69.9 % in K. Zéno and 78.2 % in Téguey . The prevalence of infestation decreased from 74.1 % to 56.4 % in K. Zéno ( p < 0.001 ) and from 65.3 % to 30.4 % in Téguey ( p < 0.001 ) at the end of the 3 years . The prevalence of heavy infestation ( eggs > or = 50 ) went in the same time from 9.9 % to 12.8 % ( p = 0.3 ) in K. Zéno and from 9.1 % to 3.3 % in Téguey ( p = 0.01 ) . Using ultrasound scan , the prevalence of the bladder lesions reached its previous level in both villages . However the prevalence of hydronephrosis decreased from 21.1 % to 3.9 % in K. éno ( p < 0.001 ) and from 12.6 % to 4.2 % in Téguey ( p < 0.001 ) . Three years after the single mass treatment , the morbidity did not reach the initial level . The effectiveness of the treatment is better in the pond system where the transmission is seasonal . The lesions of the upper tract decreased more slowly than the bladder lesions , but a long time after the treatment . The re-infestation induced the re-appearance of the bladder lesions sooner than the lesions of the upper tract . The periodicity of the treatment should be variable according to the transmission system . It should occur every 2 years in irrigated areas and could be delayed ( 3 years ) in temporary ponds . The control was beneficial in the pond system and induced a significant reduction of the severe lesions Background Mass drug administration ( MDA ) using praziquantel is the WHO-recommended approach for control of schistosomiasis . However , few studies have compared the impact of different schedules of MDA on the result ant infection levels . We wished to evaluate whether annual MDA was more effective than less frequent treatments for reducing community-level prevalence and intensity of Schistosoma mansoni infections . Methods We performed a cluster r and omized trial ( IS RCT N 14849830 ) of 3 different MDA frequencies over a 5 year period in 75 villages with moderate ( 10%-24 % ) initial prevalence of S. mansoni in school children in western Kenya . Praziquantel was distributed by school teachers to students either annually , the first 2 years , or every other year over a 4 year period . Prevalence and intensity of infection were measured by stool examination in 9–12 year old students using the Kato-Katz method at baseline , each treatment year , and for the final evaluation at year 5 . S. mansoni prevalence and intensity were also measured in first year students at baseline and year 5 . Results Twenty-five schools were r and omly assigned to each arm . S. mansoni prevalence and infection intensity in 9–12 year old students significantly decreased within each arm from baseline to year 5 but there were no differences between arms . There were no differences in infection levels in first year students either within or between arms . Conclusions Strategies employing 2 or 4 rounds of MDA had a similar impact in schools with moderate initial prevalence , suggesting that schistosomiasis control can be sustained by school-based MDA , even if provided only every other year This study compared the effect of the community-directed treatment ( ComDT ) approach and the school-based treatment approach on the prevalence and intensity of schistosomiasis and soil-transmitted helminthiasis ( STH ) among schoolchildren . Following a parasitological survey in a r and omly selected sample of 1140 schoolchildren , school-age children in 10 study villages received one dose of praziquantel ( 40 mg/kg body weight ) against schistosomiasis and one dose of albendazole ( 400 mg ) against STH . Five of these villages implemented the ComDT approach and received treatment by community drug distributors , while school teachers administered treatment in five other villages using the school-based approach . At 12 months follow-up , the prevalence of Schistosoma mansoni and Trichuris trichiura infections were similar between the ComDT and the school-based approaches when examined in r and omly selected schoolchildren ( 10.1 vs. 9.4 % , P=0.66 and 0.8 vs. 1.4 % , P=0.37 ) . However , the prevalence of S. haematobium and hookworm infections were significantly lower in the ComDT approach villages compared to the school-based approach villages ( 10.6 vs. 16.3 % , P=0.005 and 2.9 vs. 5.8 % , P=0.01 , respectively ) . The results showed that the ComDT approach is at least as effective as the school-based approach in reducing prevalence and intensity of schistosomiasis and STH among schoolchildren The paper describes the endemic situation of schistosomiasis japonica in Fanhu village , Poyang Lake region , China and the effect of the strategy of combining annual mass chemotherapy with health education on schistosomiasis control in the community . The results showed that the prevalence of infection with schistosome reduced form 26.0 % in 1992 to 10.7 % in 1994 , the intensity of infection in residents decreased from 1.92 in 1992 to 0.55 in 1994 and the condition of hepatomegaly , splenomegaly and liver fibrosis also improved after chemotherapy in the individuals in the case prospect i ve study . Moreover , the future strategies of schistosomiasis control in this area have been suggested according to the transmission of schistosomiasis in the lake region and the effect of anti-schistosomiasis control indifferent population Abstract . Annual school-based mass drug administration with praziquantel has been widely implemented to control schistosomiasis , but other treatment strategies could have a different impact . The aim of this study was to investigate the impact of six different treatment strategies on Schistosoma mansoni infection in a cluster-r and omized controlled trial in schoolchildren , in a high transmission area of the Mwanza Region , Tanzania . A total of 150 villages were r and omized into six arms with 25 villages in each arm . In each village , approximately 100 schoolchildren aged 9–12 years were r and omly selected each year and investigated for S. mansoni prevalence and intensity based on three consecutive stool sample s using the duplicate Kato – Katz technique . Four years of community-wide treatment ( CWT ) was the most intensive treatment strategy , whereas 2 years of school-based treatment ( SBT ) combined with 2 years without treatment ( holiday ) was the least intensive treatment . The remaining strategies constituted different combinations of CWT , SBT , and holiday years . Baseline results on S. mansoni infection were obtained from 14,620 schoolchildren from 148 villages , and mean prevalence and mean intensity among infected were 48.6–60.6 % and 130.5–229.8 eggs per gram , respectively . Over the years , mean prevalence and mean intensities declined in all arms , but when comparing year 5 mean prevalence and mean intensity , there were no statistically significant differences between treatment arms . Thus , measured in a r and om selection of schoolchildren aged 9–12 years , four times CWT was not superior to four times SBT , while 2 years of treatment holiday combined with 2 years of SBT had the same impact as 4 years of SBT Background Soil-transmitted helminth ( STH ) and schistosome infections are among the most prevalent neglected tropical diseases ( NTDs ) in the world . School-aged children are particularly vulnerable to these chronic infections that can impair growth , nutritional status and cognitive ability . Mass drug administration ( MDA ) delivered either once or twice annually is a safe and effective approach recommended by the World Health Organization ( WHO ) to reduce worm burden . In 2012 , Kenya began a national school-based deworming programme ( NSBDP ) aim ed at reducing infection and associated morbidity . The change in prevalence and intensity of these infections was monitored over five years ( 2012–2017 ) . Here , we present the changes in STH and schistosome infections between baseline and endline assessment s , as well as explore the yearly patterns of infection reductions . Methods We used series of pre- and post-MDA intervention , repeat cross-sectional surveys in a representative , stratified , two-stage sample of schools in 16 counties of Kenya . The programme consisted of two tiers of monitoring ; a national baseline , midterm and endline surveys consisting of 200 schools , and pre- and post-MDA surveys conducted yearly consisting of 60 schools . Stool and urine sample s were collected from r and omly selected school children and examined for STH and schistosome infections using Kato-Katz and urine filtration techniques respectively . Results Overall , 32.3 % , 16.4 % and 13.5 % of the children were infected with any STH species during baseline , midterm and endline assessment , respectively , with a relative reduction of 58.2 % over the five-year period . The overall prevalence of S. mansoni was 2.1 % , 1.5 % and 1.7 % and of S. haematobium was 14.8 % , 6.8 % and 2.4 % , respectively , for baseline , midterm and endline surveys . We observed inter-region and inter-county heterogeneity variation in the infection levels . Conclusions The analysis provided robust assessment of the programme and outlined the current prevalence , mean intensity and re-infection pattern of these infections . Our findings will allow the Government of Kenya to make informed decisions on the strategy to control and eliminate these NTDs . Our results suggest that complimentary interventions may have to be introduced to sustain the chemotherapeutic gains of MDA and accelerate attainment of elimination of these NTDs as a public health problem in Kenya |
1,206 | 28,342,907 | The use of active placebos was clustered in specific research setting s and did not appear to reflect consistently the side effect profile of the experimental intervention , for example , selective serotonin reuptake inhibitors were compared with active placebos in pain trials but not in depression trials .
The main argument for active placebo was to reduce risk of unblinding ; the main argument against was the risk of unintended therapeutic effect .
Pharmacological active placebo control interventions are rarely used in r and omized clinical trials , but they constitute a method ological tool which merits serious consideration .
We suggest that active placebos are used more often in trials of drugs with noticeable side effects , especially in situations where the expected therapeutic effects are modest and the risk of bias due to unblinding is high | OBJECTIVES Active placebos are control interventions that mimic the side effects of the experimental interventions in r and omized trials and are sometimes used to reduce the risk of unblinding .
We wanted to assess how often r and omized clinical drug trials use active placebo control groups ; to provide a catalog , and a characterization , of such trials ; and to analyze method ological arguments for and against the use of active placebo . | An open field trial was conducted comparing desipramine and an active placebo in separate population s of chronic cocaine and phencyclidine ( PCP ) abusers , who discontinued their abuse . Subjects who received desipramine showed a decrease in depressive symptoms after a 20 - 40 day period regardless of whether they abused PCP or cocaine BACKGROUND The N-methyl-d-aspartate receptor antagonist ketamine has rapid antidepressant effects in major depression . Psychotomimetic symptoms , dissociation and hemodynamic changes are known side effects of ketamine , but it is unclear if these side effects relate to its antidepressant efficacy . METHODS Data from 108 treatment-resistant in patients meeting criteria for major depressive disorder and bipolar disorder who received a single subanesthetic ketamine infusion were analyzed . Pearson correlations were performed to examine potential associations between rapid changes in dissociation and psychotomimesis with the Clinician-Administered Dissociative States Scale ( CADSS ) and Brief Psychiatric Rating Scale ( BPRS ) , respectively , manic symptoms with Young Mania Rating Scale ( YMRS ) , and vital sign changes , with percent change in the 17-item Hamilton Depression Rating scale ( HDRS ) at 40 and 230min and Days 1 and 7 . RESULTS Pearson correlations showed significant association between increased CADSS score at 40min and percent improvement with ketamine in HDRS at 230min ( r=-0.35 , p=0.007 ) and Day 7 ( r=-0.41 , p=0.01 ) . Changes in YMRS or BPRS Positive Symptom score at 40min were not significantly correlated with percent HDRS improvement at any time point with ketamine . Changes in systolic blood pressure , diastolic blood pressure , and pulse were also not significantly related to HDRS change . LIMITATIONS Secondary data analysis , combined diagnostic groups , potential unblinding . CONCLUSIONS Among the examined mediators of ketamine׳s antidepressant response , only dissociative side effects predicted a more robust and sustained antidepressant . Prospect i ve , mechanistic investigations are critically needed to underst and why intra-infusion dissociation correlates with a more robust antidepressant efficacy of ketamine BACKGROUND Although significant evidence suggests that diminished monoamine function is associated with clinical depression , catecholamine or indoleamine depletion alone has not been associated with significant mood changes in unmedicated depressed subjects or never-depressed control subjects . This study assesses the integrated role of these monoamine systems in depressed patients . METHODS Unmedicated depressed subjects underwent a 2-week , double-blind , r and om-ordered crossover study consisting of the following active and control conditions respectively : indoleamine ( via tryptophan depletion ) plus catecholamine ( via alpha-methyl-paratyrosine administration ) depletion and , separately , indoleamine plus sham ( via diphenhydramine administration ) catecholamine depletion . Ten subjects completed both conditions ; two subjects were withdrawn after active testing and one after control testing . RESULTS Mean Hamilton Depression Rating Scale ( HDRS ) scores decreased progressively throughout the study days ( baseline 26.7 points + /- 1.7 SEM and termination 20.0 + /- 2.4 , active depletion ; baseline 26.1 points + /- 2.3 SEM and termination 23.2 + /- 2.6 , control testing ) but did not differ between groups . Only three patients demonstrated 20 % or greater increases from baseline HDRS at any point during the observation days . CONCLUSIONS Overall , results show that simultaneous disruptions of indoleamine and catecholamine function do not exacerbate symptoms in unmedicated depressed subjects , thus lending further support to the notion that monoamines regulate mood in actively depressed patients via indirect mechanisms A sample of placebo-controlled tricyclic antidepressant studies was examined retrospectively to determine whether there was any difference in the relative efficacy of the tricyclic when it was compared against an inert placebo as against an active ( atropine ) placebo with anticholinergic side effects . Fewer studies showed a significant difference between atropine placebo and drug than between inert placebo and drug . The possibilities that atropine has a specific antidepressant effect , or that side effects amplify placebo responses are considered BACKGROUND Although hypotheses about the therapeutic mechanism of action of light therapy have focused on serotonergic mechanisms , the potential role , if any , of catecholaminergic pathways has not been fully explored . METHODS Sixteen patients with seasonal affective disorder who had responded to a st and ard regimen of daily 10000-lux light therapy were enrolled in a double-blind , placebo-controlled , r and omized crossover study . We compared the effects of tryptophan depletion with catecholamine depletion and sham depletion . Ingestion of a tryptophan-free amino acid beverage plus amino acid capsules was used to deplete tryptophan . Administration of the tyrosine hydroxylase inhibitor alpha-methyl-paratyrosine was used to deplete catecholamines . Diphenhydramine hydrochloride was used as an active placebo during sham depletion . The effects of these interventions were evaluated with measures of depression , plasma tryptophan levels , and plasma catecholamine metabolites . RESULTS Tryptophan depletion significantly decreased plasma total and free tryptophan levels . Catecholamine depletion significantly decreased plasma 3-methoxy-4-hydroxyphenylethyleneglycol and homovanillic acid levels . Both tryptophan depletion and catecholamine depletion , compared with sham depletion , induced a robust increase ( P<.001 , repeated- measures analysis of variance ) in depressive symptoms as measured with the Hamilton Depression Rating Scale , Seasonal Affective Disorder Version . CONCLUSIONS The beneficial effects of light therapy in the treatment of seasonal affective disorder are reversed by both tryptophan depletion and catecholamine depletion . These findings confirm previous work showing that serotonin plays an important role in the mechanism of action of light therapy and provide new evidence that brain catecholaminergic systems may also be involved OBJECTIVE Ketamine , a glutamate N-methyl-d-aspartate ( NMDA ) receptor antagonist , has shown rapid antidepressant effects , but small study groups and inadequate control conditions in prior studies have precluded a definitive conclusion . The authors evaluated the rapid antidepressant efficacy of ketamine in a large group of patients with treatment-resistant major depression . METHOD This was a two-site , parallel-arm , r and omized controlled trial of a single infusion of ketamine compared to an active placebo control condition , the anesthetic midazolam . Patients with treatment-resistant major depression experiencing a major depressive episode were r and omly assigned under double-blind conditions to receive a single intravenous infusion of ketamine or midazolam in a 2:1 ratio ( N=73 ) . The primary outcome was change in depression severity 24 hours after drug administration , as assessed by the Montgomery-Åsberg Depression Rating Scale ( MADRS ) . RESULTS The ketamine group had greater improvement in the MADRS score than the midazolam group 24 hours after treatment . After adjustment for baseline scores and site , the MADRS score was lower in the ketamine group than in the midazolam group by 7.95 points ( 95 % confidence interval [ CI ] , 3.20 to 12.71 ) . The likelihood of response at 24 hours was greater with ketamine than with midazolam ( odds ratio , 2.18 ; 95 % CI , 1.21 to 4.14 ) , with response rates of 64 % and 28 % , respectively . CONCLUSIONS Ketamine demonstrated rapid antidepressant effects in an optimized study design , further supporting NMDA receptor modulation as a novel mechanism for accelerated improvement in severe and chronic forms of depression . More information on response durability and safety is required before implementation in clinical practice The mechanism of action of electroconvulsive therapy ( ECT ) in treating major depression is unknown . We studied two c and i date mechanisms through inhibiting simultaneously the synthesis of noradrenaline and serotonin in patients immediately after successful treatment with ECT using a r and omised , placebo-controlled , double-blind crossover design . There were no significant changes in depression scores under any experimental conditions , or between the amine-depleted and placebo groups despite reductions of 61 % in serum homovanillic acid , 47 % in 3-methoxy-4-hydroxyenylethyleneglycol , and 89 % in serum tryptophan . Catecholamine and serotonin availability may not be necessary for maintaining the initial antidepressant response to ECT Psychopharmacological studies usually attempt to eliminate " nonspecific " influences on outcome by double-blind design s. In a r and omized , double-blind comparison of alprazolam , imipramine , and placebo , the great majority of panic disorder patients ( N = 59 ) and their physicians were able to rate accurately whether active drug or placebo had been given . Moreover , physicians could distinguish between the two types of active drugs . Inasmuch as correct rating was possible halfway through treatment , concerns about the internal validity of the double-blind strategy arise TOC summary The 50 % likelihood of receiving a drug or placebo in clinical trials modifies the outcome , an effect strongly modulated if minor onset sensations are associated with drug intake . ABSTRACT The knowledge of having only a 50 % chance of receiving an active drug can result in reduced efficacy in blinded r and omized clinical trials ( RCTs ) compared to clinical practice ( reduced external validity ) . Moreover , minor onset sensations associated with the drug ( but not with an inert placebo ) can further challenge the attribution of group differences to drug‐specific efficacy ( internal validity ) . We used a r and omized experimental study with inert placebos ( inert substance ) vs active placebos ( inducing minor sensations ) , and different instructions about group allocation ( probability of receiving drug : 0 % , 50 % , 100 % ) . One hundred forty‐four healthy volunteers were informed that a new application method for a well‐known painkiller would be tested . Pain thresholds were assessed before and after receiving nasal spray . Half of the nasal sprays were inert placebos ( sesame oil ) , while the other half were active placebos inducing prickling nasal sensations ( sesame oil with 0.014 % capsaicin ) . The major outcome was pain threshold after placebo application . A substantial expectation effect was found for the inert placebo condition , with participants who believed they had received an active drug reporting the highest pain thresholds . Active placebos show substantial differences to passive placebos in the 50 % chance group . Therefore , patient expectations are significantly different in placebo‐controlled clinical trials ( 50 % chance ) vs clinical practice ( 100 % chance ) . Moreover , minor drug onset sensations can challenge internal validity . Effect sizes for these mechanisms are medium , and can substantially compete with specific drug effects . For clinical trials , new study design s are needed that better control for these effects As part of a study of drug treatment of aggressive behavior to be reported separately , we have evaluated the double‐blind procedure in a recently completed comparison of the efficacy of lithium carbonate versus placebo in modifying aggressive behavior in nonpsychotic incarcerated delinquents . We conclude that the side effects of lithium carbonate are sufficient to reveal the medication to most subjects receiving it . Thus , while the study staff could not identify lithium‐receivers at better than chance levels , and while subjects who received placebo could not identify their medication at better than chance levels , subjects who received lithium could accurately identify it . On a weekly symptom check list there was no difference between lithium and placebo groups on average lithium target symptoms reported during 4‐week pre‐ and postmedication control periods ; however , lithium‐receivers reported significantly more target symptoms every week medication was administered . Of 16 subjects who quit the study , 14 had received lithium and nearly all of those who gave reasons for quitting specified side effects , most often nausea . The method ological problems of using lithium in a double‐blind design might be overcome by employing a “ discontinuation ” design , or , speculatively , a double‐blind , cross‐over design utilizing an “ active placebo ” Objective : Although antidepressants are widely prescribed as analgesics in chronic back pain , their clinical pharmacology is not well established . Norepinephrine transporter blockade seems to be essential for analgesia , but optimal concentrations are unknown . Fixed-dose studies of serotonin reuptake inhibitors are generally negative , but such studies can not be interpreted clearly because efficacy might be detected if concentration-response relationships were known . We evaluated ( 1 ) the feasibility of conducting a controlled-concentration study of a norepinephrine ( desipramine ) and a serotonin reuptake ( fluoxetine ) inhibitor and ( 2 ) the relationship between achieved concentrations and analgesic response . Methods : This single-center , 12-week , double-blind , prospect i ve , controlled-concentration study r and omized 121 chronic back pain patients without major depression to active placebo ( benztropine mesylate ) or to predetermined low , medium , or high concentrations of desipramine ( targets were 50 , 110 , and 150 ng/mL , respectively ) or fluoxetine ( targets were 100 , 200 , and 400 ng/mL , respectively ) . Of these , 83 completed the trial : 38 withdrew primarily due to side effects . Results : Manipulation check revealed significant overlap of assigned and achieved concentrations related to drug intolerability . Completers ' analysis of achieved concentrations revealed reduction in pain intensity was significantly greater for low-concentration desipramine ( < 60 ng/mL , mean Descriptor Differential Scale [ DDS ] , 4.5 ) compared with placebo ( DDS 6.2 ) , higher concentrations of desipramine ( > 60 ng/mL , DDS 7.9 ) , and all concentrations of fluoxetine ( P < 0.05 , DDS 7.1 ) . Significant improvement in everyday function mirrored findings for pain intensity . Conclusions : Preliminary evidence for a low-concentration " therapeutic window " for noradrenergic analgesia may warrant additional study Serotonergic reuptake inhibitors have been the primary medications for treatment of obsessivecompulsive disorder ( OCD ) ; however , other serotonergic and α2-adrenergic medications also have been reported to reduce obsessive-compulsive symptoms . In this study , we compare three medications with reported efficacy in OCD to a control medication , diphenhydramine , a medication without theoretical or demonstrated treatment benefit . The three active medications were clomipramine , a serotonergic reuptake inhibitor ; clonazepam , a benezodiazepine with putative serotonergic properties ; and clonidine , an α2-adrenergic agonist . Twenty-eight subjects with DSM-III-R diagnosis of OCD rotated through 6-week trials of each of the four medications in a r and omized , double-blind , multiple crossover protocol . Clomipramine and clonazepam were both effective relative to the control medication in reducing OCD symptoms . There was a significant cross-response between these two medications ; however 40 % of subjects failing clomipramine trials had a clinical ly significant response to clonazepam treatment . The control medication , diphenhydramine , itself produced a significant decrement in symptoms , whereas clonidine was ineffective in reducing OCD symptoms . Clonazepam improvement was unrelated to changes in anxiety and occurred early in treatment . Clonazepam was significantly more effective than the other medications during the first 3 weeks of treatment . The results confirm the efficacy of clomipramine in the treatment of OCD and suggest that clonazepam might be a useful alternative treatment for patients with this disorder . ( J Clin Psychopharmacol 1992 ; 12:420–430 Noradrenergic and dopaminergic mechanisms have been proposed for the pathophysiology of seasonal affective disorder ( SAD ) . We investigated the effects of catecholamine depletion using α-methyl-para-tyrosine ( AMPT ) , an inhibitor of tyrosine hydroxylase , in patients with SAD in natural summer remission . Nine drug-free patients with SAD by DSM-IV criteria , in summer remission for at least eight weeks , completed a double-blind , crossover study . Behavioral ratings and serum HVA and MHPG levels were obtained for 3-day sessions during which patients took AMPT or an active control drug , diphenhydramine . The active AMPT session significantly reduced serum levels of HVA and MHPG compared with the control diphenhydramine session . The AMPT session result ed in higher depression ratings with all nine patients having significant clinical relapse , compared with two patients during the diphenhydramine session . All patients returned to baseline scores after drug discontinuation . Catecholamine depletion results in significant clinical relapse in patients with SAD in the untreated , summer-remitted state . AMPT-induced depressive relapse may be a trait marker for SAD , and /or brain catecholamines may play a direct role in the pathogenesis of SAD Δ9-Tetrahydrocannabinol ( Δ9-THC ) , the most prominent psychoactive cannabinoid in Cannabis sativa L. ( marijuana ) , has been reported to have properties of appetite stimulation , promotion of weight gain , and antiemetic efficacy in selected patient population s. In this 4-week , double-blind , crossover study , 11 female patients with primary anorexia nervosa ( PAN ) were evaluated on Δ9-THC and on an active placebo , diazepam . All patients participated in a st and ardized behavior modification treatment program . The following data were obtained : ( 1 ) daily weight , ( 2 ) daily caloric intake , and ( 3 ) weekly psychiatric assessment s. The two groups were comparable on all measures at baseline except for two items on the behavioral rating scales . The only significant differences found between the changes over time on Δ9-THC versus diazepam were more pathology on Δ9-THC for somatization , interpersonal sensitivity , and sleep disturbance . Three patients experienced severe dysphoric reactions consisting of paranoid ideation and feelings of loss of control during Δ9-THC administration . One week after the study ended , each subject was given the highest dose level of Δ8-THC achieved in the study , and periodic blood sample s were obtained coincident with self-rated “ subjective high ” assessment s and pulse measurements . Quantitative analyses of these sample s indicated peak times of 1 to 5 hours postdose for Δ9- THC and for its primary active metabolite , 11-hydroxy-THC , which generally coincided with peak times for “ subjective high ” and pulse rate . The results of this clinical investigation suggest that Δ9-THC is not efficacious , in short-term administration , in the treatment of primary anorexia nervosa and is associated with significant psychic disturbance in some PAN patients BACKGROUND Although state-related alterations in catecholamine function have been well-described in depressed subjects , enduring abnormalities have been less reliably identified . In our study , medication-free subjects with fully remitted major depression underwent a paradigm of catecholamine depletion , via use of the tyrosine hydroxylase inhibitor alpha-methylparatyrosine . METHOD Subjects underwent 2 sets of testing conditions in a double-blind , r and om-ordered , crossover design , approximately 1 week apart . They underwent active catecholamine depletion ( via oral administration of 5 g alpha-methylparatyrosine ) or sedation-controlled , sham catecholamine depletion ( via oral administration of 250 mg diphenhydramine hydrochloride ) , during a 2-day observation . Serial mood ratings and blood sample s were obtained . RESULTS Fourteen subjects completed the active testing condition ; 13 completed sham testing . Subjects experienced marked , transient increases in core depressive and anxiety symptoms , as demonstrated by a mean 21-point increase on Hamilton Depression Rating Scale scores . Furthermore , 10 ( 71 % ) of 14 subjects fulfilled relapse criteria during active testing , whereas 1 ( 8 % ) of 13 subjects did so during sham testing . The severity of the depressive reaction correlated with baseline plasma cortisol levels ( r = 0.59 ; P = .04 ) . CONCLUSIONS Euthymic , medication-free subjects with a history of major depression demonstrate significant depressive symptoms when undergoing testing with alpha-methylparatyrosine . This depressive reaction may represent a reliable marker for a history of depression . Further work is needed to clarify the significance of this finding To underst and the relative efficacy of noradrenergic and serotonergic antidepressants as analgesics in chronic back pain without depression , we conducted a r and omized , double-blind , placebo-control head-to-head comparison of maprotiline ( a norepinephrine reuptake blocker ) and paroxetine ( a serotonin reuptake blocker ) in 103 patients with chronic low back pain . Of these 74 completed the trial ; of the 29 who did not complete , 19 were withdrawn because of adverse effects . The intervention consisted of an 8-week course of maprotiline ( up to 150 mg daily ) or paroxetine ( up to 30 mg daily ) or an active placebo , diphenhydramine hydrochloride ( up to 37.5 mg daily ) . Patients were excluded for current major depression . Reduction in pain intensity ( Descriptor Differential Scale scores ) was significantly greater for study completers r and omized to maprotiline compared to placebo ( P=0.023 ) , and to paroxetine ( P=0.013 ) , with a reduction of pain by 45 % compared to 27 % on placebo and 26 % on paroxetine . These results suggest that at st and ard dosages noradrenergic agents may provide more effective analgesia in back pain than do selective serotonergic reuptake inhibitors Brain catecholamines can be rapidly reduced by inhibiting their synthesis with alpha-methyl-para-tyrosine ( AMPT ) . In order to assess the role of catecholamines in antidepressant action AMPT challenges were administered in a double-blind , placebo-controlled , crossover fashion to 14 depressed patients having maintained a therapeutic antidepressant response for > or = 2 weeks ( 3 desipramine , 2 mazindol , 5 fluoxetine , 4 sertraline ) . Each patient participated in two challenges one week apart . Each challenge included a baseline , two days of either AMPT or diphenhydramine ( active placebo ) , and a followup . Antidepressant drugs were continued throughout testing . The 3 desipramine- and 2 mazindol-responders had a rapid increase in depression score during AMPT but not placebo ( diphenhydramine ) challenge whereas only 1 of 9 selective serotonin reuptake inhibitor (SSRI)-treated patients did . The implication of this is that the antidepressant response to desipramine may be more acutely dependent on brain catecholamine content than the response to SSRIs . In the context of our previous work with tryptophan depletion , these results suggest that the neurobiological mechanisms underlying the antidepressant responses to different drugs involve alterations in the functioning of different neurotransmitter systems and reinforce the importance of changes in both the serotonin and catecholamine systems for successful antidepressant responses Patients and physicians correctly identified medication assignments in 70 % of the cases in a double-blind trial of an appetite suppressant . The breach of the double-blind design may have had therapeutic consequences ; correct identification was associated with favorable outcome . These findings suggest that requirements for describing the side effects of medications to patients before they give informed consent may help them guess which medication they receive and thus may influence the integrity of double-blind studies and the results of controLled trials BACKGROUND We determined whether blindness in a double-blind r and omized controlled trial of alprazolam and exposure therapies in patients with panic disorder and agoraphobia was maintained in assessors and patients , what were the factors related to " unblinding , " and whether unblinding was associated with clinical outcome . METHOD In 129 patients with panic disorder and agoraphobia who were r and omized to alprazolam-exposure , placebo-exposure , alprazolam-relaxation , or placebo-relaxation conditions , blindness was tested at the end of treatment by the independent assessors ' and patients ' classification of the treatment condition . RESULTS Assessors ' classifications were correct in 82 % of the alprazolam group and 78 % of the placebo group ; corresponding figures for patients ' classifications were 73 % and 70 % , respectively . Factors associated with unblinding included drug side effects but not assessors ' ratings of treatment outcome . CONCLUSION Judgment of the validity of the outcome of a r and omized controlled trial is easier if the report notes not only the use of a double-blindness procedure but also details how blind the raters remained and how any unblinding affected their ratings of clinical outcome BACKGROUND Sub-anesthetic ketamine infusions may benefit a variety of psychiatric disorders , including addiction . Though ketamine engenders transient alterations in consciousness , it is not known whether these alterations influence efficacy . This analysis evaluates the mystical-type effects of ketamine , which may have therapeutic potential according to prior research , and assesses whether these effects mediate improvements in dependence-related deficits , 24h postinfusion . METHODS Eight cocaine dependent individuals completed this double-blind , r and omized , inpatient study . Three counter-balanced infusions separated by 48h were received : lorazepam ( 2 mg ) and two doses of ketamine ( 0.41mg/kg and 0.71mg/kg , with the former dose always preceding the latter ) . Infusions were followed within 15min by measures of dissociation ( Clinician Administered Dissociative Symptoms Scale : CADSS ) and mystical-type effects ( adapted from Hood 's Mysticism Scale : HMS ) . At baseline and 24h postinfusion , participants underwent assessment s of motivation to stop cocaine ( University of Rhode Isl and Change Assessment ) and cue-induced craving ( by visual analogue scale for cocaine craving during cue exposure ) . RESULTS Ketamine led to significantly greater acute mystical-type effects ( by HMS ) relative to the active control lorazepam ; ketamine 0.71mg/kg was associated with significantly higher HMS scores than was the 0.41mg/kg dose . HMS score , but not CADSS score , was found to mediate the effect of ketamine on motivation to quit cocaine 24h postinfusion . CONCLUSIONS These findings suggest that psychological mechanisms may be involved in some of the anti-addiction benefits result ing from ketamine . Future research can evaluate whether the psychoactive effects of ketamine influence improvements in larger sample |
1,207 | 25,098,197 | Deep surgical site infection ( Peto odds ratio = 7.08 ; 95 % confidence interval : 1.39 , 35.99 ; P = .02 ; I(2 ) = 0 % ) , superficial surgical site infection , fixation failure , and reoperation to remove metalwork were more common after early ankle movement compared to immobilization .
The effects of early movement after ankle surgery on short-term functional outcomes are unclear , but there is no observable difference in the longer term .
There is a small reduction in risk of postoperative thromboembolism with early ankle movement .
Current evidence suggests that deep and superficial surgical site infections , fixation failure , and the need to remove metalwork are more common after early ankle movement . | OBJECTIVES To compare early ankle movement versus ankle immobilization after surgery for ankle fracture on clinical and patient-reported outcomes .
BACKGROUND A significant proportion of patients undergoing surgery for ankle fracture experience postoperative complications and delayed return to function .
The risks and benefits of movement of the ankle in the first 6 weeks after surgery are not known , and clinical practice varies widely . | In a prospect i ve , r and omized study , 30 patients were evaluated after ankle fracture treated by means of open reduction and internal fixation . The patients were r and omized to either postoperative immobilization in a plaster cast for 6 weeks or early mobilization ( 1–2 weeks after surgery ) in an ankle brace . Both regimens allowed weightbearing . Evaluation after 10 weeks and after 12 months included clinical assessment and isokinetic muscle strength measurements . Patients with impaired ankle function , as shown by means of an ankle score at 12 months , were followed for 3 years . At 10 weeks , impaired muscle torque and restricted range of motion was found on the affected side . This impairment was significantly less in the brace group . At 12 months , range of motion of the ankle and subtalar joints was restored , but dorsiflexion was still better in the brace group . Score values from a functional score did not correlate with muscle strength The effect of early mobilization and unrestricted weight bearing on final ankle motion in 51 operatively stabilized ankle fractures was prospect ively investigated . Patients were treated with an ankle-foot orthosis ( AFO ) or a cast . Full weight bearing was unrestricted in both groups . Thirty-two fractures received an AFO and 19 received a cast . The follow-up period ranged from 2.3 to 66 months , with a median of eight months . At the final follow-up examination , the motion in the AFO-treated group was not functionally different from that of the cast-treated group . However , 72 % of the patients treated in an AFO compared with 37 % of patients treated in a cast had ankle dorsiflexion greater than 15 degrees ( p = 0.014 ) . No complications were directly related to the AFO . No loss of reduction occurred in any patient . The results of this series indicate that early motion of a fractured ankle treated operatively does not affect ankle motion . Early motion was not associated with increased morbidity or loss of reduction We r and omised prospect ively 60 consecutive patients who were undergoing internal fixation of similar fractures of the ankle into two groups , one of which was treated by immobilisation in a below-knee cast and the other by a functional brace with early movement . All were instructed to avoid weight-bearing on the affected side . They were seen at 6 , 12 , 26 and 52 weeks . The functional rating scale of Mazur et al was used to evaluate the patients at each follow-up and we recorded the time of return to work . After one year the patients completed the SF-36 question naire . By then 55 patients remained in the study , 28 ( mean age 45.5 years ) in group 1 and 27 ( mean age 39.5 years ) in group 2 . Those in group 2 had higher functional scores at each follow-up but only at six weeks was this difference significant ( p = 0.02 ) . They also had higher mean SF-36 scores , but this difference was significant only for two of the eight aspects investigated . For patients gainfully employed , not on workers ' compensation , the mean time from surgery to return to work was 53.3 days for group 2 and 106.5 days for group 1 ; this difference was significant ( p = 0.01 ) . No patient developed a problem with the wound or had loss of fixation . Our findings support the use of a functional brace and early movement after surgery for fractures of the ankle Fifty-three patients with dislocated lateral malleolar fractures were r and omly selected after operation for either active ankle movement and weight bearing in an orthosis or no ankle movement but weight bearing in a walking cast . At follow-up examinations after three , six , and 18 months , no differences were found between the groups except for a better linear analogue scale result at three months for the orthosis group . Active ankle movements do not improve the rehabilitation of surgically treated lateral malleolar fractures In a prospect i ve , r and omised study , 27 patients with internally fixed ankle fractures were treated post-operatively for a period of six weeks by application of either a new dynamic vacuum orthosis with permitted mobilisation to 10 ° –0 ° –10 ° at the ankle joint or a synthetic cast . Full weight bearing was allowed in both groups after two weeks . The cast group was prescribed four weeks of physiotherapy following six weeks of immobilisation . After ten weeks , the Olerud and Mol and er score showed a significant difference in favour of the orthosis . Early functional outcomes were significantly better for this group after six weeks and ten weeks . Patients in the orthosis group who were in formal employment returned to work 24 days earlier than those in the control group . Treatment of the orthosis patients took up three to four times less working time for the medical personnel . A saving of 38 euros on directly ascertainable costs could be evaluated . Rehabilitation of ankle fractures with a dynamic vacuum orthosis leads to better early functional results and greater patient satisfaction . The orthosis fulfils the conditions for early return to work . Treatment with an orthosis not only reduces working time for medical personnel but economises on expenditure for treatment and rehabilitation . RésuméUne étude r and omisée a été réalisée chez 27 patients présentant une fracture de la cheville et traités sur une période de six semaines soit par une orthèse dynamique permettant une mobilisation de 10 ° dans chaque secteur soit par une immobilisation plâtrée . Une marche avec appui complet a été autorisée dans les deux groupes , après 15 jours . Le groupe des patients plâtrés a bénéficié de 4 semaines de rééducation après six semaines d’immobilisation . Après 10 semaines , le score d’Olerud et de Mol and er montre une différence significative dans les résultats en faveur de l’orthèse . En effet , le devenir fonctionnel de ces patients a été de façon significative bien meilleur pour ce groupe après six semaines et après dix semaines . Ces patients sont retournés au travail 24 jours plus tôt que dans le groupe contrôle . Le traitement par orthèse permet d’économiser 38 euros et du temps médical . La rééducation de la fracture des chevilles grâce à l’orthèse dynamique permet un résultat fonctionnel excellent et relativement rapide . Cette orthèse met les patients dans de bonnes conditions pour un retour précoce à l’emploi , ce traitement permet également d’économiser le travail des médecins et permet également de faire des économies sur le temps de rééducation BACKGROUND AND PURPOSE The goal of this investigation was to study the recovery of ankle plantar-flexor peak torque , fatigue resistance , and functional ability ( stair climbing , walking ) following cast immobilization in patients with ankle fractures . SUBJECTS The participants were 10 patients who underwent open reduction-internal fixation and 8 weeks of cast immobilization following a fracture of the ankle mortise and 10 age- and sex-matched , noninjured comparison subjects . METHODS Plantar-flexor torque and fatigue resistance were measured at 1 , 5 , and 10 weeks of rehabilitation using an isokinetic dynamometer . Ankle plantar-flexor peak torque and fatigue resistance were correlated to timed ambulation , timed stair climbing , and unilateral heel-rises . RESULTS Following immobilization , plantar-flexor peak torque was decreased at all angular speeds and positions . The decrease in peak torque was associated with an increase in fatigue resistance . With rehabilitation , ankle plantar-flexor torque and fatigue resistance normalized . Regression analysis revealed a strong relationship between plantar-flexor peak torque and functional measures . By 10 weeks post-immobilization , peak torque , fatigue resistance , and all measures of functional performance had returned to control levels . CONCLUSION AND DISCUSSION The decrease in muscle performance , functional ability , and fatigue resistance induced by 8 weeks of cast immobilization can be reversed with 10 weeks of supervised physical therapy . In addition , this study demonstrated that ankle-plantar flexor torque is a good predictor of stair-climbing and walking performance in patients with ankle fractures Background : The aim of operative treatment for ankle fractures is to allow early movement after internal fixation . The hypothesis of this study was that early mobilization would improve functional recovery in patients after surgery for ankle fractures . Methods : In a prospect i ve r and omized controlled study , 66 consecutive patients with ankle fractures that required open reduction and internal fixation ( ORIF ) were assigned to one of two postoperative regimens : immobilization in a nonweightbearing below-knee cast or early mobilization in a removable cast . Four patients were excluded from the study , leaving 62 for review . Results : Patients who had early mobilization in a removable cast had higher functional scores ( Olerud-Mol and er and AOFAS ) at 9 and 12 weeks postoperatively . They also returned to work earlier ( 67 days ) compared with those treated in nonweightbearing below-knee cast ( 95 days ) , p < 0.05 . There was no statistical difference in Quality of Life ( SF-36 Question naire ) at 6 months between the two groups . We had an approximately 10 % postoperative infection trend ( one superficial and two deep ) in the early mobilization group . Conclusion : Despite the overall short-term benefit of early mobilization , we had three patients in the early mobilization group who had wound complications . Both the surgeon and patient should be aware of the higher risk of wound complications associated with this treatment , and thus the accelerated rehabilitation protocol should be individualized In a prospect i ve r and omized trial the early functional results after immobilisation in a cast were compared to those after using a vacuum stabilizing system . The vacuum stabilizing system Vacoped offers equivalent stability compared to a plaster cast . In contrast to the cast the Vacoped can be removed for body care and physical therapy . Additionally the range of motion for dorsal flexion/extention in the upper ankle joint can be adjusted . From 9/1996 to 7/1997 there were 40 patients included in the study with an operated ankle fracture as monotrauma . Six weeks postoperatively the patients with cast treatment showed significantly higher functional deficits for the upper ankle joint ( 20 % ) , the lower ankle joint ( 40 % ) and muscle atrophy ( 2.1 cm side difference ) than the group with the vacuum stabilizing system ( upper ankle joint 15 % , lower ankle joint 25 % , 1.4 cm muscle atrophy ) . Five patients out of the group with the vacuum system were already at work three weeks postoperatively . Three months postoperatively the functional results for both groups were approximating . The vacuum stabilizing system Vacoped offers better early functional results than conventional cast treatment after osteo synthesis of ankle fractures . Because of the increased patient comfort and the early ability for physical therapy the vacuum stabilizing system is preferable to cast treatment Fifty-six patients who had a displaced fracture of the ankle necessitating surgical fixation were r and omly assigned to one of three postoperative treatment regimens : no plaster cast or weight-bearing , and active exercises of the ankle ; a non-weight-bearing plaster cast ; or a plaster walking cast for the first six postoperative weeks . At follow-up with a duration of as much as two years , there were no consistent differences in the clinical results between the three groups . The time lost from work and the proportion of excellent and good clinical results were also uninfluenced by the postoperative regimen . No adverse effects could be detected as a result of the patient 's having walked before the syndesmosis screw had been removed . It was concluded that none of the three postoperative regimens has any advantage over the others in a patient who has a stable osteo synthesis of a fracture of the ankle Background : Controversy continues with regard to the optimal postoperative care after open reduction and internal fixation of an ankle fracture . The hypothesis of this study was that postoperative treatment of an ankle fracture with a brace that allows active and passive range-of-motion exercises would improve the functional recovery of patients compared with that after conventional treatment with a cast . Thus , the purpose of this prospect i ve , r and omized study was to compare the long-term subjective , objective , and functional outcome after conventional treatment with a cast and that after use of functional bracing in the first six weeks following internal fixation of an ankle fracture . Methods : One hundred patients with an unstable and /or displaced Weber type-A or B ankle fracture were treated operatively and then were r and omly allocated to two groups : immobilization in a below-the-knee cast ( fifty patients ) or early mobilization in a functional ankle brace ( fifty patients ) for the first six postoperative weeks . The follow-up examinations , which consisted of subjective and objective ( clinical , radiographic , and functional ) evaluations , were performed at two , six , twelve , and fifty-two weeks and at two years postoperatively . Results : There were no perioperative complications in either study group , but eight patients who were managed with a cast and thirty-three patients who were managed with a brace had postoperative complications , which were mainly related to wound-healing . Two patients in the group treated with a cast had deep-vein thrombosis . All fractures healed well in both groups . The difference between the two groups with respect to the complication rate was significant ( p = 0.0005 ) . No significant differences between the study groups were observed in the final subjective or objective ( clinical ) evaluation . At the two-year follow-up examination , the average score ( and st and ard deviation ) according to the ankle-rating scale of Kaikkonen et al. was 85 ± 9 points for the group treated with a cast and 83 ± 10 points for the group treated with a brace , and the average ankle score according to the system of Olerud and Mol and er was 87 ± 8 points and 87 ± 9 points , respectively . Conclusions : The long-term functional outcome after postoperative treatment of an ankle fracture with a cast and that after use of a functional brace are similar . Although early mobilization with use of a functional ankle brace may have some theoretical beneficial effects , the risk of postoperative wound complications associated with this treatment approach is considerably increased compared with that after conventional cast treatment . Thus , the postoperative protocol of treatment with a functional brace requires refinement before it can be generally advocated for use after operative treatment of an ankle fracture . Level of Evidence : Therapeutic study , Level I-1b ( r and omized controlled trial [ no significant difference but narrow confidence intervals ] ) . See Intructions to Authors for a complete description of levels of evidence In a r and omised prospect i ve controlled trial of 52 patients aged 16 to 65 we compared early non-weightbearing ankle mobilisation with ankle immobilisation following surgical treatment of bimalleolar ankle fractures . At 3 months there was no significant difference between the two groups in the range of ankle movements or pain . There was however a significant difference in the gait pattern with a higher proportion of cases in the early ankle mobilisation group having a symmetrical gait ( P = 0.0001 ) Forty-three patients with stable internal fixation of fresh ankle fractures were treated at r and om with a plaster cast for 6 weeks without weight bearing or were only immobilized for 3 days , after which active movements were encouraged . The two groups were followed for a year . Only at 6 weeks were there significant differences between the groups Sixty-one active-duty military personnel with operatively treated ankle fractures were r and omized into two postoperative immobilization regimens : Group I -- six weeks short-leg cast , nonweight-bearing ; Group II -- six weeks removable orthosis , nonweightbearing . Group I began physical therapy at six weeks postoperatively , and Group II began physical therapy within the first postoperative week . Objective measurements of swelling , strength , range of motion , and functional tests were examined . Subjective scores of pain , function , cosmesis , and motion were recorded . Patients in Group II ( early mobilization ) had significantly better subjective scores at three and six months postoperatively ; however , time to return to duty was not significantly different . Objective tests of swelling , strength , range of motion , and functional tests were not significantly different at three months postoperatively for either group . Early mobilization in a removable orthosis , while not objective ly altering the postoperative course , provides a safe , preferable method of treatment in the reliable and cooperative patient The CONSORT statement is used worldwide to improve the reporting of r and omised controlled trials . Kenneth Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . To encourage dissemination of the CONSORT 2010 Statement , this article is freely accessible on bmj.com and will also be published in the Lancet , Obstetrics and Gynecology , PLoS Medicine , Annals of Internal Medicine , Open Medicine , Journal of Clinical Epidemiology , BMC Medicine , and Trials |
1,208 | 32,163,581 | Changes in cognition and academic skills were not examined in any studies .
CONCLUSIONS BSIs improve sleep , at least in the short-term , in children with NNDDs .
Benefits may extend to functional improvements in behavior . | STUDY OBJECTIVES Sleep disturbances are common and associated with negative functional and health consequences in children with neurological and neurodevelopmental disorders ( NNDDs ) , and represent an important potential target for behavioral interventions .
This systematic review examined the efficacy of behavioral sleep interventions ( BSIs ) for children with NNDDs and comorbid sleep disturbances . | Although melatonin and cognitive-behavioural therapy have shown efficacy in treating sleep disorders in children with autism spectrum disorders , little is known about their relative or combined efficacy . One hundred and sixty children with autism spectrum disorders , aged 4 - 10 years , suffering from sleep onset insomnia and impaired sleep maintenance , were assigned r and omly to either ( 1 ) combination of controlled-release melatonin and cognitive-behavioural therapy ; ( 2 ) controlled-release melatonin ; ( 3 ) four sessions of cognitive-behavioural therapy ; or ( 4 ) placebo drug treatment condition for 12 weeks in a 1 : 1 : 1 : 1 ratio . Children were studied at baseline and after 12 weeks of treatment . Treatment response was assessed with 1-week actigraphic monitoring , sleep diary and sleep question naire . Main outcome measures , derived actigraphically , were sleep latency , total sleep time , wake after sleep onset and number of awakenings . The active treatment groups all result ed in improvements across all outcome measures , with moderate-to-large effect sizes from baseline to a 12-week assessment . Melatonin treatment was mainly effective in reducing insomnia symptoms , while cognitive-behavioural therapy had a light positive impact mainly on sleep latency , suggesting that some behavioural aspects might play a role in determining initial insomnia . The combination treatment group showed a trend to outperform other active treatment groups , with fewer dropouts and a greater proportion of treatment responders achieving clinical ly significant changes ( 63.38 % normative sleep efficiency criterion of > 85 % and 84.62 % , sleep onset latency < 30 min ) . This study demonstrates that adding behavioural intervention to melatonin treatment seems to result in a better treatment response , at least in the short term BACKGROUND Children with high-functioning autism spectrum disorders ( ASD ) are at high risk for developing significant anxiety . Anxiety can adversely impact functioning across school , home and community environments . Cognitive behavioral therapies ( CBT ) are frequently used with success for children with anxiety symptoms . Modified CBT interventions for anxiety in children with ASD have also yielded promising results . METHODS Fifty children with high-functioning ASD and anxiety were r and omizedto group CBT or treatment-as-usual ( TAU ) for 12 weeks . Independent clinical evaluators , blind to condition , completed structured interviews ( Anxiety Disorders Interview Schedule – Parent Version;ADIS-P ) pre- and post-intervention condition . RESULTS Forty-seven children completed either the CBT or TAU condition . Results indicated markedly better outcomes for the CBT group . Significant differences by group were noted in Clinician Severity Ratings , diagnostic status , and clinician ratings of global improvement . In the intent-to-treat sample , 10 of 20 children ( 50 % ) in the CBT group had a clinical ly meaningful positive treatment response , compared to 2 of 23 children ( 8.7 % ) in the TAU group . CONCLUSIONS Initial results from this r and omized , design ed treatment study suggest that agroup CBT intervention specifically developed for children with ASD may be effective in decreasing anxiety . Limitations of this study include small sample size , lack of an attention control group , and use of outcome measures normed with typically developing OBJECTIVE Better Nights/Better Days , a distance intervention for insomnia in school-aged children ( with and without attention-deficit/hyperactivity disorder [ ADHD ] ) , was evaluated to determine its effectiveness on children 's sleep and psychosocial functioning . METHODS A single center , parallel group design r and omized controlled trial ( stratified on ADHD diagnosis ) was conducted . Parents were r and omized to intervention ( n = 31 ) or waitlist control ( n = 30 ) , and completed question naires administered over the phone at baseline , postintervention ( 2 months ) , and follow-up ( 6 months ) . Actigraphy was also collected . The intervention consisted of a five-session manual and weekly telephone coach support . RESULTS The intervention group demonstrated a significant reduction in sleep problems and improved psychosocial functioning at postintervention and follow-up . Actigraphy results indicated improved sleep onset , but not sleep duration . Children with and without ADHD responded in a similar manner to this intervention . Parents provided high satisfaction ratings . CONCLUSIONS This intervention holds promise as an accessible , sustainable , and effective program to address insomnia in school-aged children Objective To examine whether behavioural strategies design ed to improve children ’s sleep problems could also improve the symptoms , behaviour , daily functioning , and working memory of children with attention deficit hyperactivity disorder ( ADHD ) and the mental health of their parents . Design R and omised controlled trial . Setting 21 general paediatric practice s in Victoria , Australia . Participants 244 children aged 5 - 12 years with ADHD attending the practice s between 2010 and 2012 . Intervention Sleep hygiene practice s and st and ardised behavioural strategies delivered by trained psychologists or trainee paediatricians during two fortnightly consultations and a follow-up telephone call . Children in the control group received usual clinical care . Main outcome measures At three and six months after r and omisation : severity of ADHD symptoms ( parent and teacher ADHD rating scale IV— primary outcome ) , sleep problems ( parent reported severity , children ’s sleep habits question naire , actigraphy ) , behaviour ( strengths and difficulties question naire ) , quality of life ( pediatric quality of life inventory 4.0 ) , daily functioning ( daily parent rating of evening and morning behavior ) , working memory ( working memory test battery for children , six months only ) , and parent mental health ( depression anxiety stress scales ) . Results Intervention compared with control families reported a greater decrease in ADHD symptoms at three and six months ( adjusted mean difference for change in symptom severity −2.9 , 95 % confidence interval −5.5 to −0.3 , P=0.03 , effect size −0.3 , and −3.7 , −6.1 to −1.2 , P=0.004 , effect size −0.4 , respectively ) . Compared with control children , intervention children had fewer moderate-severe sleep problems at three months ( 56 % v 30 % ; adjusted odds ratio 0.30 , 95 % confidence interval 0.16 to 0.59 ; P<0.001 ) and six months ( 46 % v 34 % ; 0.58 , 0.32 to 1.0 ; P=0.07 ) . At three months this equated to a reduction in absolute risk of 25.7 % ( 95 % confidence interval 14.1 % to 37.3 % ) and an estimated number needed to treat of 3.9 . At six months the number needed to treat was 7.8 . Approximately a half to one third of the beneficial effect of the intervention on ADHD symptoms was mediated through improved sleep , at three and six months , respectively . Intervention families reported greater improvements in all other child and family outcomes except parental mental health . Teachers reported improved behaviour of the children at three and six months . Working memory ( backwards digit recall ) was higher in the intervention children compared with control children at six months . Daily sleep duration measured by actigraphy tended to be higher in the intervention children at three months ( mean difference 10.9 minutes , 95 % confidence interval −19.0 to 40.8 minutes , effect size 0.2 ) and six months ( 9.9 minutes , −16.3 to 36.1 minutes , effect size 0.3 ) ; however , this measure was only completed by a subset of children ( n=54 at three months and n=37 at six months ) . Conclusions A brief behavioural sleep intervention modestly improves the severity of ADHD symptoms in a community sample of children with ADHD , most of whom were taking stimulant medications . The intervention also improved the children ’s sleep , behaviour , quality of life , and functioning , with most benefits sustained to six months post-intervention . The intervention may be suitable for use in primary and secondary care . Trial registration Current Controlled Trials IS RCT N68819261 OBJECTIVE Sleep difficulties are common reasons why parents seek medical intervention in children with autism spectrum disorders ( ASDs ) . We determined whether a pamphlet alone could be used by parents to help their child ’s insomnia . METHODS Thirty-six children with ASD , ages 2 to 10 years , were enrolled . All had prolonged sleep latency confirmed by actigraphy showing a mean sleep latency of 30 minutes or more . Parents were r and omly assigned to receive the sleep education pamphlet or no intervention . Children wore an actigraphy device to record baseline sleep parameters , with the primary outcome variable being change in sleep latency . Actigraphy data were collected a second time 2 weeks after the parent received the r and omization assignment and analyzed by using Student ’s t test . Parents were also asked a series of questions to gather information about the pamphlet and its usefulness . RESULTS Although participants r and omized to the 2 arms did not differ statistically in age , gender , socioeconomic status , total Children ’s Sleep Habits Question naire score , or actigraphy parameters , some differences may be large enough to affect results . Mean change in sleep-onset latency did not differ between the r and omized groups ( pamphlet versus no pamphlet ) . Parents commented that the pamphlet contained good information , but indicated that it would have been more useful to be given specific examples of how to take the information and put it into practice . CONCLUSIONS A sleep education pamphlet did not appear to improve sleep latency in children with ASDs Background : Settling and night waking problems are particularly prevalent , persistent , and generally considered difficult to treat in children with a learning disability , although intervention trials are few . Scarce re sources , however , limit access to proven behavioural treatments . Aims : To investigate the efficacy of a media based brief behavioural treatment of sleep problems in such children by comparing ( 1 ) face-to-face delivered treatment versus control and ( 2 ) booklet delivered treatment versus controls . Methods : The parents of 66 severely learning disabled children aged 2–8 years with settling and /or night waking problems took part in a r and omised controlled trial with a wait-list control group . Behavioural treatments were presented either conventionally face-to-face or by means of a 14 page easy to read illustrated booklet . A composite sleep disturbance score was derived from sleep diaries kept by parents . Results : Both forms of treatment were almost equally effective compared with controls . Two thirds of children who were taking over 30 minutes to settle five or more times per week and waking at night for over 30 minutes four or more times per week improved on average to having such settling or night waking problems for only a few minutes or only once or twice per week ( H = 34.174 , df = 2 , p<0.001 ) . These improvements were maintained after six months . Conclusions : Booklet delivered behavioural treatments for sleep problems were as effective as face-to-face treatment for most children in this population Abstract Objectives . We tested the hypothesis that sleep training would improve emotional , social and behavioural functioning in children with attention-deficit/hyperactivity disorder ( ADHD ) compared to children with ADHD without such intervention and to healthy controls . Methods . Forty children with ADHD were r and omly assigned to intervention and control conditions . Parents of 20 children with ADHD were instructed and thoroughly supervised in improving their children 's sleep schedules and sleep behaviour . Parents of the other 20 children with ADHD and parents of 20 healthy children received general information about sleep hygiene . At baseline and 12 weeks later , parents and children completed question naires related to children 's sleep and psychological functioning . Results . Relative to the control groups , children in the intervention group improved sleep quantitatively and qualitatively ( F values < 3.33 , P values < 0.05 ) . The intervention group children reported improvements in mood , emotions , and relationships ( F values < 2.99 , P values < 0.05 ) . Parents reported that their children improved in physical and psychological wellbeing , mood , emotions , relationships , and social acceptance ( F values < 3.02 , P values < 0.05 ) . Conclusions . Training and monitoring parents of children with ADHD in regulating and supervising children 's sleep schedules leads to positive changes in the emotions , behaviour and social lives of these children OBJECTIVE To examine associations between sleep problems during development and subsequent emotional and behavioral difficulties . DESIGN Prospect i ve longitudinal study . SETTING The Dutch province of Zuid-Holl and . PARTICIPANTS At time 1 of data collection , a representative sample of 2076 children aged 4 to 16 years participated in the study . OUTCOME MEASURES Parents rated their children 's ( 4 - 19 years old ) sleep at 5 assessment s by completing the Child Behavior Checklist . Participants reported on their own emotional and behavioral symptoms at a later assessment ( when aged 18 - 32 years ) by completing the Young Adult Self-Report . RESULTS After adjusting for sex , age , socioeconomic status , and parent-rated scores through development for the difficulty being predicted , having any parental reports of sleeping less than others was a risk indicator of high scores on the Anxious/Depressed scale ( odds ratio , 1.43 ; 95 % confidence interval , 1.07 - 1.90 ; P = .01 ) and the Aggressive Behavior scale ( odds ratio , 1.51 ; 95 % confidence interval , 1.13 - 2.02 ; P = .005 ) . There was some ( albeit less robust ) support for links between other reported sleep difficulties and later problems . Parental reports of sleeping more than others and nightmares were not associated with later difficulties . CONCLUSIONS Physicians should inquire about sleep problems during child development and should be aware that some , but perhaps not others , may constitute risk indicators of later difficulties Objective : Sleep problems are common in children with autism spectrum disorders ( ASD ) and ADHD and impact adversely on child and parent well-being . The study evaluated the efficacy of a brief behavioral sleep intervention in children with comorbid ADHD – ASD . Method : A sub sample of children with ADHD – ASD ( n = 61 ; 5 - 13 years ; 89 % male ) participating in the Sleeping Sound With ADHD study were included in the current investigation . The sub sample comprised of 28 children r and omized to the sleep intervention group , while 33 were r and omized to usual clinical care . The intervention consisted of two clinical consultations and a follow-up phone call covering sleep hygiene and st and ardized behavioral strategies . Results : Children with ADHD – ASD who received the intervention had large improvements in sleep problems and moderate improvements in child behavioral functioning 3 and 6 months post-r and omization . Conclusion : These findings suggest that a brief behavioral sleep intervention can improve sleep problems in children with ADHD – ASD OBJECTIVES The study aim ed to assess the mental state of mothers and fathers following successful behavioural intervention for sleep problems in such children . DESIGN A r and omized controlled trial of behavioural interventions for sleep problems . METHODS Parents of 15 children with severe intellectual disabilities , severe sleep problems , and challenging daytime behaviour received treatment for the child 's sleep problem and were compared with 15 controls who received no treatment . Parental stress , sleepiness , locus of control , perceived control , and satisfaction with aspects of sleep were assessed . RESULTS Successful treatment benefited the mothers , reducing stress , increasing perceived control and making them more satisfied with their sleep , their child 's sleep , and their ability to cope with their child 's sleep . Positive effects in the fathers were limited to increased satisfaction with their own sleep and their child 's sleep ; fathers tended to feel less control following treatment . Maternal sleepiness and perceived control , and aspects of parental satisfaction showed improvements in both the treatment and control groups . CONCLUSION The effects of childhood sleep problems , and their resolution using behavioural interventions , may be different in mothers and fathers . This highlights the need to assess all family members in order to gain a greater underst and ing of how best to help families as a whole . The improvements in both control and treatment groups indicate that there may be non-specific effects of taking part in the study that played a therapeutic role Children with sleep problems present serious management problems to their parents . Such children are also more likely to have additional problems , behavioural disturbance being particularly common . This r and omized controlled trial of behavioural interventions for the children 's sleep problems was conducted to explore the efficacy and mechanisms of treatment in children with the most extreme forms of problems : severe learning disabilities , severe sleep problems and severe daytime challenging behaviour . Fifteen index families received behavioural advice for the child 's sleep problem and compared with 15 matched controls who received no such advice . Repeat assessment s of the children 's and mothers ' sleep were made by parental report as well as actometry . Objective changes in the children 's sleep quality and quantity were not seen after treatment . However , mothers in the treatment group reported improvements in the children 's sleep problems and had an increased sleeping time themselves following treatment . The results indicate that sleep problems can be successfully treated in this group of children , although the mechanisms of treatment may not be as direct as supposed . This has implication s for underst and ing of sleep problems in children with learning disabilities and also for clinical practice , when considering ways of offering help to these highly ' challenged ' families The study aim ed to investigate a group of children with severe learning disabilities , challenging daytime behaviour , and severe sleep problems to see if successful behavioural treatment of the children 's sleep problems result ed in reduced daytime challenging behaviour as reported by mothers and teachers . A r and omised controlled trial of behavioural interventions for the children 's sleep problems was conducted ( N = 30 ) . The intervention group received an individually tailored behavioural programme and were supported by telephone calls from the therapist . Baseline assessment s of the children 's behaviour were made using the Aberrant Behavior Checklist and were repeated 1 month and 3 months after the start of intervention . There were no behavioural changes that were specific to children in the treatment group . However , improvements in some behaviours were seen in both the intervention and the control group at the 1-month and 3-month assessment s and there was agreement between mothers ' and teachers ' reports for many of these changes . The results suggest that nonspecific effects of participating in the study ( including an increased sleep duration , which was seen in both groups ) , rather than resolution of sleep problem per se , may have a beneficial effect on child behaviour and these factors need to be identified for therapeutic use OBJECTIVES A large percentage of children with autism spectrum disorders ( ASD ) have bedtime and sleep disturbances . However , the treatment of these disturbances has been understudied . The purpose of our study was to develop a manualized behavioral parent training ( BPT ) program for parents of young children with ASD and sleep disturbances and to test the feasibility , fidelity , and initial efficacy of the treatment in a small r and omized controlled trial ( RCT ) . PARTICIPANTS AND METHODS Parents of a sample of 40 young children diagnosed with ASD with an average age of 3.5years were enrolled in our study . Participants were r and omized to either the BPT program group or a comparison group who were given nonsleep-related parent education . Each participant was individually administered a 5-session program delivered over the 8-week study . Outcome measures of feasibility , fidelity , and efficacy were collected at weeks 4 and 8 after the baseline time point . Children 's sleep was assessed by parent report and objective ly by actigraphy . RESULTS Of the 20 participants in each group , data were available for 15 participants r and omized to BPT and 18 participants r and omized to the comparison condition . Results supported the feasibility of the manualized parent training program and the comparison program . Treatment fidelity was high for both groups . The BPT program group significantly improved more than the comparison group based on the primary sleep outcome of parent report . There were no objective changes in sleep detected by actigraphy . CONCLUSIONS Our study is one of few RCTs of a BPT program to specifically target sleep disturbances in a well-characterized sample of young children with ASD and to demonstrate the feasibility of the approach . Initial efficacy favored the BPT program over the comparison group and suggested that this manualized parent training approach is worthy of further examination of the efficacy within a larger RCT |
1,209 | 18,555,682 | Imatinib greatly improved HRQOL compared to interferon based treatments in CML patients and fludarabine plus cyclophosphamide does not seem to have a deleterious impact on patient 's HRQOL when compared to fludarabine alone or chlorambucil in CLL patients .
This study revealed the paucity of HRQOL research in leukaemia patients .
Nonetheless , HRQOL assessment is feasible in RCTs and has the great potential of providing valuable outcomes to further support clinical decision making | Health-related quality of life ( HRQOL ) is increasingly reported as an important outcome in cancer clinical trials .
However , very little evidence exists on the impact of such evaluation in r and omised controlled trials ( RCTs ) of leukaemia patients . | Treatment of chronic myeloid leukaemia ( CML ) with IFN-alpha ( IFN ) is known to confer significant survival benefit , but the drug 's impact on quality of life ( QoL ) in CML is unclear . We describe a cross-sectional comparison of QoL in patients r and omised to long-term treatment with IFN versus no IFN within the UK MRC CML 3 trial , assessing the long-term consequences and psychosocial side effects of IFN therapy . Patients completed the EORTC QoL QLQ-C30 , an in-house leukaemia/IFN question naire , a brief assessment of sexual functioning and demographic details . In total , 163 eligible patients completed question naires ( 85 % response ) . Patients receiving IFN reported significantly worse QoL for emotional , cognitive and social functioning , pain and dyspnoea ( P<0.01 ) , and marginally worse fatigue , nausea and vomiting ( P<0.05 ) . As expected from other IFN use , those on IFN experienced more flu-like and febrile symptoms and skin problems than those not on IFN . In all , 35 % of patients stopped IFN before question naire completion . This made no material difference to the results , except that those continuing on IFN had slightly better self-assessed Global health/QoL than those who had stopped ( P<0.03 ) . IFN treatment adversely affected sexual health after allowing for age and gender . In conclusion , IFN treatment has a significant adverse impact on QoL. Patient awareness of the survival benefits and these QoL effects should enable better-informed decision-making . The impact on QoL of IFN dose , and of imatinib therapy versus IFN in early CP CML , are being investigated . QoL will need evaluating in future studies of combination treatment ( IFN+imatinib ) PURPOSE We conducted a phase III trial to determine whether first-line treatment with raltitrexed , a thymidine synthase inhibitor , and cisplatin results in superior outcome compared with cisplatin alone in patients with malignant pleural mesothelioma ( MPM ) . PATIENTS AND METHODS Eligible patients with histologically proven advanced MPM , not pretreated with chemotherapy , WHO performance status ( PS ) 0 to 2 , and adequate hematological , renal , and hepatic function were r and omly assigned to receive cisplatin 80 mg/m2 IV on day 1 , alone ( arm A ) or combined with raltitrexed 3 mg/m2 ( arm B ) . In patients with measurable disease , response was monitored using the Response Evaluation Criteria in Solid Tumors criteria . Health related quality of life ( HRQOL ) was measured using the European Organisation for Research and Treatment of Cancer QLQ-C30 and Lung Module ( QLQ-LC13 ) . RESULTS Two hundred fifty patients were r and omized : 80 % male ; median age , 58 years ; and WHO PS , 0 , 1 , 2 in 25 , 62 , and 13 % of cases , respectively . There were no toxic deaths . The main grade 3 or 4 toxicities observed were neutropenia and emesis , reported twice as often in the combination arm . Among 213 patients with measurable disease , response rate was 13.6 % ( arm A ) versus 23.6 % ( arm B ; P = .056 ) . No difference in HRQOL was observed on any of the scales . Median overall and 1-year survival in arms A and B were 8.8 ( 95 % CI , 7.8 to 10.8 ) v 11.4 months ( 95 % CI , 10.1 to 15 ) , respectively , and 40 % v 46 % , respectively ( P = .048 ) . CONCLUSION A combination of raltitrexed and cisplatin improves overall survival compared with cisplatin alone . This study confirms that a combination of cisplatin and an antifolate is superior to cisplatin alone in patients with MPM , without harmful effect on HRQOL 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 The increasing success of intensive consolidation chemotherapy ( CCT ) as an alternative to bone marrow transplant ( BMT ) in acute myeloid leukaemia ( AML ) necessitates comparison of the impact on quality of life ( QoL ) of these two treatment modalities . Most QoL studies following BMT involve small patient numbers and provide ambivalent results . The present study examines QoL in a large number of patients 1 year from the end of treatment within the United Kingdom Medical Research Council ( UK MRC ) AML10 trial of BMT versus CCT . Allogeneic-BMT ( Allo-BMT ) was observed to have an adverse impact on most QoL dimensions compared with Autologous-BMT ( A-BMT ) and CCT . More patients receiving BMT had mouth dryness problems and worse sexual and social relationships , professional and leisure activities than CCT patients . QoL in A-BMT patients was less impacted than Allo-BMT . Intention-to-treat analysis showed similar results . These results indicate that a reconsideration of treatment strategies is warranted , and that further , good prospect i ve studies are needed to evaluate more clearly the effects of these treatments in long-term survivors The objective of this study was to obtain age- and sex-specific reference values for the European Organization for Research and Treatment of Cancer ( EORTC ) Quality of Life Question naire QLQ-C30 . A r and omly selected sample of the German adult population ( 3015 subjects ) was used , 2081 subjects agreed to take part in the investigation . Most of the scales and symptom items of the question naire proved to be dependent on age and sex . Men reported fewer symptoms than women . Age differences were even more pronounced . Younger people reported better functioning and fewer symptoms . Compared with the results of a similar Norwegian study ( Hjermstad MJ , Fayers PM , Bjordal K , Kaasa S. Health related quality of life in the general Norwegian population assessed by the European Organization for research and treatment of cancer core quality -of-life question naire : The QLQ-C30(+3 ) . J Clin Oncol 1998 , 16 , 1188 - 1196 ) the prevalence of some symptoms was markedly less . Norm values for age and sex groups are given and regression analyses are performed which help to calculate expected mean scores . The results show that age and sex differences must be taken into consideration when different groups of cancer patients are compared . The norm values help to interpret quality of life data for clinicians PURPOSE To date , only a few studies have evaluated the health-related quality of life ( HRQOL ) of patients with chronic lymphocytic leukemia ( CLL ) receiving chemotherapy . Therefore , the German CLL Study Group assessed HRQOL in younger patients with advanced CLL receiving first-line chemotherapy with fludarabine or fludarabine plus cyclophosphamide ( FC ) . PATIENTS AND METHODS Three hundred seventy-five patients younger than 66 years with advanced CLL were r and omly assigned to receive either fludarabine alone ( fludarabine 25 mg/m2/d for 5 days intravenously [ IV ] , repeated every 28 days ) or FC ( fludarabine 30 mg/m2/d for 3 days IV plus cyclophosphamide 250 mg/m2/d for 3 days , repeated every 28 days ) . Six courses of treatment were planned to be administered . The European Organisation for Research and Treatment of Cancer Quality of Life Question naire C30 was sent to all patients at baseline and after 6 , 12 , and 24 months . RESULTS Eighty-nine percent of 362 included patients completed at least one question naire ( 163 fludarabine- and 158 FC-treated patients ) . Comparing the baseline levels of 249 CLL patients with the general German population , significant differences in nearly all HRQOL scales were assessed between the two groups . A multivariate analysis showed no significant differences in all HRQOL scales between both arms . In both treatment arms , symptoms such as fatigue , insomnia , and appetite loss improved to lower levels after the end chemotherapy . Except for lower physical status , no significant difference in HRQOL between male and female patients was evaluated . CONCLUSION Fludarabine-based treatment seems to improve HRQOL little to moderately in younger patients with advanced CLL . No significant difference between fludarabine- and FC-treated patients was observed A cross-sectional study of quality of life ( QOL ) was performed in 98 patients in continued first complete remission ( CR ) for 1–7.4 years , after inclusion in the AML 8A trial which prospect ively compared allogeneic bone marrow transplantation ( AlloBMT ) , autologous BMT ( ABMT ) and intensive consolidation chemotherapy . Several significant differences between the three treatment groups were observed , on the basis of patient self-reports , with regard to somatic symptoms ( mouth sores , cough , hair loss , headache ) , repeated acute medical problems , physical functioning , role functioning , leisure activities and , above all , sexual functioning . There were also significant differences for overall physical condition , and overall quality of life . For all these parameters , the ranking was uniformly AlloBMT lower than ABMT lower than chemotherapy . These differences remain significant after adjustment for time interval between CR and QOL evaluation , sex or age . These results , confirming a higher risk of permanent impairment of QOL after BMT , may have an impact on medical decisions and warrant further studies BACKGROUND Previous work highlighted a number of method ological constraints when reporting health-related quality of life ( HRQOL ) outcomes from r and omized controlled trials ( RCTs ) . Given this , the objective of this study was to investigate whether the quality of such HRQOL reports has improved over time . MATERIAL S AND METHODS On the basis of a predefined set of criteria , 159 RCTs with a HRQOL end point , published between 1990 and 2004 were identified and analyzed . Each study was evaluated by a number of issues ( e.g. sample size and industry sponsorship ) and by the " minimum st and ard checklist for evaluating HRQOL outcomes in cancer clinical trials " . RESULTS The quality of HRQOL reports , as measured by the overall checklist score , was independently related to more recently published studies ( P < 0.0001 ) . This relationship was independent of industry funded , HRQOL end point ( primary versus secondary ) , cancer disease site , size of the study and HRQOL difference between treatment arms . While only 39.3 % of studies published between 1990 and 2000 ( 89/159 RCTs ) were identified as being probably robust , thus likely to support clinical decision making , this percentage was 64.3 % for studies published after 2000 ( 70/159 RCTs ) . CONCLUSION Since we found a significant learning curve in HRQOL trial reporting since 1990 , it can be expected that HRQOL data will increasingly impact on clinical decision making and treatment policies in the near future Federal regulations provide 2 pathways for approval of new agents for the treatment of acute leukemia , regular and accelerated approval . Regular approval requires evidence of clinical benefit , which is generally defined as either prolongation of life or improved quality of life , or an effect on an end point established as a surrogate for clinical benefit . Accelerated approval can be obtained based on demonstration of an effect on a surrogate measure " reasonably likely " to predict clinical benefit , but requires demonstration of clinical benefit after approval as well . The acute leukemias are a heterogeneous and relatively uncommon group of diseases . The design and execution of prospect i ve r and omized clinical trials demonstrating prolongation of life or improved quality of life for patients with these disorders can be difficult and costly and require lengthy follow-up . Thus , the development of novel trial design and inclusion of vali date d surrogate markers for clinical benefit are needed . To explore some of the issues pertinent to the choice of end points for drug approval in acute leukemia , the Food and Drug Administration invited the American Society of Hematology to participate in the organization and conduct of a joint workshop . In this report , we present the results of that effort BACKGROUND Imatinib , a selective inhibitor of the BCR-ABL tyrosine kinase , produces high response rates in patients with chronic-phase chronic myeloid leukemia ( CML ) who have had no response to interferon alfa . We compared the efficacy of imatinib with that of interferon alfa combined with low-dose cytarabine in newly diagnosed chronic-phase CML . METHODS We r and omly assigned 1106 patients to receive imatinib ( 553 patients ) or interferon alfa plus low-dose cytarabine ( 553 patients ) . Crossover to the alternative group was allowed if stringent criteria defining treatment failure or intolerance were met . Patients were evaluated for hematologic and cytogenetic responses , toxic effects , and rates of progression . RESULTS After a median follow-up of 19 months , the estimated rate of a major cytogenetic response ( 0 to 35 percent of cells in metaphase positive for the Philadelphia chromosome ) at 18 months was 87.1 percent ( 95 percent confidence interval , 84.1 to 90.0 ) in the imatinib group and 34.7 percent ( 95 percent confidence interval , 29.3 to 40.0 ) in the group given interferon alfa plus cytarabine ( P<0.001 ) . The estimated rates of complete cytogenetic response were 76.2 percent ( 95 percent confidence interval , 72.5 to 79.9 ) and 14.5 percent ( 95 percent confidence interval , 10.5 to 18.5 ) , respectively ( P<0.001 ) . At 18 months , the estimated rate of freedom from progression to accelerated-phase or blast-crisis CML was 96.7 percent in the imatinib group and 91.5 percent in the combination-therapy group ( P<0.001 ) . Imatinib was better tolerated than combination therapy . CONCLUSIONS In terms of hematologic and cytogenetic responses , tolerability , and the likelihood of progression to accelerated-phase or blast-crisis CML , imatinib was superior to interferon alfa plus low-dose cytarabine as first-line therapy in newly diagnosed chronic-phase CML This is an up date of a r and omized study on antithymocyte globulin ( ATG ; Thymoglobulin ) before transplantation in patients undergoing unmanipulated marrow transplantation from unrelated donors . The median follow-up for surviving patients is 5.7 years . At last follow-up , chronic graft-versus-host disease ( GVHD ) was scored in 60 % of non-ATG and in 37 % of ATG patients ( P=.05 ) , and extensive chronic GVHD was present in 41 % and 15 % , respectively ( P=.01 ) . Chronic lung dysfunction was diagnosed in 51 % versus 19 % of patients ( P=.005 ) . Forced vital capacity decreased significantly with time in non-ATG patients ( P=.005 ) , but not in patients who received ATG ( P=.30 ) . The proportion of patients with Karnofsky scores of > or=90 % at 4 years was 57 % versus 89 % in non-ATG versus ATG patients ( P=.03 ) . The actuarial 6-year survival for all patients r and omized was 31 % versus 44 % ( non-ATG versus ATG ; P=.80 ) . The cumulative incidence of transplant-related mortality was 51 % versus 41 % ( P=.70 ) and of relapse was 32 % versus 40 % ( P=.90 ) . For patients who survived 1 year , transplant-related mortality was 25 % versus 3 % ( P=.03 ) , and actuarial survival was 58 % versus 85 % ( P=.09 ) . In conclusion , the addition of ATG to cyclosporine/methotrexate provides significant protection against extensive chronic GVHD and chronic lung dysfunction , reduces late transplant mortality , and improves quality of life in patients undergoing unrelated donor transplantation We conducted a prospect i ve , r and omized , multicentre clinical trial comparing the effects and costs of GM-CSF as an adjunct to intensive chemotherapy in elderly patients with acute myeloid leukaemia ( AML ) . The patients were r and omized to either daunomycin-cytosine arabinoside ( control arm : n = 161 ) or daunomycin-cytosine arabinoside with GM-CSF ( GM-CSF arm : n = 157 ) . The primary end-point was the effect of GM-CSF on the percentage of complete remissions ( CR ) . Survival duration , disease-free survival , quality of life and costs were evaluated separately . CR after remission induction treatment was achieved in 55 % of the patients in the control group and in 56 % of the patients in the GM-CSF group ( P = NS ) . The duration of survival and disease-free survival at 2 years after r and omization were estimated at 22 % and 19 % for the control group and 22 % and 14 % for the GM-CSF group ( P = NS ) . Considering the short-term quality of life , the administration of GM-CSF result ed in more problems with regard to depressed mood , diarrhoea and rash/eczema . With regard to the long-term quality of life there were no significant differences between the two groups . The average costs of the primary treatment were higher in GM-CSF-treated patients than in the control group , i.e. US$ 40782 and US$ 34465 , respectively ( P < 0.01 ) . The costs during the follow-up period did not differ between the two groups . The results of this r and omized clinical trial indicate that daunomycin-cytosine arabinoside plus GM-CSF is not a cost-effective treatment strategy when compared with daunomycin-cytosine arabinoside alone Combination chemotherapy with fludarabine plus cyclophosphamide ( FC ) was compared with the st and ard regimen of fludarabine monotherapy in first-line treatment of younger patients with chronic lymphocytic leukemia ( CLL ) . Between 1999 and 2003 , a total of 375 patients younger than 66 years who predominantly had advanced CLL were r and omly assigned to receive either fludarabine ( 25 mg/m(2 ) for 5 days intravenously , repeated every 28 days ) or FC combination therapy ( fludarabine 30 mg/m(2 ) plus cyclophosphamide 250 mg/m(2 ) for 3 days intravenously , repeated every 28 days ) . Both regimens were administered to a maximum of 6 courses . FC combination chemotherapy result ed in significantly higher complete remission rate ( 24 % ) and overall response rate ( 94 % ) compared with fludarabine alone ( 7 % and 83 % ; P < .001 and P = .001 ) . FC treatment also result ed in longer median progression-free survival ( 48 vs 20 months ; P = .001 ) and longer treatment-free survival ( 37 vs 25 months ; P < .001 ) . Thus far , no difference in median overall survival has been observed . FC caused significantly more thrombocytopenia and leukocytopenia but did not increase the number of severe infections . In summary , first-line treatment with FC increases the response rates and the treatment-free interval in younger patients with advanced CLL BACKGROUND A r and omised controlled trial of radiotherapy alone versus radiotherapy with concomitant and adjuvant temozolomide for patients with glioblastoma showed that survival was higher for patients assigned combination treatment compared with those assigned st and ard radiotherapy alone . This paper reports the health-related quality of life ( HRQOL ) of the patients in this trial . METHODS 573 patients with newly diagnosed glioblastoma were r and omly allocated either radiotherapy alone or radiotherapy and temozolomide . The primary endpoint was survival , and HRQOL was a secondary endpoint . We assessed HRQOL at baseline and at every 3 months during treatment until progression using the European Organisation for Research and Treatment of Cancer ( EORTC ) quality of life question naire core-30 ( QLQ-C30 ) and the EORTC brain cancer module ( EORTC BN-20 ) . We calculated changes from baseline score for seven predefined HRQOL measures ( fatigue , overall health , social function , emotional function , future uncertainty , insomnia , and communication deficit ) and differences between groups for these measures at every time point . The significance of , and proportions of patients with , improved HRQOL scores -- defined as a change of 10 points or more -- were recorded . This trial is registered on the US National Cancer Institute website http://www.cancer.gov/ search /New Clinical Trials , NCT00006353 . FINDINGS Baseline question naires were available for 490 ( 86 % ) patients . Baseline HRQOL scores did not differ between groups . At first follow-up , groups differed only in social functioning , favouring the radiotherapy-only group ( mean score 79.0 [ SD 3.2 ] for patients assigned radiotherapy vs 67.4 [ 2.7 ] for those assigned radiotherapy and temozolomide ; difference between groups 11.6 points [ 95 % CI 3.5 - 19.7 ] , p=0.0052 ) . Over subsequent assessment s , HRQOL was much the same between treatment groups . INTERPRETATION Addition of temozolomide during and after radiotherapy for patients with newly diagnosed glioblastoma significantly improved survival without a negative effect on HRQOL Summary . Patients under 55 years in the United Kingdom Medical Research Council Acute Myeloid Leukaemia 10 trial who entered complete remission were tissue typed ( n = 1063 ) . Four hundred and nineteen had a matched sibling donor and 644 had no match . When compared on a donor versus no donor basis the relapse risk was reduced in the donor arm ( 36%vs 52 % ; P = 0·001 ) and the disease‐free survival ( DFS ) improved ( 50%vs 42 % ; P = 0·01 ) , but overall survival ( OS ) was not different ( 55%vs 50 % ; P = 0·1 ) . Sixty‐one per cent of patients with a donor underwent transplantation . When patients were subdivided into risk groups based on cytogenetics alone or with the addition of blast response to course 1 , a reduction in relapse risk was seen in all risk groups and in three age cohorts ( 0–14 , 15–34 and 35 + years ) . Significant benefit in DFS was only seen in the intermediate‐risk cytogenetic group ( 50%vs 39 % ; P = 0·004 ) . The OS benefit was only seen in intermediate‐risk patients ( 55%vs 44 % ; P = 0·02 ) . The reduction in relapse risk in good‐risk patients was attributable to patients with t(15;17 ) and not to patients with t(8;21 ) or inv(16 ) . Allogeneic transplantation given after intensive chemotherapy was able to reduce relapse in all risk and age groups . However , due to the competing effects of procedural mortality and an inferior response to chemotherapy if relapse does occur , there was a survival advantage only in patients of intermediate risk . This trial found no survival advantage in children , patients over 35 years or good‐risk disease From a main study describing quality of life in patients with acute myeloid leukaemia ( AML ) over time , 22 patients who had received induction treatment with POCAL ( prednisone , vincristine , doxorubicin , Ara-C , thioguanine ) , MEA ( mitoxantrone , etoposide , Ara-C ) or TAD ( daunorubicin , Ara-C , thioguanine ) chemotherapy regimens were selected . Their quality of life was assessed with Karnofsky performance scale ( KPS ) and Vitagram as well as with life ingredient profile ( LIP ) , a new instrument for assessing quality of life during chemotherapy treatment . The patients ' quality of life was found to be affected for short periods during induction treatment . The POCAL regimen seemed to lead to the least deterioration in quality of life , whereas the MEA treatment had more pronounced effects in this respect . In patients treated according to the TAD regimen gastrointestinal side-effects were mild compared to those of the other regimens . However , to show significant differences between treatment regimens larger multicentre studies are needed . The LIP instrument appeared to display a superior capacity for evaluating the distress of patients compared with the other instruments The optimal dose of interferon-alfa ( IFN ) for chronic myeloid leukemia ( CML ) is unknown . Retrospective analyses suggest that low doses are as effective as high doses , with less toxicity and fewer patients ab and oning the drug . The Dutch Hemato-Oncology Association ( HOVON ) and British Medical Research Council ( MRC ) cooperative groups jointly performed r and omized trials in newly diagnosed CML patients , comparing high-dose IFN ( 5 MIU/m(2 ) daily ) with low-dose ( 3 MIU , 5 times a week ) . Both arms allowed additional hydroxyurea to keep the white blood cell count lower than 5 x 10(9)/L. Quality of life data were collected in a subset of patients . Between 1993 and 2001 , 407 patients were r and omized . At a median follow-up of 53 months , there were no significant differences in overall survival ( odds ratio = 1.09 , 95 % confidence interval , 0.81 - 1.46 ) , progression-free survival , and complete hematologic or major cytogenetic responses . Fewer patients in the low-dose group ab and oned IFN for reasons other than transplant or progressive disease ( P = .002 , 58 % vs 72 % at 5 years ) . Quality of life data showed comparable results in both arms for most factors . There is no evidence of benefit for high-dose IFN compared with low-dose for the treatment of CML . Therefore , when IFN is combined with other drugs , low-dose IFN is advised , to minimize toxicity and costs Interferon-alpha may be better than cytotoxic drugs in the long-term management of patients with chronic myeloid leukaemia ( CML ) in chronic phase . To test this possibility 587 patients with CML in chronic phase were r and omly allocated to receive lymphoblastoid cell-line interferon-alpha n1 ( IFN-alpha , n = 293 ) or chemotherapy with busulphan or hydroxyurea ( no IFN-alpha , n = 294 ) as maintenance after initial induction treatment with cytotoxic drugs . There was a significant survival benefit for patients in the IFN-alpha arm when analysed on the basis of intention to treat ( 2p = 0.0009 ) . The median survival for those allocated IFN-alpha was 61 months and no IFN-alpha was 41 months . Out of 269 patients with Philadelphia-positive CML in the IFN-alpha arm with at least 6 months follow-up , 211 were evaluable for haematological response : 145 ( 68 % ) achieved good responses ( A+ or A type ) , 37 ( 18 % ) had partial responses ( B type ) and 29 ( 14 % ) had poor responses ( C type ) . Patients with types A and B responses had a better survival than those in the no IFN-alpha arm ; patients with type C responses had survival equivalent to the no IFN-alpha arm . Of these 269 patients , 26 of whom had not started IFN-alpha , 59 ( 22 % ) achieved a significant degree of cytogenetic response but 210 ( 78 % ) did not have a response . Cytogenetic responders survived significantly longer than non-responders and even non-responders survived longer than patients in the no IFN-alpha arm . Since cytogenetic non-responders had worse than average prognostic features , they may also benefit from IFN-alpha therapy . We conclude that treatment with IFN-alpha prolongs the survival of patients with CML ; benefits of IFN-alpha are not confined to cytogenetic responders but may extend to most , if not all patients receiving IFN-alpha treatment ; and cytogenetic response to IFN-alpha treatment identifies patients with a relatively good prognosis While measures of health-related quality of life ( HRQOL ) are increasingly being used as outcomes in clinical trials , it is unknown whether HRQOL assessment s are influenced by the method of administration . We compared telephone , face-to-face , and self-administration of a commonly-used HRQOL measure , the SF-36 . Veterans ( N = 172 ) receiving care in the General Medicine Clinic were r and omized into groups differing only in order of administration . All patients were asked to complete the SF-36 three times over a 4-week period . The SF-36 demonstrated high internal consistency , regardless of mode of administration , but showed large variation over short intervals . This variation may : ( 1 ) increase dramatically sample size requirements to detect between-group differences in r and omized trials and ( 2 ) reduce the SF-36 's usefulness for clinicians wishing to follow individual patients over time Between July 1 , 1981 and November 1 , 1982 , 45 patients with acute nonlymphocytic leukemia ( age , greater than or equal to 70 years ) were r and omly assigned to receive induction chemotherapy using either daunorubicin , cytosine arabinoside , and 6-thioguanine in full dosage ( F DAT ) or an attenuated schedule of the same drugs ( At DAT ) as part of an Eastern Cooperative Oncology Group controlled trial . Forty patients were deemed evaluable , 20 on each arm . The overall complete remission ( CR ) rate for all patients in both arms was 28 % ( 11/40 ) . There was no significant difference in CR rates between the two arms . There were 12 early deaths ( less than 60 days ) in the F DAT arm compared with only five early deaths on the At DAT arm ( P = .05 ) . Due primarily to this early death rate , the median survival for the F DAT group was 29 days v 159 days for the At DAT groups ( P = .02 ) . The range of survival of the patients in CR for the At DAT group given either one or two cycles of induction therapy was 121 to 414 days , while the survival range for the F DAT CR patients was 121 - 186 + days . The median survival for those not achieving CR was 14 days for the F DAT group v 80 days for the At DAT ( P less than .02 ) . Fifty-nine percent of the At DAT patients spent greater than 100 days out of the hospital v 12 % for the F DAT group . Attenuated chemotherapy with lower doses of DAT is the preferred induction regimen for elderly patients with acute nonlymphocytic leukemia since it causes fewer early deaths , allows a better quality of life , and yields survival times as durable as intensive therapy PURPOSE Quality of life ( QOL ) outcomes in patients with chronic myeloid leukemia ( CML ) were evaluated in an international phase III study . PATIENTS AND METHODS Newly diagnosed patients with chronic phase CML were r and omly assigned to imatinib or interferon alfa plus subcutaneous low-dose cytarabine ( IFN+LDAC ) . Cross-over to the other treatment was permitted because of intolerance or lack of efficacy . Patients completed cancer-specific QOL ( Functional Assessment of Cancer Therapy-Biologic Response Modifiers ) and utility ( Euro QoL-5D ) question naires at baseline and during treatment ( n = 1,049 ) . The primary QOL end point was the Trial Outcome Index ( TOI ; a measure of physical function and well-being ) . Secondary end points included social and family well-being ( SFWB ) , emotional well-being ( EWB ) , and the utility score . Primary analyses were intention to treat with secondary analyses accounting for cross-over . RESULTS Patients receiving IFN+LDAC experienced a large decline in the TOI , whereas those receiving imatinib maintained their baseline level . Treatment differences at each visit were significant ( P < .001 ) and clinical ly relevant in favor of imatinib . Mean SFWB , EWB , and utility scores were also significantly better for those patients taking imatinib . Patients who crossed over to imatinib experienced a large increase in TOI ; significant ( P < .001 ) differences were observed between patients who did and did not cross over in favor of imatinib . CONCLUSION Imatinib offers clear QOL advantages compared with IFN+LDAC as first-line treatment of chronic phase CML . In addition , patients who cross over to imatinib from IFN+LDAC experience a significant improvement in QOL compared with patients who continue to take IFN+LDAC OBJECTIVE While health-related quality of life ( HRQOL ) is increasingly being used as an outcome in clinical trials , it is unknown whether HRQOL assessment s are influenced by the method of administration . Within the context of a r and omized , controlled trial evaluating a pharmacist intervention for elderly out patients prescribed at least five medications , we compared telephone and face-to-face administration of the SF-36 , a widely used HRQOL measure . DESIGN Survey . SETTING General Medicine Clinic , Veterans Affairs Medical Center . PATIENTS At entry , participants in the r and omized trial received continuous care from a general medicine clinic physician , were > or = 65 years of age , and were prescribed > or = 5 regularly scheduled medications . Patients were excluded if they were cognitively impaired and had no caregiver available to participate in the study as a proxy or if they resided in a nursing home . MEASUREMENTS Subjects completed the SF-36 by telephone at closeout and face-to-face at clinic visits within 1 month ( mean = 16.7 days ) . MAIN RESULTS Telephone administration required significantly less time than face-to-face interviews ( 10.2 vs 14.0 minutes , P < 0.001 ) . Although systematic differences between modes of administration were generally small , there were substantial non systematic discrepancies for all eight SF-36 scales ( mean absolute difference scores ranged from 10.8 to 30.1 ) . Discrepancies were greatest for emotional role functioning , physical role functioning , social functioning , and bodily pain ; these four scales also demonstrated low to moderate correlations ( .33 to .58 ) . CONCLUSIONS The two modes of administration may not produce interchangeable results . Research ers should be cautious when mixing modes of administration to elderly patients The impact of administration mode on health-related quality of life measurement instruments has received little attention , especially for the SF-36 . General community members were r and omly selected to complete the Australian version of the SF-36 Health Survey using either telephone or mail modes . Modes were compared across a number of indices : data collection costs ; consent rates and non-consent bias ; data quality ( completeness of data and internal consistency reliability ) ; and response effects . Data collection costs were lower for the telephone mode . A significantly higher consent rate was achieved with the telephone mode . Those who were younger were more likely to refuse to participate when the mail mode was adopted , while older people were more likely not to consent to the telephone mode . The rate of missing responses was higher for the mail mode , while significant differences were found between modes in internal consistency reliability estimates . Health ratings were more favorable for the telephone administration . The results are discussed in light of the advantages and disadvantages of each administration mode |
1,210 | 28,432,855 | No evidence of survival benefit was found .
Group programs had the strongest evidence -base for efficacy ; individual and low-intensity therapy had insufficient evidence to form conclusions .
Group interventions had longest intervention duration s and lowest uptake and adherence ; low-intensity interventions had shortest duration s and highest uptake and adherence .
Disparities in uptake , adherence , and reach were evident , with the demographic profile of participants polarised to young , Caucasian , English-speaking , partnered women .
CONCLUSIONS There remains a paucity of psychological interventions for women with metastatic breast cancer .
Those that exist have an inconsistent evidence -base across the range of patient-reported outcomes . | OBJECTIVES To summarise the evidence -base of psychological interventions for women with metastatic breast cancer , by mode of delivery ( group , individual , or low-intensity interventions ) .
To synthesis e data regarding core intervention-elements ( eg , intervention duration ) and context factors ( trial setting , uptake and adherence , and demographic characteristics ) . | BACKGROUND The conduct of r and omized , controlled trials of nonpharmacologic treatments presents specific challenges that are not adequately addressed in trial reports . OBJECTIVE To develop an extension of the CONSORT ( Consoli date d St and ards of Reporting Trials ) Statement for trials of nonpharmacologic treatments . DESIGN A consensus meeting was organized to develop an extension of the CONSORT Statement that addresses r and omized trials of nonpharmacologic treatments . To prepare for the meeting , a survey was conducted to identify the specific issues for discussion . SETTING Consensus meeting in Paris , France . PARTICIPANTS A total of 33 experts attended the meeting . The experts were method ologists ( n = 17 ) ; surgeons ( n = 6 ) ; editors ( n = 5 ) ; and clinicians involved in rehabilitation ( n = 1 ) , psychotherapy ( n = 2 ) , education ( n = 1 ) , and implantable devices ( n = 1 ) . MEASUREMENTS Experts indicated which of the 22 items on the CONSORT checklist should be modified or which additional items should be added specifically for nonpharmacologic treatments . During a 3-day consensus meeting , all items were discussed and additional method ological issues related to nonpharmacologic research were identified . RESULTS The consensus was that 11 items on the CONSORT checklist needed some modifications for nonpharmacologic trials : item 1 ( title and abstract ) , item 3 ( participants ) , item 4 ( interventions ) , item 7 ( sample size ) , item 8 ( r and omization ) , item 11 ( blinding ) , item 12 ( statistical methods ) , item 13 ( participant flow ) , item 15 ( baseline data ) , item 20 ( discussion : interpretation ) , and item 21 ( generalizability ) . In addition , the meeting participants added 1 item related to implementation of the intervention . LIMITATION Evidence was not always available to support the inclusion of each checklist item . CONCLUSION The methods and processes used to develop this extension could be used for other reporting guidelines . The use of this extension to the CONSORT Statement should improve the quality of reporting r and omized , controlled trials assessing nonpharmacologic treatments PURPOSE Early breast cancer survivors ( BCSs ) report high unmet care needs , and easily accessible care is not routinely available for this growing population . The Breast Cancer E-Health ( BREATH ) trial is a Web-based self-management intervention to support the psychological adjustment of women after primary treatment , by reducing distress and improving empowerment . PATIENTS AND METHODS This multicenter , r and omized , controlled , parallel-group trial evaluated whether care as usual ( CAU ) plus BREATH is superior to CAU alone . BREATH is delivered in sixteen fully automated weekly modules covering early survivorship issues . Two to 4 months post-treatment , BCSs were r and omly assigned to receive CAU + BREATH ( n = 70 ) or CAU alone ( n = 80 ) using a stratified block design ( ratio 1:1 ) . Primary outcomes were distress ( Symptom Checklist-90 ) and empowerment ( Cancer Empowerment Question naire ) , assessed before r and om assignment ( baseline , T0 ) and after 4 ( T1 ) , 6 ( T2 ) , and 10 months ( T3 ) of follow-up . Statistical ( analysis of covariance ) and clinical effects ( reliable change index ) were tested in an intention-to-treat analysis ( T0 to T1 ) . Follow-up effects ( T0 to T3 ) were assessed in assessment completers . RESULTS CAU + BREATH participants reported significantly less distress than CAU-alone participants ( -7.79 ; 95 % CI , -14.31 to -1.27 ; P = .02 ) with a small-to-medium effect size ( d = 0.33 ) , but empowerment was not affected ( -1.71 ; 95 % CI , 5.20 to -1.79 ; P = .34 ) . More CAU + BREATH participants ( 39 of 70 [ 56 % ] ; 95 % CI , 44.1 to 66.8 ) than CAU-alone participants ( 32 of 80 [ 40 % ] ; 95 % CI , 30.0 to 51.0 ) showed clinical ly significant improvement ( P = .03 ) . This clinical effect was most prominent in low-distress BCSs . Secondary outcomes confirmed primary outcomes . There were no between-group differences in primary outcomes during follow-up . CONCLUSION Access to BREATH reduced distress among BCSs , but this effect was not sustained during follow-up Background : Internet-based methods for provision of psychological support and intervention to cancer survivors hold promise for increasing the public impact of such treatments . Purpose : The goal of this controlled pilot study was to examine the effect and potential mechanisms of action of a self-guided , Internet-based coping-skills training group on quality of life outcomes in women with early-stage breast cancer . Methods : Sixty-two women completed baseline evaluations and were r and omized into either a small online coping group or a waiting-list control condition . Results : No main effects for treatment were observed at the 12-week follow up . However , there was a significant interaction between baseline self-reported health status and treatment , such that women with poorer self-perceived health status showed greater improvement in perceived health over time when assigned to the treatment condition . Linguistic analyses revealed that positive changes across quality of life variables were associated with greater expression of negative emotions such as sadness and anxiety , greater cognitive processing , and lower expression of health-related concerns . Conclusions : These results demonstrate the potential efficacy of self-guided Internet coping groups while highlighting the limitations of such groups The aims of this study were to ( a ) identify the predictors of attrition from a fully self-directed intervention , and ( b ) to test whether an intervention to increase gratitude is an effective way to reduce body dissatisfaction . Participants ( N=479 , from the United Kingdom ) aged 18 - 76 years took part in a self-help study via the Internet and were r and omized to receive one of two interventions , gratitude diaries ( n=130 ) , or thought monitoring and restructuring ( n=118 ) or a waitlist control ( n=231 ) for a two week body dissatisfaction intervention . The gratitude intervention ( n=40 ) was as effective as monitoring and restructuring ( n=22 ) in reducing body dissatisfaction , and both interventions were significantly more effective than the control condition ( n=120 ) . Participants in the gratitude group were more than twice as likely to complete the intervention compared to those in the monitoring and restructuring group . Intervention content , baseline expectancy and internal locus of control significantly predicted attrition . This study shows that a gratitude intervention can be as effective as a technique commonly used in cognitive therapy and is superior in retaining participants . Prediction of attrition is possible from both intervention content and psychological variables BACKGROUND The aim of this study was to evaluate the short-term effectiveness of the web-based computer-tailored intervention Kanker Nazorg Wijzer ( Cancer Aftercare Guide ) . The intervention aims to support cancer survivors with managing psychosocial and lifestyle-related issues . In this study , the impact on quality of life , anxiety , depression , and fatigue were evaluated . METHODS Cancer survivors were recruited through 21 Dutch hospitals ( November 2013-June 2014 ) . Outcome measures included quality of life ( European Organization for Research and Treatment of Cancer Quality of Life Question naire-C30 ) , anxiety and depression ( Hospital Anxiety and Depression Scale ) , and fatigue ( Checklist Individual Strength ) . In a r and omized controlled trial with an intervention group ( n = 231 ) and a waiting list control group ( n = 231 ) , the short-term effectiveness was evaluated through multilevel linear regression analyses , controlling for selective dropout , baseline differences , and several demographic and disease-related characteristics . RESULTS In total , 188 participants of the intervention group and 221 of the control group completed the 6-month measurement ( dropout = 11.5 % ) . The intervention was effective in reducing depression ( B = -0.63 , p = 0.007 , f2 = 0.019 , d = 0.21 ) and fatigue ( B = -4.36 , p = 0.020 , f2 = 0.013 , d = 0.21 ) . In addition , effects were found for emotional ( B = 3.47 , p = 0.022 , f2 = 0.013 , d = 0.15 ) and social functioning ( B = 3.95 , p = 0.011 , f2 = 0.017 , d = 0.15 ) , although this evidence was less strong . There were indications that the effects of fatigue and social functioning were influenced by module use . CONCLUSIONS While effect sizes were small , they can be considered as clinical ly relevant . With the Cancer Aftercare Guide being an effective , low-intensive , and easy accessible intervention , it could serve as a first step in stepped care for needs assessment and initial support for psychosocial problems that are present after cancer treatment . Copyright © 2016 John Wiley & Sons , Addressing psychosocial and quality of life needs is central to provision of excellent care for people with advanced cancer . This study tested a brief nurse-delivered intervention to address the needs of urban women with advanced breast cancer . This study was conducted at four large urban hospitals in Australia . One hundred and five women with advanced breast cancer were recruited and r and omised to receive the intervention or usual care , then asked to complete the European Organisation of Research and Treatment of Quality of life Q-C30 version ( 2.0 ) ( EORTC Q-C30 ) ( version 2 ) and Supportive Care Needs Survey ( SCNS ) at 1 month and 3 months postrecruitment . No significant differences were detected between intervention and usual care groups in the SCNS or the EORTC Q-C30 subscale scores . However , when the groups were divided into high needs ( score of above 50 ) and low baseline needs ( score of 50 or below ) for each SCNS subscale , a significant difference between intervention and usual care groups was found in the psychological/emotional subscale among women with high baseline needs . In conclusions , this study demonstrated that a face-to-face session and follow-up phone call with a breast care nurse significantly reduced the psychological and emotional needs of those with high initial needs . There was no evidence of the intervention influencing the quality of life ; or perceived needs of women with low initial psychological/emotional needs or perceived needs in other domains . Possibly , the intervention was not sufficiently intense to achieve an effect BACKGROUND Prostate cancer ( PCa ) poses many emotional and physical challenges for men following treatment . The unmet support needs of these men are well documented , and access to psychosocial support remains problematic . OBJECTIVES To assess the efficacy of an online psychological intervention for men who have localised PCa . DESIGN , SETTING , AND PARTICIPANTS We undertook a r and omised controlled trial to evaluate the intervention . Participants were r and omly allocated to one of three conditions : My Road Ahead ( MRA ) alone ( MRA Only ) , MRA plus access to an online forum ( MRA+Forum ) , and access to the forum alone ( Forum ) . INTERVENTION The intervention was a 10-week self-guided online psychological intervention called My Road Ahead that consisted of six themed modules design ed to facilitate improved emotional well-being in the context of PCa as well as a moderated peer forum . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Pre- and postintervention assessment s of psychological distress ( the 21- question Depression , Anxiety and Stress Scale ) [ 1 ] and the Prostate Cancer-related Quality of Life scale [ 2 ] were conducted . Multivariate analysis of variance , regression , and structural equation modelling were used to analyse the data . RESULTS AND LIMITATIONS In total , 142 participants were r and omly allocated to one of the three intervention arms . The mean age of participants was 61 yr of age ( st and ard deviation : 7 ) , and 88 % had undergone radical prostatectomy . A significant improvement in psychological distress was observed for participants who had access to the combined condition ( MRA+Forum ) with a moderate effect size ( p=0.02 ; partial η(2)=0.07 ) . In particular , the decline in the mean level of psychological distress was 8.8 units larger for the MRA+Forum group than the Forum group ( 95 % confidence interval [ CI ] , 0.9 - 16.7 ) . Although the decline in the mean level of psychological distress was 7.0 units larger for the MRA+Forum group than for the MRA Only group , this difference was not significant ( 95 % CI , 1.1 - 15.1 ) . Structural equation modelling indicated that reductions in health worry and regret contributed significantly to the reductions in psychological distress for the MRA+Forum condition . CONCLUSIONS This study is the first , to our knowledge , that has evaluated a self-guided online psychological intervention tailored to the specific needs of men who have PCa . The findings of this study indicate the potential for this programme to deliver support that men may not otherwise receive . PATIENT SUMMARY This study found that men who have localised prostate cancer who received access to the online psychological intervention called My Road Ahead combined with the online peer discussion forum had significantly improved reductions in distress compared with those who received access to the online intervention alone or the forum alone PURPOSE A first breast cancer recurrence creates considerable distress , yet few psychosocial interventions directed at this population have been reported . The Southwest Oncology Group conducted a phase III r and omized trial to evaluate the effectiveness of a brief telephone intervention . PATIENTS AND METHODS Three hundred five women experiencing a first recurrence of breast cancer were r and omly assigned to st and ard care or intervention . The intervention consisted of four to eight telephone calls delivered over a 1-month period . The calls were conducted by trained peer counselors at a breast cancer advocacy organization , the Y-ME National Breast Cancer Organization , and followed a st and ard curriculum . Psychosocial distress ( Cancer Rehabilitation Evaluation System-Short Form [ CARES-SF ] ) and depressive symptoms ( Center for Epidemiologic Studies Depression Scale [ CES-D ] ) outcomes were assessed at baseline and 3 and 6 months . The 3-month assessment was the primary end point and is the focus of this article . RESULTS Analysis revealed no differences in distress or depressive symptoms at 3 months between the intervention and control groups ; at 3 months , 70 % of control patients and 66 % of intervention patients reported psychosocial distress , and 40 % of control patients and 47 % of intervention patients exhibited depressive symptoms . CONCLUSION Telephone peer counseling did not lead to better psychosocial outcomes . The persistent distress in these women supports the urgent need for the development and testing of more intensive or different supportive interventions for this group of patients Purpose This study evaluated the efficacy of a self-guided Web-based cognitive behaviour therapy ( CBT ) intervention compared to an attention control in improving cancer-related distress , health-related quality of life ( HRQOL ) , and maladaptive coping , among people recently diagnosed with cancer . Methods Sixty individuals with cancer diagnosed in the previous 6 months and receiving treatment with curative intent were r and omised to receive either the 6-week intervention Cancer Coping Online ( CCO : n = 30 ) or the 6-week Web-based attention control ( n = 30 ) . Outcome measures , including cancer distress ( the Posttraumatic Stress Scale — Self-Report ) , general distress ( Depression Anxiety Stress Scale ) , quality of life ( EORTC QLQ-C30 ) , and coping ( mini-MAC ) , were administered at baseline , immediately post-intervention , and at 3 and 6 months post-intervention . Results Significant main effects for time were found for cancer distress , global QOL , physical function , role function , social function , and anxious preoccupation . Post hoc between-group comparisons showed CCO participants had statistically significantly higher physical functioning compared to controls at 3 months of follow-up ( d = −0.52 , p = 0.02 ) . Furthermore , compared to controls , post hoc comparisons found moderate between-group effect sizes favouring CCO post-intervention for cancer distress ( d = 0.43 ) and anxious preoccupation ( d = 0.38 ) , and at 6 months of follow-up for global QOL ( d = −0.43 ) . Conclusions These results provide preliminary support for the potential efficacy of a self-guided Web-based CBT programme in improving aspects of HRQOL , cancer-related distress , and anxious preoccupation after cancer diagnosis . This paper provides justification for , and will help inform the development of , subsequent larger multi-site studies Background : Advanced cancer brings substantial physical and psychosocial challenges that may contribute to emotional distress and diminish well-being . In this study , we present preliminary data concerning the effectiveness of a new brief individual psychotherapy , Managing Cancer And Living Meaningfully ( CALM ) , design ed to help individuals cope with this circumstance . Aim : To test the feasibility and preliminary effectiveness of CALM to reduce emotional distress and promote psychological well-being and growth . Design : CALM is a brief , manualized , semi-structured individual psychotherapy for patients with advanced cancer . This study employed a phase 2 intervention-only design . The primary outcome was depressive symptoms and the secondary outcomes were death anxiety , attachment security , spiritual well-being and psychological growth . These were assessed at 3 months ( t1 ) and 6 months ( t2 ) . Multilevel regression was used to model change over time . Setting / participants : A total of 50 patients with advanced or metastatic cancer were recruited from the Princess Margaret Cancer Centre , Toronto , Canada . Results : A total of 39 patients ( 78 % ) were assessed at baseline , 24 ( 48 % ) at t1 , and 16 ( 32 % ) at t2 . Analyses revealed reductions over time in depressive symptoms : beta = −0.13 , confidence interval ( CI.95 ) = ( −0.23 , −0.022 ) and death anxiety : beta = −0.23 , CI.95 ( −0.40 , −0.061 ) ; and an increase in spiritual well-being : beta = 0.14 , CI.95 ( 0.026 , 0.26 ) . Conclusions : CALM may be a feasible intervention to benefit patients with advanced cancer . The results are encouraging , despite attrition and small effect sizes , and support further study The present study was performed to assess the difference in acceptance of psychosocial counseling and result ing benefits between patients with breast cancer with early or late onset . In a prospect i ve r and omized controlled study conducted over 6 months , 41 women with a new diagnosis of early breast cancer ( group 1 ) and 43 patients with advanced breast cancer ( group 2 ) received individually tailored psychosocial support and were compared against controls . This therapy was free of charge , and the duration of support was determined by the patients ' wishes and needs . Among the patients with new onset of disease acceptance of the psychosocial counseling was high , and these patients experienced significant improvements in their quality of life . In contrast , acceptance of psychosocial counseling was low in the advanced breast cancer group and the therapy did not improve quality of life over the observation period of 6 months . Early psychosocial support in patients with breast cancer meets with a high acceptance rate and improves quality of life CONTEXT Not all research presented at scientific meetings is subsequently published and , even when it is , there may be inconsistencies between these results and what is ultimately printed . Although late-breaking trials sessions are now integrated into several major scientific meetings and the results are often promptly and prominently communicated , no studies have examined the publication fate and degree of consistency between meeting abstract s or presentations and subsequent full-length article publications for r and omized controlled trials ( RCTs ) presented at these sessions . OBJECTIVE To compare RCT abstract s presented in the late-breaking trials session vs other sessions at a major scientific meeting and subsequent full-length publications . DESIGN RCTs were identified by h and search ing abstract proceedings booklets and related Web sites for the American College of Cardiology scientific meetings ( 1999 - 2002 ) . Subsequent full-length articles were identified via electronic data bases . MAIN OUTCOME MEASURES Publication fate and degree of consistency between meeting abstract results and subsequent full-length publication results . RESULTS The 86 late-breaking RCTs were significantly larger ( median , 2737 patients vs 896 ; P<.001 ) , were more likely to be preceded by a published design paper ( 27 [ 31 % ] vs 13 [ 13 % ] ; P = .002 ) , had higher quality scores when eventually published ( mean Jadad score 2.69 vs 2.19 ; P = .01 ) , and were less likely to report favorable results for the intervention than the 100 r and omly chosen comparison RCTs presented in other sessions ( 50 [ 58 % ] vs 75 [ 75 % ] ; P = .01 ; odds ratio 0.46 ; 95 % confidence interval , 0.24 - 0.90 ) . RCTs presented at the late-breaking trials sessions were significantly more likely to be published ( 79 [ 92 % ] vs 69 [ 69 % ] ; P<.001 ) and appeared earlier after presentation ( median 11.5 months vs 22.0 months ; P<.001 ) than RCTs presented in other sessions , an association that persisted even after adjusting for sample size , conclusion of study , and RCT design : adjusted hazard ratio , 1.80 ( 95 % confidence interval , 1.24 - 2.61 ) . Sixty ( 41 % ) of the 148 RCTs that were subsequently published exhibited discrepancies between the efficacy estimate reported in the meeting abstract vs the one reported in the full-length article for the primary outcome . The mean change in effect was 0.44 SDs and in 20 cases ( 14 % ) , the point estimate was statistically significant in only 1 member of the pair . The discrepancy rate was the same for late-breaking RCTs as for RCTs presented in other American College of Cardiology sessions ( P = .92 ) . CONCLUSIONS Late-breaking trials were larger , more likely to be preceded by a design paper , and less likely to report positive results than RCTs presented at other sessions , but discrepancies between the meeting abstract results and subsequent full-length publication results were common even for late-breaking trials OBJECTIVES An increasingly important concern for clinicians who care for patients at the end of life is their spiritual well-being and sense of meaning and purpose in life . In response to the need for short-term interventions to address spiritual well-being , we developed Meaning Centered Group Psychotherapy ( MCGP ) to help patients with advanced cancer sustain or enhance a sense of meaning , peace and purpose in their lives , even as they approach the end of life . METHODS Patients with advanced ( stage III or IV ) solid tumor cancers ( N=90 ) were r and omly assigned to either MCGP or a supportive group psychotherapy ( SGP ) . Patients were assessed before and after completing the 8-week intervention , and again 2 months after completion . Outcome assessment included measures of spiritual well-being , meaning , hopelessness , desire for death , optimism/pessimism , anxiety , depression and overall quality of life . RESULTS MCGP result ed in significantly greater improvements in spiritual well-being and a sense of meaning . Treatment gains were even more substantial ( based on effect size estimates ) at the second follow-up assessment . Improvements in anxiety and desire for death were also significant ( and increased over time ) . There was no significant improvement on any of these variables for patients participating in SGP . CONCLUSIONS MCGP appears to be a potentially beneficial intervention for patients ' emotional and spiritual suffering at the end of life . Further research , with larger sample s , is clearly needed to better underst and the potential benefits of this novel intervention The purpose of this pilot study was to examine the effects of a combination of cognitive and behavioral nursing interventions on pain perception , pain control , and mood in metastatic breast cancer patients who were experiencing physical pain . A pretest-posttest experimental research design was utilized in this pilot study . Twenty-four patients with metastatic breast cancer who were experiencing physical pain were r and omly assigned to a control group , to a treatment group who received relaxation and visualization training , or to a treatment group who received relaxation , visualization , and cognitive coping skills training . Measures of the subjects ' pain intensity , pain distress , pain control , ability to decrease pain , and mood were taken pre- and posttreatment . Significant differences were found between the treatment groups and the control group in ability to decrease pain . There were no significant differences found in pain intensity or distress or mood . The results indicate that these cognitive-behavioral interventions could be useful clinical nursing interventions for selected cancer patients experiencing physical pain BACKGROUND Dignity therapy is a unique , individualised , short-term psychotherapy that was developed for patients ( and their families ) living with life-threatening or life-limiting illness . We investigated whether dignity therapy could mitigate distress or bolster the experience in patients nearing the end of their lives . METHODS Patients ( aged ≥18 years ) with a terminal prognosis ( life expectancy ≤6 months ) who were receiving palliative care in a hospital or community setting ( hospice or home ) in Canada , USA , and Australia were r and omly assigned to dignity therapy , client-centred care , or st and ard palliative care in a 1:1:1 ratio . R and omisation was by use of a computer-generated table of r and om numbers in blocks of 30 . Allocation concealment was by use of opaque sealed envelopes . The primary outcomes --reductions in various dimensions of distress before and after completion of the study --were measured with the Functional Assessment of Chronic Illness Therapy Spiritual Well-Being Scale , Patient Dignity Inventory , Hospital Anxiety and Depression Scale , items from the Structured Interview for Symptoms and Concerns , Quality of Life Scale , and modified Edmonton Symptom Assessment Scale . Secondary outcomes of self-reported end-of-life experiences were assessed in a survey that was undertaken after the completion of the study . Outcomes were assessed by research staff with whom the participant had no previous contact to avoid any possible response bias or contamination . Analyses were done on all patients with available data at baseline and at the end of the study intervention . This study is registered with Clinical Trials.gov , number NCT00133965 . FINDINGS 165 of 441 patients were assigned to dignity therapy , 140 st and ard palliative care , and 136 client-centred care . 108 , 111 , and 107 patients , respectively , were analysed . No significant differences were noted in the distress levels before and after completion of the study in the three groups . For the secondary outcomes , patients reported that dignity therapy was significantly more likely than the other two interventions to have been helpful ( χ(2)=35·50 , df=2 ; p<0·0001 ) , improve quality of life ( χ(2)=14·52 ; p=0·001 ) , increase sense of dignity ( χ(2)=12·66 ; p=0·002 ) , change how their family saw and appreciated them ( χ(2)=33·81 ; p<0·0001 ) , and be helpful to their family ( χ(2)=33·86 ; p<0·0001 ) . Dignity therapy was significantly better than client-centred care in improving spiritual wellbeing ( χ(2)=10·35 ; p=0·006 ) , and was significantly better than st and ard palliative care in terms of lessening sadness or depression ( χ(2)=9·38 ; p=0·009 ) ; significantly more patients who had received dignity therapy reported that the study group had been satisfactory , compared with those who received st and ard palliative care ( χ(2)=29·58 ; p<0·0001 ) . INTERPRETATION Although the ability of dignity therapy to mitigate outright distress , such as depression , desire for death or suicidality , has yet to be proven , its benefits in terms of self-reported end-of-life experiences support its clinical application for patients nearing death . FUNDING National Cancer Institute , National Institutes of Health Cognitive behavioral stress management groups have been shown to be decrease psychological symptoms and increase adaptive coping in breast cancer patients , but dissemination of this effective intervention has been challenging . The goal of the present project was to develop an online cognitive behavioral stress management intervention for early stage breast cancer survivors and evaluate its effectiveness using a 2 group × 3 time r and omized , waitlist-controlled design . Intervention and waitlist control group participants were assessed at three time points : at baseline ; at 10 weeks , after which only intervention participants had used the workbook ; and at 20 weeks , after which both groups had used the workbook . Results indicate that at 10 weeks intervention participants showed improved self-efficacy for coping with their cancer and for regulating negative mood and lower levels of cancer-related post-traumatic symptoms as compared to the control group , suggesting that an internet stress management intervention could be effective for helping breast cancer patients increase their confidence in their ability to cope with stress OBJECTIVE This study examined the feasibility and acceptability of an Individual Internet Intervention ( III ) embedded and integrated into an Internet Support Group ( ISG ) with the ultimate goal of enhancing adherence and learning , compared with an individual internet invention alone . METHOD Thirty-one posttreatment cancer survivors were r and omized in groups of seven to nine to either the 8-week III + ISG intervention or the 8-week III condition . Seventeen participants met the Hospital Anxiety and Depression Scale ( HADS ) criteria for depressive symptoms ( HADS ≥ 8) . RESULTS Among all participants , the mean number of logins over 8 weeks was 20.8 ± 17.7 logins for the III + ISG compared with 12.5 ± 12.5 in III-only ( p = 0.15 ) . Two participants in the III + ISG dropped out , compared with five in III ( p = 0.39 ) . Among the 17 participants with depressive symptoms at baseline , both the Onward and the III-only condition showed large reductions in the depression scale of HADS ( d = 1.27 and 0.89 , respectively ) . Improvement over time and time x treatment effects only reached trend significance levels ( ps = 0.07 & 0.12 ) as this pilot was not powered to detect these differences . CONCLUSION Both the III + ISG and III-only demonstrated pre-post reductions in depressive symptoms and high rates of utilization compared with other web-based treatments for depression . Although it is premature to make any determination as to the efficacy of the interventions tested in this feasibility study , these results indicate that pursuing the III + ISG model , as well as st and ard IIIs , may be fruitful areas of future research |
1,211 | 25,414,603 | There may be a short-term pain relief advantage found with the application of corticosteroids , but no demonstrable long-term pain relief .
Injection of botulinum toxin A and prolotherapy are superior to placebo but not to corticosteroids , and botulinum toxin A is likely to produce concomitant extensor weakness .
Platelet-rich plasma or autologous blood injections have been found to be both more and less effective than corticosteroid injections .
Non-invasive treatment methods such as bracing , physical therapy , and extracorporeal shockwave therapy do not appear to provide definitive benefit regarding pain relief .
Some studies of low-level laser therapy show superiority to placebo whereas others do not .
Conclusions There are multiple r and omized controlled trials for non-surgical management of lateral epicondylitis , but the existing literature does not provide conclusive evidence that there is one preferred method of non-surgical treatment for this condition . | Background Non-surgical approaches to treatment of lateral epicondylitis are numerous .
The aim of this systematic review is to examine r and omized , controlled trials of these treatments .
Lateral epicondylitis is a condition that is usually self-limited .
Lateral epicondylitis is a condition that is usually self-limited , resolving over a 12- to 18-month period without treatment . | Background To determine the effectiveness of three different local injection modalities in the treatment of lateral epicondilitis . Methods In a prospect i ve r and omized study on lateral epicondilitis , 75 patients were divided into three equal groups A , B and C ( n = 25 ) and were treated using three different method of local injection . The patients in group A were treated with local injection of a steroid ( 1 mL triamcinolone ) combined with local anaesthetic ( 1 mL lidocaine ) , those in group B were treated with injection of local anaesthetic ( 1 mL lidocaine ) combined with peppering technique and those in group C with local injection of a steroid ( 1 mL triamcinolone ) combined with local anaesthetic ( 1 mL lidocaine ) and peppering technique . The outcome was defined by measuring the elbow pain during the activity using a 10-cm visual analogue scale ( VAS ) and satisfaction with the treatment using a scoring system based on the criteria of the Verhaar et al. at 3 weeks and 6 months after the injection and compared with the pre-treatment condition . Results There were significant ( P = 0.006 ) differences in the successful outcomes between the three groups at 6 months . In group C in which local steroid + peppering injection technique were used ; excellent results were obtained in 84 % of patients comparing to 36 % and 48 % for patients in groups A and B , respectively . The successful outcomes were statistically higher in group C comparing to group A ( P = 0.002 ) and group B ( P = 0.011 ) . In all groups , there was a significantly lower pain ( VAS ) at the 3-week and 6-month follow-ups comparing to the pre-treatment condition . VAS measured at 6-month follow-up were significantly lower in group C comparing to other groups ( P = 0.002 ) . Conclusion In the treatment of lateral epicondilitis , combination of corticosteroid injections with peppering is more effective than corticosteroid injections or peppering injections alone and produces better clinical results Background The aim of this prospect i ve r and omized clinical trial was to investigate the efficacy of a home-based program of isometric strengthening exercises for the treatment of the lateral epicondylitis ( LE ) of the distal humerus . We hypothesized that 1 ) use of isometric strengthening exercises would result in clinical benefits similar to those provided by medication and pain relief and 2 ) functional improvements after exercise would be time-dependent . Methods Patients were assigned to one of two groups : 1 ) an immediate physical therapy group ( group I ) , or 2 ) a delayed physical therapy group ( group D ) . Group I patients ( n = 16 ) were instructed how to do the exercises at their first clinic visit and immediately carried out the exercise program . Group D patients ( n = 15 ) learned and did the exercises after being on medications for 4 weeks . Results Outcomes at the 1-month clinic visit indicated that pain ( measured using a visual analogue scale [ VAS ] ) had been significantly reduced in group I compared to group D ( p < 0.01 ) . However , significant differences between groups were not found at 3- , 6- , and 12-month follow-up for either VAS scores or Mayo elbow performance scores . For modified Nirschl/Pettrone scores , a significant difference between groups was found only at the 1-month follow-up visit . By then , the number of participants who returned to all activities with no pain or occasional mild pain was six ( 37 % ) in Group I and two ( 13 % ) in Group D ( p = 0.031 ) . At the final follow-up visit , 88 % of all participants performed physical activities without pain . Conclusions Isometric strengthening exercises done early in the course of LE ( within 4 weeks ) provides a clinical ly significant improvement & NA ; Forty‐nine patients suffering from lateral humeral epicondylalgia were enrolled in a double‐blind study to observe the effects of Ga‐As laser applied to acupuncture points . The Mid 1500 IRRADIA laser machine was used , wavelength : 904 nm , mean power output : 12 mW , peak value : 8.3 W ; frequency : 70 Hz ( pulse train ) . Localization of points : LI 10 , 11 , 12 , Lu 5 and SJ 5 . Each point was treated for 30 sec result ing in a dose of treatment of 0.36 J/point . The patients were treated 2–3 times weekly with 10 treatments in all . Follow‐ups were done after 3 months and 1 year . No significant differences were observed between the laser and the placebo group in relation to the subjective or objective outcome after 10 treatments or at the follow‐ups Kazemi M , Azma K , Tavana B , Rezaiee Moghaddam F , Panahi A : Autologous blood versus corticosteroid local injection in the short-term treatment of lateral elbow tendinopathy : A r and omized clinical trial of efficacy . Objective : To compare local corticosteroid with autologous blood injections for the short-term treatment of lateral elbow tendinopathy . Design : A single blind , r and omized clinical trial was performed in an outpatient clinic at a university hospital . Sixty patients aged 27–64 yrs with a new episode of tennis elbow were recruited . Thirty patients were r and omized to methylprednisolone and 30 to autologous blood group over 1 yr . Severity of pain within last 24 hrs ; limb function ; pain and strength in maximum grip ; disabilities of the arm , shoulder , and h and quick question naire ( Quick DASH ) scores ; modified Nirschl scores ; and pressure pain threshold were evaluated before injection and at 4 and 8 wks after injection . We analyzed our data with the & khgr;2 and t test . Results : Within-group analyses showed better results for autologous blood ( all P values < 0.001 except for grip strength , P = 0.005 ) . In the corticosteroid group , differences in severity of pain ( P = 0.008 ) and grip strength ( P = 0.001 ) were significant . At 4 wks , between-group analyses showed superiority of autologous blood for severity of pain ( P = 0.001 ) , pain in grip ( P = 0.002 ) , pressure pain threshold ( P = 0.031 ) , and Quick DASH question naire score ( P = 0.004 ) . There were no significant differences in modified Nirschl score , grip strength , and limb function . At 8 wks , autologous blood was more effective in all the outcomes ( all P values < 0.001 ) . Conclusions : Autologous blood was more effective in short term than the corticosteroid injection Background There is conflicting evidence regarding extracorporeal shock wave treatment for chronic tennis elbow . Hypothesis Treatment with repetitive low-energy extracorporeal shock wave treatment is superior to repetitive placebo extracorporeal shock wave treatment . Methods Seventy-eight patients enrolled in a placebo-controlled trial . All patients were tennis players with recalcitrant MRIconfirmed tennis elbow of at least 12 months ’ duration . Patients were r and omly assigned to receive either active low-energy extracorporeal shock wave treatment given weekly for 3 weeks ( treatment group 1 ) or an identical placebo extracorporeal shock wave treatment ( sham group 2 ) . Main outcome measure was pain during resisted wrist extension at 3 months ; secondary measures were > 50 % reduction of pain and the Upper Extremity Function Scale . Results At 3 months , there was a significantly higher improvement in pain during resisted wrist extension in group 1 than in group 2 ( mean [ SD ] improvement , 3.5 [ 2.0 ] and 2.0 [ 1.9 ] ; P= .001 for between-group difference of improvement ) and in the Upper Extremity Function Scale ( mean [ SD ] improvement , 23.4 [ 14.8 ] and 10.9 [ 14.9 ] ; P < .001 for between-group difference of improvement ) . In the treatment group , 65 % of patients achieved at least a 50 % reduction of pain , compared with 28 % of patients in the sham group ( P= .001 for between-group difference ) . Conclusion Low-energy extracorporeal shock wave treatment as applied is superior to sham treatment for tennis elbow Abstract Objective To investigate the efficacy of physiotherapy compared with a wait and see approach or corticosteroid injections over 52 weeks in tennis elbow . Design Single blind r and omised controlled trial . Setting Community setting , Brisbane , Australia . Participants 198 participants aged 18 to 65 years with a clinical diagnosis of tennis elbow of a minimum six weeks ' duration , who had not received any other active treatment by a health practitioner in the previous six months . Interventions Eight sessions of physiotherapy ; corticosteroid injections ; or wait and see . Main outcome measures Global improvement , grip force , and assessor 's rating of severity measured at baseline , six weeks , and 52 weeks . Results Corticosteroid injection showed significantly better effects at six weeks but with high recurrence rates thereafter ( 47/65 of successes subsequently regressed ) and significantly poorer outcomes in the long term compared with physiotherapy . Physiotherapy was superior to wait and see in the short term ; no difference was seen at 52 weeks , when most participants in both groups reported a successful outcome . Participants who had physiotherapy sought less additional treatment , such as non-steroidal anti-inflammatory drugs , than did participants who had wait and see or injections . Conclusion Physiotherapy combining elbow manipulation and exercise has a superior benefit to wait and see in the first six weeks and to corticosteroid injections after six weeks , providing a reasonable alternative to injections in the mid to long term . The significant short term benefits of corticosteroid injection are paradoxically reversed after six weeks , with high recurrence rates , implying that this treatment should be used with caution in the management of tennis elbow OBJECTIVE The aim of this study was to evaluate the effectiveness of 904-nm low-level laser therapy ( LLLT ) in the management of lateral epicondylitis . BACKGROUND DATA Lateral epicondylitis is characterized by pain and tenderness over the lateral elbow , which may also result in reduction in grip strength and impairment in physical function . LLLT has been shown effective in its therapeutic effects in tissue healing and pain control . METHODS Thirty-nine patients with lateral epicondylitis were r and omly assigned to receive either active laser with an energy dose of 0.275 J per tender point ( laser group ) or sham irradiation ( placebo group ) for a total of nine sessions . The outcome measures were mechanical pain threshold , maximum grip strength , level of pain at maximum grip strength as measured by the Visual Analogue Scale ( VAS ) and the subjective rating of physical function with Disabilities of the Arm , Shoulder and H and ( DASH ) question naire . RESULTS Significantly greater improvements were shown in all outcome measures with the laser group than with the placebo group ( p < 0.0125 ) , except in the two subsections of DASH . CONCLUSION This study revealed that LLLT in addition to exercise is effective in relieving pain , and in improving the grip strength and subjective rating of physical function of patients with lateral epicondylitis Background : Chronic lateral elbow epicondylitis is a tendinosis with angiofibrolastic degeneration of the wrist extensors ’ origin . Healing of this lesion is reported with the use of autologous blood as well as with platelet-rich plasma ( PRP ) . Purpose : A comparative study of these 2 treatments was conducted in an effort to investigate the possible advantages of PRP . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : Twenty-eight patients were divided equally into 2 groups , after blocked r and omization . Group A was treated with a single injection of 3 mL of autologous blood and group B with 3 mL of PRP under ultrasound guidance . A st and ardized program of eccentric muscle strengthening was followed by all patients in both groups . Evaluation using a pain visual analog scale ( VAS ) and Liverpool elbow score was performed at 6 weeks , 3 months , and 6 months . Results : The VAS score improvement was larger in group B at every follow-up interval but the difference was statistically significant only at 6 weeks , when mean improvement was 3.8 points ( 95 % confidence interval [ CI ] , 3.1 - 4.5 ) in group B ( 61.47 % improvement ) and 2.5 points ( 95 % CI , 1.9 - 3.1 ) in group A ( 41.6 % improvement ) ( P < .05 ) . No statistically significant difference was noted between groups regarding Liverpool elbow score . Conclusion : Regarding pain reduction , PRP treatment seems to be an effective treatment for chronic lateral elbow epicondylitis and superior to autologous blood in the short term . Defining details of indications , best PRP concentration , number and time of injections , as well as rehabilitation protocol might increase the method ’s effectiveness . Additionally , the possibility of cost reduction of the method might justify the use of PRP over autologous whole blood for chronic or refractory tennis elbow Abstract Background . Chronic tennis elbow ( lateral epicondylosis ) is a common disorder . Like other chronic soft-tissue pain conditions it is often difficult to treat successfully . The effects of exercise have been discussed , but no convincing evidence has been put forward so far , and a simple protocol for exercise is lacking . Aims of the study . This study is a r and omized , controlled , clinical trial of the effect of exercise versus expectation ( wait-list ) on pain , muscle strength , function , and quality of life in patients with long-st and ing lateral epicondylosis . Methods . Eighty-one subjects with tennis elbow lasting for more than 3 months were r and omly allocated to an exercise group ( n = 40 ) or a reference group ( n = 41 ) . The exercise group performed daily exercise , with weekly load increase , for 3 months . The reference group was wait-listed , but otherwise followed in the same way . Outcome measures were pain during maximum voluntary muscle contraction ( Cozen 's test ) and pain during maximum muscle elongation with a load ( modified Empty-can-test ) ; muscle strength was measured with a Chatillon MSE 100 h and -held dynamometer , and the Disability of the Arm , Shoulder and H and ( DASH ) and the Gothenburg Quality of Life question naires . Results . The exercise group had greater and faster regression of pain , both during muscle contraction and muscle elongation , than the reference group ( p = 0.0005 and p = 0.0016 , respectively ) . There was a non-significant muscle strength difference between the groups , but no differences regarding DASH scores or quality of life measures . Conclusions . Exercise appears to be superior to expectation in reducing pain in chronic lateral epicondylosis OBJECTIVE This study was undertaken to compare the effectiveness of a protocol of combination of laser with plyometric exercises and a protocol of placebo laser with the same program , in the treatment of tennis elbow . BACKGROUND DATA The use of low-level laser has been recommended for the management of tennis elbow with contradictory results . Also , plyometric exercises was recommended for the treatment of the tendinopathy . METHODS Fifty patients who had tennis elbow participated in the study and were r and omised into two groups . Group A ( n = 25 ) was treated with a 904 Ga-As laser CW , frequency 50 Hz , intensity 40 mW and energy density 2.4 J/cm(2 ) , plus plyometric exercises and group B ( n = 25 ) that received placebo laser plus the same plyometric exercises . During eight weeks of treatment , the patients of the two groups received 12 sessions of laser or placebo , two sessions per week ( weeks 1 - 4 ) and one session per week ( weeks 5 - 8 ) . Pain at rest , at palpation on the lateral epicondyle , during resisted wrist extension , middle finger test , and strength testing was evaluated using Visual Analogue Scales . Also it was evaluated the grip strength , the range of motion and weight test . Parameters were determined before the treatment , at the end of the eighth week course of treatment ( week 8) , and eighth ( week 8) after the end of treatment . RESULTS Relative to the group B , the group A had ( 1 ) a significant decrease of pain at rest at the end of 8 weeks of the treatment ( p < 0.005 ) and at the end of following up period ( p < 0.05 ) , ( 2 ) a significant decrease in pain at palpation and pain on isometric testing at 8 weeks of treatment ( p < 0.05 ) , and at 8 weeks follow-up ( p < 0.001 ) , ( 3 ) a significant decrease in pain during middle finger test at the end of 8 weeks of treatment ( p < 0.01 ) , and at the end of the follow-up period ( p < 0.05 ) , ( 4 ) a significant decrease of pain during grip strength testing at 8 weeks of treatment ( p < 0.05 ) , and at 8 weeks follow-up ( p < 0.001 ) , ( 5 ) a significant increase in the wrist range of motion at 8 weeks follow-up ( p < 0.01 ) , ( 6 ) an increase in grip strength at 8 weeks of treatment ( p < 0.05 ) and at 8 weeks follow-up ( p < 0.01 ) , and ( 7 ) a significant increase in weight-test at 8 weeks of treatment ( p < 0.05 ) and at 8 weeks follow-up ( p < 0.005 ) . CONCLUSION The results suggested that the combination of laser with plyometric exercises was more effective treatment than placebo laser with the same plyometric exercises at the end of the treatment as well as at the follow-up . Future studies are needed to establish the relative and absolute effectiveness of the above protocol We investigated the effectiveness of braces in the treatment of lateral epicondylitis and compared the effects of two different types of most frequently used braces . A total of 50 patients ( seven males and 43 females ) with an age range of 34 to 60 who had the diagnosis of lateral epicondylitis were included in the study . The patients were distributed into two groups . In group I , 25 patients ( 21 females and four males ) were given a lateral epicondyle b and age . In group II , 25 patients ( 22 females and three males ) were given a wrist resting splint holding the wrist in slight dorsiflexion . Evaluations of the patients were done before treatment and at the second and sixth weeks of treatment . Evaluation parameters were pain during rest and movement , sensitivity , algometer score , h and grip strength , and evaluation of the response to treatment . The response to treatment was evaluated according to the following categories : excellent , good , medium , and bad . In group I , only pain during rest and movement significantly decreased at 2 weeks while significant improvement was obtained for all parameters at 6 weeks . In group II , all parameters except for algometric sensitivity showed significant improvement at 2 weeks . Significant improvement was obtained for all parameters at 6 weeks in this group . Comparison of the two groups showed significantly better improvement in resting pain in group II at 2 weeks while there was no difference for other parameters including response to treatment at either evaluation stage . Braces might be a good strategy to help wait out the natural course of tennis elbow complaints . Although epicondyle b and age was not found to be superior to wrist splint in our study , we may suggest that it could be favored over splint since it is more practical and cosmetically acceptable OBJECTIVE To compare the efficacy of prolotherapy versus corticosteroid injection for the treatment of chronic lateral epicondylosis . DESIGN A prospect i ve , r and omized controlled , double-blinded study . SETTING Academic , tertiary , outpatient , rehabilitation hospital . PARTICIPANTS Twenty-four subjects with clinical ly determined chronic ( ie , lasting 3 months or longer ) lateral epicondylosis were recruited . All subjects noted pain intensity levels significant enough to prevent the participation in activities , such as playing racquet sports or lifting heavy objects . METHODS Subjects were assigned to receive either prolotherapy or corticosteroid injection for treatment of chronic lateral epicondylosis . Each subject underwent injection at baseline followed by a second injection 1 month later . OUTCOME MEASUREMENTS Visual analog scale ( VAS ) self-rating of pain , quadruple visual analog scale ( QVAS ) , and the Disabilities of the Arm , Shoulder , and H and question naire ( DASH ) were measured at baseline and at 1 , 3 , and 6 months ' follow-up . RESULTS Within each group , the analysis demonstrated statistically significant improvements in both VAS and DASH within the prolotherapy group with significant changes noted from baseline to 3 months ( VAS : Δ2.38 ; 95 % confidence interval [ 95 % CI ] 1.04 - 3.71 , P = .004 and DASH : Δ19.89 ; 95 % CI 5.73 - 34.04 , P = .01 ) , and baseline to 6 months ( VAS : Δ2.63 ; 95 % CI 0.61 - 4.62 , P = .017 and DASH : Δ21.76 ; 9 % CI 7.43 - 36.09 , P = .009 ) after initial treatment , as well as in the QVAS from baseline to 3 months . The steroid group demonstrated a clinical ly and statistically significant change for DASH only at both 3-month ( Δ13.33 ; 95 % CI 0.68 - 25.99 , P = .04 ) and 6-month ( Δ15.56 ; 95 % CI 1.30 - 29.81 , P = .04 ) follow-up . Comparison of the subjects completing the study revealed no significant differences between the prolotherapy and the corticosteroid group for change in VAS , QVAS , or DASH , although the study lacked sufficient power to draw conclusions from this finding . Eighty-three percent of the subjects were satisfied with their overall improvement during the course of the study , without significant differences revealed between groups . Aside from injection-associated pain , no adverse reactions were reported . Seventeen subjects completed study protocol . CONCLUSIONS Both prolotherapy and corticosteroid therapy were generally well tolerated and appeared to provide benefit of long duration . Small sample size precludes determining whether one therapy is superior to the other . Larger , controlled trials appear feasible and warranted on the basis of these findings Abstract Objective : To compare the clinical effectiveness of local corticosteroid injection , st and ard non-steroidal anti-inflammatory drugs , and simple analgesics for the early treatment of lateral epicondylitis in primary care . Design : Multicentre pragmatic r and omised controlled trial . Setting : 23 general practice s in North Staffordshire and South Cheshire . Participants : 164 patients aged 18 - 70 years presenting with a new episode of lateral epicondylitis . Interventions : Local injection of 20 mg methylprednisolone plus lignocaine , naproxen 500 mg twice daily for two weeks , or placebo tablets . All participants received a st and ard advice sheet and co-codamol as required . Main outcome measures : Participants ' global assessment of improvement ( five point scale ) at four weeks . Pain , function , and “ main complaint ” measured on 10 point Likert scales at 4 weeks , 6 months , and 12 months . Results : Over 2 years , 53 subjects were r and omised to injection , 53 to naproxen , and 58 to placebo . Prognostic variables were similar between groups at baseline . At 4 weeks , 48 patients ( 92 % ) in the injection group were completely better or improved compared with 30 ( 57 % ) in the naproxen group ( P<0.001 ) and 28 ( 50 % ) in the placebo group ( P<0.001 ) . At 12 months , 43 patients ( 84 % ) in the injection group had pain scores ≤3 compared with 45 ( 85 % ) in the naproxen group and 44 ( 82 % ) in the placebo group ( P>0.05 ) . Conclusions : Early local corticosteroid injection is effective for lateral epicondylitis . Outcome at one year was good in all groups , and effective early treatment does not seem to influence this . Key messages Most lateral epicondylitis is managed by general practitioners , but optimum treatment is unclear This large pragmatic r and omised trial showed that corticosteroid injection was significantly better than non-steroidal anti-inflammatories or placebo tablets at four weeks A two week course of a st and ard non-steroidal anti-inflammatory was no better than placebo A few patients who respond well initially to injection relapse by six months . Long term outcome was good , irrespective of initial treatment Background : Platelet-rich plasma ( PRP ) has been shown to be a general stimulation for repair and 1-year results showed promising success percentages . Purpose : This trial was undertaken to determine the effectiveness of PRP compared with corticosteroid injections in patients with chronic lateral epicondylitis with a 2-year follow-up . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : The trial was conducted in 2 Dutch teaching hospitals . One hundred patients with chronic lateral epicondylitis were r and omly assigned to a leukocyte-enriched PRP group ( n = 51 ) or the corticosteroid group ( n = 49 ) . R and omization and allocation to the trial group were carried out by a central computer system . Patients received either a corticosteroid injection or an autologous platelet concentrate injection through a peppering needling technique . The primary analysis included visual analog scale ( VAS ) pain scores and Disabilities of the Arm , Shoulder and H and ( DASH ) outcome scores . Results : The PRP group was more often successfully treated than the corticosteroid group ( P < .0001 ) . Success was defined as a reduction of 25 % on VAS or DASH scores without a reintervention after 2 years . When baseline VAS and DASH scores were compared with the scores at 2-year follow-up , both groups significantly improved across time ( intention-to-treat principle ) . However , the DASH scores of the corticosteroid group returned to baseline levels , while those of the PRP group significantly improved ( as-treated principle ) . There were no complications related to the use of PRP . Conclusion : Treatment of patients with chronic lateral epicondylitis with PRP reduces pain and increases function significantly , exceeding the effect of corticosteroid injection even after a follow-up of 2 years . Future decisions for application of PRP for lateral epicondylitis should be confirmed by further follow-up from this trial and should take into account possible costs and harms as well as benefits BACKGROUND The use of extracorporeal shock wave therapy for the treatment of lateral epicondylitis is controversial . The purpose of this study was to evaluate the use of extracorporeal shock wave therapy without local anesthesia to treat chronic lateral epicondylitis . METHODS One hundred and fourteen patients with a minimum six-month history of lateral epicondylitis that was unresponsive to conventional therapy were r and omized into double-blind active treatment and placebo groups . The protocol consisted of three weekly treatments of either low-dose shock wave therapy without anesthetic or a sham treatment . Patients had a physical examination , including provocation testing and dynamometry , at one , four , eight , and twelve weeks and at six and twelve months after treatment . Radiographs , laboratory studies , and electrocardiograms were also evaluated prior to participation and at twelve weeks . A visual analog scale was used to evaluate pain , and an upper extremity functional scale was used to assess function . Crossover to active treatment was initiated for nonresponsive patients who had received the placebo and met the inclusion criteria after twelve weeks . RESULTS A total of 108 of the 114 r and omized patients completed all treatments and the twelve weeks of follow-up required by the protocol . Sixty-one patients completed one year of follow-up , whereas thirty-four patients crossed over to receive active treatment . A significant difference ( p = 0.001 ) in pain reduction was observed at twelve weeks in the intent-to-treat cohort , with an improvement in the pain score of at least 50 % seen in 61 % ( thirty-four ) of the fifty-six patients in the active treatment group who were treated according to protocol compared with 29 % ( seventeen ) of the fifty-eight subjects in the placebo group . This improvement persisted in those followed to one year . Functional activity scores , activity-specific evaluation , and the overall impression of the disease state all showed significant improvement as well ( p < 0.05 ) . Crossover patients also showed significant improvement after twelve weeks of active treatment , with 56 % ( nineteen of thirty-four ) achieving an improvement in the pain score of at least 50 % ( p < 0.0001 ) . CONCLUSIONS These results demonstrate that low-dose shock wave therapy without anesthetic is a safe and effective treatment for chronic lateral epicondylitis Objectives : To assess whether prolotherapy , an injection-based therapy , improves elbow pain , grip strength , and extension strength in patients with lateral epicondylosis . Setting : Outpatient Sport Medicine clinic . Study Design : Double-blind r and omized controlled trial . Participants : Twenty-four adults with at least 6 months of refractory lateral epicondylosis . Intervention : Prolotherapy participants received injections of a solution made from 1 part 5 % sodium morrhuate , 1.5 parts 50 % dextrose , 0.5 parts 4 % lidocaine , 0.5 parts 0.5 % sensorcaine and 3.5 parts normal saline . Controls received injections of 0.9 % saline . Three 0.5-mL injections were made at the supracondylar ridge , lateral epicondyle , and annular ligament at baseline and at 4 and 8 weeks . Outcome Measures : The primary outcome was resting elbow pain ( 0 to 10 Likert scale ) . Secondary outcomes were extension and grip strength . Each was performed at baseline and at 8 and 16 weeks . One-year follow-up included pain assessment and effect of pain on activities of daily living . Results : The groups were similar at baseline . Compared to Controls , Prolotherapy subjects reported improved pain scores ( 4.5 ± 1.7 , 3.6 ± 1.2 , and 3.5 ± 1.5 versus 5.1 ± 0.8 , 3.3 ± 0.9 , and 0.5 ± 0.4 at baseline and at 8 and 16 weeks , respectively ) . At 16 weeks , these differences were significant compared to baseline scores within and among groups ( P < 0.001 ) . Prolotherapy subjects also reported improved extension strength compared to Controls ( P < 0.01 ) and improved grip strength compared to baseline ( P < 0.05 ) . Clinical improvement in Prolotherapy group subjects was maintained at 52 weeks . There were no adverse events . Conclusions : Prolotherapy with dextrose and sodium morrhuate was well tolerated , effectively decreased elbow pain , and improved strength testing in subjects with refractory lateral epicondylosis compared to Control group injections Objective . To compare the effectiveness of supervised exercise program and Cyriax physiotherapy in the treatment of tennis elbow ( lateral epicondylitis ) . Design . R and omized clinical trial . Setting . Physiotherapy and rehabilitation centre . Subjects . This study was carried out with 20 patients , who had tennis elbow ( lateral epicondylitis ) . Intervention . Group A ( n = 10 ) had received supervised exercise program . Group B ( n = 10 ) was treated with Cyriax physiotherapy . All patients received three treatment sessions per week for four weeks ( 12 treatment sessions ) . Outcome measures . Pain was evaluated using a visual analogue scale ( VAS ) , and functional status was evaluated by completion of the Tennis Elbow Function Scale ( TEFS ) which were recorded at base line and at the end of fourth week . Results . Both the supervised exercise program and Cyriax physiotherapy were found to be significantly effective in reduction of pain and in the improvement of functional status . The supervised exercise programme result ed in greater improvement in comparison to those who received Cyriax physiotherapy . Conclusion . The results of this clinical trial demonstrate that the supervised exercise program may be the first treatment choice for therapist in managing tennis elbow Background : A better treatment modality is needed to control the pain of medial or lateral epicondylitis ( tennis elbow ) . Hypothesis : Dermal iontophoretic administration of dexamethasone sodium phosphate will be significantly more effective in controlling pain than a placebo in patients with medial or lateral elbow epicondylitis . Study Design : R and omized , double-blinded , placebo-controlled study . Methods : On six occasions , 1 to 3 days apart within 15 days , 199 patients with elbow epicondylitis received 40 mA-minutes of either active or placebo treatment . Results : Dexamethasone produced a significant 23-mm improvement on the 100-mm patient visual analog scale ratings , compared with 14 mm for placebo at 2 days and 24 mm compared with 19 mm at 1 month . More patients treated with dexamethasone than those treated with placebo scored moderate or better on the investigator 's global improvement scale ( 52 % versus 33 % ) at 2 days , but the difference was not significant at 1 month ( 54 % versus 49 % ) . Investigator-rated pain and tenderness scores favored dexamethasone over placebo at 2 days . Patients completing six treatments in 10 days or less had better results than those treated over a longer period . Conclusions : Iontophoresis treatment was well tolerated by most patients and was effective in reducing symptoms of epicondylitis at short-term follow-up Background : Lateral epicondylitis ( LE ) is a common musculoskeletal disorder for which an effective treatment strategy remains unknown . Purpose : To examine whether a single injection of platelet-rich plasma ( PRP ) is more effective than placebo ( saline ) or glucocorticoid in reducing pain in adults with LE after 3 months . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : A total of 60 patients with chronic LE were r and omized ( 1:1:1 ) to receive either a blinded injection of PRP , saline , or glucocorticoid . The primary end point was a change in pain using the Patient-Rated Tennis Elbow Evaluation ( PRTEE ) question naire at 3 months . Secondary outcomes were ultrasonographic changes in tendon thickness and color Doppler activity . Results : Pain reduction at 3 months ( primary end point ) was observed in all 3 groups , with no statistically significant difference between the groups ; mean differences were the following : glucocorticoid versus saline : −3.8 ( 95 % CI , −9.9 to 2.4 ) ; PRP versus saline : −2.7 ( 95 % CI , −8.8 to 3.5 ) ; and glucocorticoid versus PRP : −1.1 ( 95 % CI , −7.2 to 5.0 ) . At 1 month , however , glucocorticoid reduced pain more effectively than did both saline and PRP ; mean differences were the following : glucocorticoid versus saline : −8.1 ( 95 % CI , −14.3 to −1.9 ) ; and glucocorticoid versus PRP : −9.3 ( 95 % CI , −15.4 to −3.2 ) . Among the secondary outcomes , at 3 months , glucocorticoid was more effective than PRP and saline in reducing color Doppler activity and tendon thickness . For color Doppler activity , mean differences were the following : glucocorticoid versus PRP : −2.6 ( 95 % CI , −3.1 to −2.2 ) ; and glucocorticoid versus saline : −2.0 ( 95 % CI , −2.5 to −1.6 ) . For tendon thickness , mean differences were the following : glucocorticoid versus PRP : −0.5 ( 95 % CI , −0.8 to −0.2 ) ; and glucocorticoid versus saline : −0.8 ( 95 % CI , −1.2 to −0.5 ) . Conclusion : Neither injection of PRP nor glucocorticoid was superior to saline with regard to pain reduction in LE at the primary end point at 3 months . However , injection of glucocorticoid had a short-term pain-reducing effect at 1 month in contrast to the other therapies . Injection of glucocorticoid in LE reduces both color Doppler activity and tendon thickness compared with PRP and saline PURPOSE We compared saline , corticosteroid , and autologous blood injections for lateral epicondylitis in a prospect i ve , blinded , r and omized , controlled trial . The null hypothesis was that patient-rated outcomes after autologous blood injection would not be superior to corticosteroid and saline injections . METHODS Patients with clinical ly diagnosed lateral epicondylitis of less than 6 months ' duration were r and omized into 1 of 3 groups to receive a 3-mL injection of saline and lidocaine , corticosteroid and lidocaine , or autologous blood and lidocaine . Of 34 subjects who enrolled , 28 completed follow-up . A total of 10 were r and omized to the saline group , 9 to the autologous blood group , and 9 to the steroid group . Every participant had 3 mL blood drawn , and the injection syringe was foil-covered to prevent the subject from knowing the contents . The primary outcome measure was the Disabilities of the Arm , Shoulder , and H and ( DASH ) score . Patients completed a pain visual analog scale , DASH , and the Patient-Rated Forearm Evaluation before injection and at 2 weeks , 2 months , and 6 months after injection . We performed statistical analysis using repeated measures of analyses of variance . RESULTS There were no significant differences in DASH scores among the 3 groups at 2- and 6-month follow-up points , with the mean scores for saline at 20 and 10 , respectively , compared with 28 and 20 for autologous blood and 28 and 13 for steroid injections . Secondary measures showed similar findings , with outcomes scores showing improvement in all 3 groups . CONCLUSIONS In this prospect i ve , r and omized , controlled trial , autologous blood , corticosteroid , and saline injection provide no advantage over placebo saline injections in the treatment of lateral epicondylitis . Patients within each injection group demonstrated improved outcome scores over a 6-month period We performed a prospect i ve , r and omised trial on 106 patients to compare the effects of local corticosteroid injections with physiotherapy as advocated by Cyriax in the treatment of tennis elbow . The main outcome measures were the severity of pain , pain provoked by resisted dorsiflexion of the wrist , and patient satisfaction . At six weeks 22 of 53 patients in the injection group were free from pain compared with only three in the physiotherapy group . In the corticosteroid-treated group 26 patients had no pain on resisted dorsiflexion of the wrist compared with only three in the physiotherapy group . Thirty-five patients who had injections and 14 who had physiotherapy were satisfied with the outcome of treatment at six weeks . At the final assessment there were 18 excellent and 18 good results in the corticosteroid group and one excellent and 12 good results in the physiotherapy group . There was a significant increase in grip strength in both groups but those with injections had a significantly better result . After one year there were no significant differences between the two groups . Half of the patients , however , had received only the initial treatment , 20 % had had combined therapy and 30 % had had surgery . We conclude that at six weeks , treatment with corticosteroid injections was more effective than Cyriax physiotherapy and we recommend it because of its rapid action , reduction of pain and absence of side-effects Lin Y-C , Tu Y-K , Chen S-C , Chen S-S , Lin I-L , Guo H-R : Comparison between botulinum toxin and corticosteroid injection in the treatment of acute and subacute tennis elbow : A prospect i ve , r and omized , double-blind , active drug-controlled pilot study . Objective : To compare botulinum toxin type A injection with corticosteroid injection in the treatment of tennis elbow . Design : In this prospect i ve , r and omized , double-blind , drug-controlled trial,19 affected elbows of 16 patients were r and omly assigned to receive injection with botulinum toxin type A ( Botox group ) or triamcinolone acetonide ( steroid group ) . We used the Visual Analog Scale , pain-free grip strength , and World Health Organization Quality of Life Brief Question naire to assess the perception of pain , grip strength , and quality of life , respectively . Measures were performed before and at 4 , 8 , and 12 wks after the treatment . Results : Four weeks after the treatment , the Botox group had smaller decrease in pain ( P = 0.02 ) but greater decrease in grip strength ( P = 0.01 ) . The difference in grip strength remained significant at 8 wks ( P = 0.03 ) . No significant differences in quality of life were observed throughout the study period . Conclusions : Corticosteroid is superior to botulinum toxin type A in relieving pain in tennis elbow at 4 wks after injection . Because botulinum toxin injection did not relieve pain significantly but is associated with weakness , the muscle weakness caused by botulinum toxin is unlikely to be the sole mechanism of the pain relief observed in previous studies BACKGROUND A recent report has suggested that local injection of botulinum toxin type A is an effective method of treatment for chronic tennis elbow . The toxin is thought to provide temporary paralysis of the painful common extensor origin , thereby allowing a healing response to occur . To test this theory , we performed a double-blind , r and omized , controlled , pilot trial comparing injections of botulinum toxin type A with those of a placebo ( normal saline solution ) in the treatment of chronic tennis elbow . METHODS Forty patients with a history of chronic tennis elbow for which all conservative treatment measures , including steroid injection , had failed were r and omized into two groups . Half the patients received 50 units of botulinum toxin type A , and the remainder received normal saline solution . The intramuscular injections were performed 5 cm distal to the maximum point of tenderness at the lateral epicondyle , in line with the middle of the wrist . The two solutions used for the injections were identical in appearance and temperature . The results of a quality -of-life assessment with the Short Form-12 ( SF-12 ) , the pain score on a visual analogue scale , and the grip strength measured with a vali date d Jamar dynamometer were recorded before and three months after the injection . RESULTS Three months following the injections , there was no significant difference between the two groups with regard to grip strength , pain , or quality of life . CONCLUSIONS With the numbers studied , we failed to find a significant difference between the two groups ; thus , we have no evidence of a benefit from botulinum toxin injection in the treatment of chronic tennis elbow The objective of this prospect i ve r and omised study was to analyse the effect of the forearm support b and and of strengthening exercises for the treatment of tennis elbow . Twenty-nine patients with 30 tennis elbows were r and omised into 3 groups of treatment : ( I ) forearm support b and , ( II ) strengthening exercises and ( III ) both methods . The patients had a st and ardised examination at their first visit , and then after 6 weeks , 3 months and 1 year . At the latest follow-up , there was a significant improvement of the symptoms compared to before treatment ( p<0.0001 ) , considering all patients independently of the methods of treatment . However , no differences in the scores were found between the 3 groups of treatment ( p=0.27 ) , indicating that no beneficial influence was found either for the strengthening exercises or for the forearm support b and . Improvement seems to occur with time , independent of the method of treatment used Background : When using botulinum toxin for the management of lateral epicondylitis , injection at a fixed distance from an anatomic l and mark could result in inadequate paralysis of the intended muscle . We assessed the effectiveness of injection of botulinum toxin using precise anatomic measurement in individual patients . Methods : In this r and omized placebo-controlled trial , 48 patients with chronic refractory lateral epicondylitis were r and omly assigned to receive a single injection of either botulinum toxin ( 60 units ) or placebo ( normal saline ) . The site of injection was chosen as a distance one-third the length of the forearm from the tip of the lateral epicondyle on the course of the posterior interosseus nerve . The primary outcome measure was intensity of pain at rest , measured with the use of a 100-mm visual analogue scale , at baseline and at 4 , 8 and 16 weeks after injection . Results : Compared with the placebo group , the group given botulinum toxin had significant reductions in pain at rest during follow-up ( decrease at 4 weeks 14.1 mm , 95 % confidence interval [ CI ] 5.8–22.3 ; at 8 weeks 11.5 mm , 95 % CI 2.0–21.0 ; at 16 weeks 12.6 mm , 95 % CI 7.7–17.8 ; p = 0.01 ) . As for the secondary outcomes , the intensity of pain during maximum pinch decreased in the botulinum toxin group ; there was no difference in pain during maximum grip or in grip strength between the two groups . All but one of the patients in the intervention group experienced weakness in the extension of the third and fourth fingers at week 4 that resolved by week 16 . No serious adverse events were reported . Interpretation : The use of precise anatomic measurement to guide injection of botulinum toxin significantly reduced pain at rest in patients with chronic refractory lateral epicondylitis . However , the transient extensor lag makes this method inappropriate for patients whose job requires finger extension . ( Clinical Trials.gov trial register no. NCT00497913 . BACKGROUND The Oxford Levels of Evidence are now routinely assigned at many orthopaedic journals . One disadvantage of this approach is that study design s with a higher level of evidence may be given greater weight than the overall quality of the study merits . In other words , there is no guarantee that research is scientifically valid simply because a more sophisticated study design was employed . The aim of this study was to review Level-I and II therapeutic studies on lateral epicondylitis to measure variation in quality among the highest-level study design s. METHODS Fifty-four prospect i ve r and omized therapeutic trials involving patients with lateral epicondylitis were evaluated by two independent review ers according to the Oxford Levels of Evidence , a modification of the Coleman Methodology Score ( a 0 to 100-point scale ) , and the revised CONSORT ( Consoli date d St and ards of Reporting Trials ) score . RESULTS The two review ers were consistent in their use of the Oxford Levels of Evidence ( kappa = 0.73 , p < 0.01 ) , the modified Coleman Methodology Score ( kappa = 0.73 ; p < 0.01 ) , and the CONSORT score ( kappa = 0.53 ; p < 0.01 ) . Both review ers rated the majority of studies as Level II ( 91 % and 94 % ) and as unsatisfactory according to the Coleman Methodology Score ( 87 % and 89 % ) and the CONSORT score ( 62 % and 63 % ) . Areas of deficiency included poor descriptions of recruitment ( > 90 % of the trials ) , power-level calculations ( 73 % ) , r and omization ( 58 % ) , blinding ( 90 % ) , and participant flow ( 50 % ) as well as inadequate follow-up , sample size , and blinding . CONCLUSIONS The use of the gold-st and ard trial design , the prospect i ve r and omized therapeutic study ( Level-I or II evidence ) , does not ensure quality research or reporting . Critical analysis of scientific work is important regardless of the study design . Clinical scientists should be familiar with the CONSORT criteria and adhere to them when reporting clinical trials OBJECTIVE The aim of this study was to investigate if low-level laser therapy ( LLLT ) can modulate acute inflammation and tumor necrosis factor ( TNFalpha ) levels . BACKGROUND DATA Drug therapy with TNFalpha-inhibitors has become st and ard treatment for rheumatoid arthritis , but it is unknown if LLLT can reduce or modulate TNFalpha levels in inflammatory disorders . METHODS Two controlled animal studies were undertaken , with 35 male Wistar rats r and omly divided into five groups each . Rabbit antiserum to ovalbumin was instilled intrabronchially in one of the lobes , followed by the intravenous injection of 10 mg of ovalbumin in 0.5 mL to induce acute lung injury . The first study served to define the time profile of TNFalpha activity for the first 4 h , while the second study compared three different LLLT doses to a control group and a chlorpromazine group at a timepoint where TNFalpha activity was increased . The rats in LLLT groups were irradiated within 5 min at the site of injury by a 650-nm Ga-Al-As laser . RESULTS There was a time-lag before TNFalpha activity increased after BSA injection . TNFalpha levels increased from < or = 6.9 ( 95 % confidence interval [ CI ] , 5.6 - 8.2 ) units/mL in the first 3 h to 62.1 ( 95 % CI , 60.8 - 63.4 ) units/mL ( p < 0.001 ) at 4 h. An LLLT dose of 0.11 Joules administered with a power density of 31.3 mW/cm(2 ) in 42 sec significantly reduced TNFalpha level to 50.2 ( 95 % CI , 49.4 - 51.0 ) , p < 0.01 units/mL versus control . Chlorpromazine reduced TNFalpha level to 45.3 ( 95 % CI , 44.0 - 46.6 ) units/mL , p < 0.001 versus control . CONCLUSION LLLT can reduce TNFalpha expression after acute immunocomplex lung injury in rats , but LLLT dose appears to be critical for reducing TNFalpha release Background : “ Tennis elbow ” is a difficult condition to treat . Ultrasonography ( US ) and colour Doppler ( CD ) guided injections with polidocanol targeting the area with increased blood flow in the extensor origin have shown promising clinical results . Objective : To evaluate and compare effects of US and CD guided intratendinous injections with sclerosing polidocanol and a local anaesthetic ( lidocaine + epinephrine ) , in patients with tennis elbow . Design : Prospect i ve , r and omised , controlled , double-blind , crossover study . Setting : Sports Medicine Unit , Umeå University . Patients : 32 patients ( 36 elbows ) , age range 27 to 66 years , with a long duration of elbow pain diagnosed as tennis elbow , were included in the study . All patients were followed up 3 and 12 months after treatment . Two patients were excluded due to other interventions during the study . Interventions : One US and CD guided injection with the sclerosing agent polidocanol ( group 1 ) or the local anaesthetic lidocaine plus epinephrine ( group 2 ) . At the 3 month follow-up , additional injections with polidocanol were offered to both groups ( crossover for group 2 ) . Main outcome measures : Satisfaction with treatment ( Yes/No ) , elbow pain during activity ( visual analogue scale ) , and maximum voluntary grip strength . Results : There were no significant ( p<0.05 ) differences in the outcome between group 1 and group 2 . In both groups , there was a significantly lower VAS at the 3-month and 12-month follow-ups , and grip strength was significantly higher at the 12-month follow-up . Conclusions : US and CD guided intratendinous injections gave pain relief in patients with tennis elbow . Polidocanol and lidocaine plus epinephrine injections gave similar results Objective : To investigate the effectiveness of sodium diclofenac and sodium salicylate applied by topical iontophoresis and to compare them in the treatment of lateral epicondylitis . Subjects : Forty patients with lateral epicondylitis were r and omized into two groups of 20 patients who were matched for age and sex . Interventions : The patients in one group were treated by iontophoresis of sodium diclofenac and the other group were treated by iontophoresis of sodium salicylate . Then infrared treatment was applied to patients in both groups . Main outcome measures : Pain scores obtained before and after treatment were compared . Results : Pain produced by pressure on the lateral epicondyle , on resisting wrist extension , during function and spontaneous pain at rest significantly decreased in both groups after treatment ( p < 0.001 ) . When pain scores obtained after treatment were compared , greater decrease was observed in the pain produced on resisting wrist extension ( p < 0.01 ) and by pressure on the lateral epicondyle ( p < 0.05 ) in the group treated with sodium diclofenac than in the group treated with sodium salicylate . Conclusions : The results suggest some benefits from the process of iontophoresis and the use of infrared in the treatment of lateral epicondylitis and indicate that iontophoresis of sodium diclofenac is more effective than that of sodium salicylate The objective of this study was to evaluate the effectiveness of eccentric strengthening . Ninety-four subjects ( 50 men ) with chronic lateral epicondylitis were allocated r and omly into three groups : stretching , concentric strengthening with stretching , and eccentric strengthening with stretching . Subjects performed an exercise program for six weeks . All three groups received instruction on icing , stretching , and avoidance of aggravating activities . The strengthening groups received instruction on isolated concentric and eccentric wrist extensor strengthening , respectively . At six weeks , significant gains were made in all three groups as assessed with pain-free grip strength , Patient-rated Forearm Evaluation Question naire , Disabilities of the Arm , Shoulder , and H and question naire , Short Form 36 , and visual analog pain scale . No significant differences in outcome measures were noted among the three groups . Although there were no significant differences in outcome among the groups , eccentric strengthening did not cause subjects to worsen . Further studies are needed to assess the unique effects of a more intense or longer eccentric strengthening program for patients with lateral epicondylitis OBJECTIVE We aim ed to compare the efficacy of two different injection techniques of local corticosteroid and local anesthetic in the management of lateral epicondylitis . METHODS This prospect i ve study followed 80 consecutive patients who were diagnosed with lateral epicondylitis at our hospital outpatient clinic between 2005 and 2006 . Patients were r and omly assigned into two equal groups . Group 1 received a single injection of 1 ml betamethasone and 1 ml prilocaine on the lateral epicondyle at the point of maximum tenderness . Group 2 patients received an injection of the same drug mixture . Following the initial injection , the needle tip was redirected and reinserted down the bone approximately 30 to 40 times without emerging from the skin , creating a hematoma . Patients were evaluated with the Turkish version of the Disabilities of the Arm , Shoulder and H and question naire before injection and at the final follow-up . The unpaired t-test and chi-square tests were used to compare results . RESULTS Sixteen patients in Group 1 and 15 patients in Group 2 were lost during follow-up . The average follow-up period of the remaining 49 patients was 21.6 months . There were no significant differences between the two groups with regard to gender , age , follow-up period , symptom duration , involvement side and number of dominant limbs . The Turkish DASH scores of Group 2 were significantly lower than those of Group 1 ( p=0.017 ) . CONCLUSION Long-term clinical success in the treatment of lateral epicondylitis depends on the injection method . The peppering technique appears to be more effective than the single injection technique in the long-term In a prospect i ve r and omized study of lateral epicondylitis , 120 patients were treated with 2 mL lidocaine ( Group A , n=60 ) or 1 mL lidocaine combined with 1 mL triamcinolone ( Group B , n=60 ) . All injections were done using the peppering technique : after inserting the needle the tender area was peppered with 40 to 50 injections by injecting , withdrawing , redirecting , and reinserting without emerging from the skin . All patients were followed up for 1 year . Fifty-six patients in Group A and 57 patients in Group B had excellent results . There was statistically no difference between the groups . Both groups had excellent results and because the injection of local anesthetics is known to have no long-term effect in the treatment of lateral epicondylitis , the peppering technique seems to be a reliable method of treatment BACKGROUND Radial epicondylitis ( tennis elbow ) is the most frequent type of myotendinosis . Patients can experience substantial loss of function , especially when this condition becomes chronic . A successful therapy has not yet been established . A preliminary study of injections of botulinum toxin A in patients with chronic epicondylitis has shown promising results . METHODS In the present prospect i ve , controlled , double-blinded clinical trial , 130 patients were examined at sixteen study centers . A single injection of botulinum toxin A into the painful origin of the forearm extensor muscles was performed . Follow-up examinations were performed at two , six , twelve , and eighteen weeks . Clinical findings were documented with use of a new clinical pain score and with a visual analogue scale . A global assessment of the result of treatment was also provided by the patient and the attending doctor . Strength of extension of the third finger and the wrist was evaluated with use of the Brunner method , and grip strength ( fist closure strength ) was measured with a vigorimeter . RESULTS The group treated with botulinum toxin A was found to have a significant improvement in the clinical findings , compared with those in the placebo group , as early as the second week after injection ( p = 0.003 ) . Subjective general assessment also showed improvement in that group , compared with the placebo group , at six weeks ( p = 0.001 ) and at the time of the final examination ( at eighteen weeks ) ( p = 0.001 ) . There was a consistent increase in fist closure strength in both the group treated with botulinum toxin A and the control group , but there was no significant difference between groups . As was expected as a side effect , extension of the third finger was observed to be significantly weakened at two weeks but this complication had completely resolved at eighteen weeks . CONCLUSIONS We concluded that local injection of botulinum toxin A is a beneficial treatment for radial epicondylitis ( tennis elbow ) . The treatment can be performed in an outpatient setting and does not impair the patient 's ability to work The efficacy of extracorporeal shock-wave therapy for tennis elbow was investigated using a single fractionated dosage in a r and omised , double-blind study . Outcomes were assessed using the Disabilities of Arm , Shoulder and H and question naire , measurements of grip strength , levels of pain , analgesic usage and the rate of progression to surgery . Informed consent was obtained before patients were r and omised to either the treatment or placebo group . In the final assessment , 74 patients ( 31 men and 43 women ) with a mean age of 43.4 years ( 35 to 71 ) , were included . None of the outcome measures showed a statistically significant difference between the treatment and control groups ( p > 0.05 ) . All patients improved significantly over time , regardless of treatment . Our study showed no evidence that extracorporeal shock-wave therapy for tennis elbow is better than placebo PURPOSE We design ed a prospect i ve , r and omized study to evaluate the effects of iontophoresis delivery of dexamethasone versus corticosteroid injection therapy on patient outcomes . METHODS We r and omized 82 patients to 10 mg dexamethasone via iontophoresis using a self-contained patch with a 24-hour battery ; 10 mg dexamethasone injection ; or 10 mg triamcinolone injection . All patients received the same h and therapy protocol . Primary outcomes tracked were change in grip strength ( flexion vs extension ) , pain , and function scores on a vali date d question naire . The secondary outcome was return-to-work status . Patients were evaluated at baseline , completion of physical therapy , and 6-month follow-up . RESULTS The iontophoresis patients had statistically significant improvement in grip strength at the conclusion of h and therapy compared with baseline . They were also more likely to get back to work without restriction . By 6-month follow-up , all groups had equivalent results for all measured outcomes . CONCLUSIONS Dexamethasone via iontophoresis produced short-term benefits because for this group grip strength and unrestricted return to work were significantly better . This study suggests that this iontophoresis technique for delivery of corticosteroid may be considered a treatment option for patients with lateral epicondylitis . TYPE OF STUDY /LEVEL OF EVIDENCE Therapeutic II Background The authors evaluated the effectiveness of brace-only treatment , physical therapy , and the combination of these for patients with tennis elbow . Methods Patients were r and omized over 3 groups : brace-only treatment , physical therapy , and the combination of these . Main outcome measures were success rate , severity of complaints , pain , disability , and satisfaction . Data were analyzed using both intention-to-treat and per- protocol analyses . Follow-up was 1 year . Results A total of 180 patients were r and omized . Physical therapy was superior to brace only at 6 weeks for pain , disability , and satisfaction . Contrarily , brace-only treatment was superior on ability of daily activities . Combination treatment was superior to brace on severity of complaints , disability , and satisfaction . At 26 weeks and 52 weeks , no significant differences were identified . Conclusion Conflicting results were found . Brace treatment might be useful as initial therapy . Combination therapy has no additional advantage compared to physical therapy but is superior to brace only for the short term The histopathologic features from 11 patients who were treated surgically for lateral epicondylitis were grade d and compared to similar tissue from 12 cadaveric spec imens . All studies were done by a single pathologist who had no knowledge of the origin of the specimen . The surgical specimens were interpreted as abnormal in all 11 specimens , and all 12 of the control specimens were reported as being without histologic abnormality . Vascular proliferation was present in 10 of 11 and focal hyaline degeneration was recorded in all 11 of the surgical specimens . Neither feature was present in any of the control material ( P < 0.001 ) . These data suggest that chronic refractory lateral epicondylitis requiring sur gery is a degenerative rather than inflammatory proc ess . This may account for the lack of response to rest and antiinflammatory medication BACKGROUND AND OBJECTIVE There are conflicting reports regarding the efficacy of low energy laser therapy in treatment of lateral epicondylitis ( LE ) . Contradictory results are considered to be due to different joint treatment protocol s regarding variables such as dose , duration , and frequency . The aim of this study was to investigate the efficacy of gallium-arsenide ( GaAs ) laser therapy , which was performed with the dose regimen recommended by the World Association for Laser Therapy , in relieving pain and improving functional activities in patients with LE . PATIENTS AND METHODS Forty-nine patients ( 50 elbows ) evaluated in our outpatient clinic were included in the study . Elbows were r and omized into two groups : laser ( n = 25 ) and placebo laser ( n = 25 ) . Either laser or placebo laser therapy was applied to patients for 15 sessions ( 5 d per week for 3 weeks ) . Main outcome measures were visual analog scale , tenderness , Disability of the Arm Shoulder and H and ( DASH ) question naire , the Patient-Related Lateral Epicondylitis Evaluation ( PRTEE ) test , pain-free grip strength , and the Nottingham Health Profile ( NHP ) question naire . Evaluations were performed before treatment , at the end of 3 weeks of treatment , and after the 12th week of treatment ended . RESULTS Upon post-treatment evaluation , a significant improvement in all parameters was observed for both groups ( p < 0.05 ) . No significant difference was found when the laser and placebo groups were compared . At the 12 week evaluation , a significant sustained improvement in all parameters was observed . On intergroup evaluation , a significant improvement was observed in favor of the active treatment group regarding pain with resisted extension of the wrist , tenderness with pressure , and for both the total and subgroup scores of the DASH question naire and PRTEE test , as well as for the pain subgroup of the NHP question naire ( p < 0.05 ) . CONCLUSION Although low energy laser therapy had no advantage compared to placebo in patients with LE for the short term , a significant improvement , particularly in functional parameters , was achieved in the long term . Laser , which has relatively no side effects , might be included among long-term treatment options for LE Objective To analyze whether a corticosteroid injection in combination with rehabilitation early in the course of lateral epicondylitis ( LE ) alters the outcome up to 6 months after injection compared with a control injection and rehabilitation . Design R and omized , controlled , double-blind study . Setting Sports medicine center in a tertiary care center . Participants ubjects with a diagnosis of LE whose symptoms had been present less than 4 weeks were included . Subjects were recruited by word of mouth and through advertising . The 39 subjects who were recruited were 18 to 65 years old . Interventions 19 subjects were r and omized to receive rehabilitation and a sham injection , and 20 were r and omized to receive rehabilitation and a corticosteroid injection . At 4 and 8 weeks , they were reevaluated and their treatment programs were modified , if indicated . Main Outcome Measures Outcome measurements were performed at baseline , 4 weeks , 8 weeks , and 6 months , and included a functional pain question naire and a visual analogue pain scale . Painless grip strength on the affected side and maximal grip strength bilaterally were measured at baseline , 4 weeks , and 8 weeks . Results There were no significant differences in outcome between the two groups with the exception of an improvement in the visual analogue pain scale in the corticosteroid group from 8 weeks to 6 months . Outcome measurements in both groups improved significantly over time ; more than 80 % of subjects reported improvements from baseline to 6 months for all scales . Conclusion A corticosteroid injection does not provide a clinical ly significant improvement in the outcome of LE , and rehabilitation should be the first line of treatment in patients with a short duration of symptoms Background Growth factor technologies are increasingly used to enhance healing in musculoskeletal injuries , particularly in sports medicine . Two such products ; platelet-rich plasma ( PRP ) and autologous blood , have a growing body of supporting evidence . No previous trial has directly compared the efficacy of these two methods . Hypothesis Growth factor administration improves tissue regeneration in patients who have failed to respond to conservative therapy . Study design A prospect i ve , double-blind , r and omised trial . Methods Elbow tendinopathy patients who had failed conservative physical therapy were divided into two patient groups : PRP injection ( N=80 ) and autologous blood injection ( ABI ) ( N=70 ) . Each patient received two injections at 0 and 1 month . Patient-related tennis elbow evaluation ( PRTEE ) was recorded by a blinded investigator at 0 , 1 , 3 and 6 months . The main outcome measure was PRTEE , a vali date d composite outcome for pain , activities of daily living and physical function , utilising a 0–100 scale . Results At 6 months the authors observed a 66 % success rate in the PRP group versus 72 % in the ABI group , p = NS . There was a higher rate of conversion to surgery in the ABI group ( 20 % ) versus the PRP group ( 10 % ) . Conclusion In patients who are resistant to first-line physical therapy such as eccentric loading , ABI or PRP injections are useful second-line therapies to improve clinical outcomes . In this study , up to seven out of 10 additional patients in this difficult to treat cohort benefit from a surgery-sparing intervention Thirty-six patients with lateral epicondylitis of the elbow ( 19 women , 17 men , median age 48 yrs ) were treated either with active laser or placebo , 18 patients in each group . The active laser was a GA-AL-AS 30 mW/830 nm low power laser ( LPL ) . The study design was double blind and r and omized . The treatment session consisted of eight treatments , two per week . Patients were irradiated on tender points on the lateral epicondyle and in the forearm extensors . Output power was 3,6 J/point . A follow up was performed by telephone , 10 weeks after the last treatment . No difference between laser and placebo was found on lateral elbow pain ( Mann Whitney test , 95 % confidence limits ) . We conclude that low power laser offers no advantage over placebo in the treatment of musculoskeletal pain as lateral epicondylitis . Further studies with low power laser treatment of musculoskeletal pain seem useless We report a controlled , prospect i ve study to investigate the effect of treatment by low-energy extracorporeal shock waves on pain in tennis elbow . We assigned at r and om 100 patients who had had symptoms for more than 12 months to two groups to receive low-energy shock-wave therapy . Group I received a total of 3000 impulses of 0.08 mJ/mm2 and group II , the control group , 30 impulses . The patients were review ed after 3 , 6 and 24 weeks . There was significant alleviation of pain and improvement of function after treatment in group I in which there was a good or excellent outcome in 48 % and an acceptable result in 42 % at the final review , compared with 6 % and 24 % , respectively , in group II Background : On the basis of observational trials , numerous investigators have recommended extracorporeal shock wave therapy as an alternative treatment for chronic lateral epicondylitis of the elbow . However , there has been no evidence of its efficacy from well- design ed r and omized clinical trials . The objective of this study was to find out whether extracorporeal shock wave therapy in combination with local anesthesia was superior to placebo therapy in combination with local anesthesia . Methods : A r and omized multicenter trial with a parallel-group design was conducted . Following administration of local anesthesia , either extracorporeal shock wave therapy with three treatments of 2000 pulses each and a positive energy flux density ( ED+ ) of 0.07 to 0.09 mJ/mm 2 or placebo therapy was applied on an outpatient basis . Treatment allocation was blinded for patients and for observers . The primary end point was based on the rate of success , as determined with the Roles and Maudsley score and whether additional treatment was required , twelve weeks after the intervention . Crossover was possible after assessment of the primary end point . Secondary end points were the Roles and Maudsley score , subjective pain rating , and grip strength after six and twelve weeks and after twelve months . The planned number of 272 patients was included in the study . Results : The primary end point could be assessed for 90.8 % of the patients . The success rate was 25.8 % in the group treated with extracorporeal shock wave therapy and 25.4 % in the placebo group , a difference of 0.4 % with a 95 % confidence interval of -10.5 % to 11.3 % . Similarly , there was no relevant difference between groups with regard to the secondary end points . Improvement was observed in two-thirds of the patients from both groups twelve months after the intervention . Few side effects were reported . Conclusions : Extracorporeal shock wave therapy as applied in the present study was ineffective in the treatment of lateral epicondylitis . The previously reported success of this therapy appears to be attributable to inappropriate study design s. Different application protocol s might improve clinical outcome . We recommend that extracorporeal shock wave therapy be applied only in high- quality clinical trials until it is proved to be effective The effect of low level laser ( GaAs ) on lateral epicondylitis was investigated in a double-blind , r and omized , controlled study . Thirty patients were assigned equally to a laser ( n = 15 ) or a placebo laser ( n = 15 ) group . All patients received eight treatments and were evaluated subjectively and objective ly before , at the end of , and four weeks after treatment . Patients also completed a follow-up question naire on an average of five to six months after treatment . A significant improvement in the laser compared to the placebo group was found on visual analog scale ( p = 0.02 ) and grip strength ( p = 0.03 ) tests four weeks after treatment . In this study low level laser therapy was shown to have an effect over placebo ; however , as a sole treatment for lateral epicondylitis it is of limited value . Further studies are needed to evaluate the reliability of our findings and to compare laser to other established treatment methods The relative merits of a watch and wait policy , physiotherapy alone , steroid injection therapy alone , and physiotherapy and steroid injection therapy combined , for the treatment of tennis elbow , were assessed using a prospect i ve r and omised controlled trial ( RCT ) of factorial design . Although RCTs comparing different treatment strategies for tennis elbow have previously been published , to our knowledge none of the previous studies have combined the modalities of physiotherapy and steroid injection as one of the treatment groups , as we have done in this study . Patients who received steroid injection were statistically significantly better for all outcome measures at follow up . No statistically significant effect of physiotherapy nor interaction between physiotherapy and injection was found . On the basis of the results of this study , the authors advocate steroid injection alone as the first line of treatment for patients presenting with tennis elbow dem and ing a quick return to daily activities The purpose s of this study were to compare the pain alleviating effects of laser treatment and placebo in tennis elbow . Also , the effects of laser radiation on the radial sensory nerve conduction , and the temperature changes in the tissue surrounding the treated radial nerve were studied . The results show that laser treatment is not significantly better than placebo in treating tennis elbow . Furthermore , no significant change was noted in the evoked sensory potential as well as subcutaneous temperatures in either experimental or control groups as a result of the applications of the laser radiation treatment Objective : To describe the outcomes of a cohort of individuals involved in a r and omized control trial of extracorporeal shockwave therapy ( ESWT ) in the treatment of lateral epicondylitis ( LE ) not previously treated . Design : Prospect i ve cohort . Setting : General population . Patients : Sixty subjects ( 23 female , 37 male ) who participated in a double-blind r and omized control trial on the effectiveness of ESWT in the treatment of LE . All subjects had previously not received therapy for their LE . Intervention : At the 8-week follow-up of a r and omized control trial comparing ESWT with a stretching protocol for treatment of LE , all subjects were unblinded to their treatment allocation , and subjects initially allocated to sham therapy were offered active therapy . Main Outcome Measures : Overall elbow pain ( 10-cm visual analogue scale [ VAS ] ) and maximum pain-free grip strength were evaluated at 0 , 4 , and 8 weeks and 3 , 6 , and 9 to 12 months postinitiation of therapy . Time to pain-free status ( less than 1 cm on the VAS ) was calculated from time of onset of symptoms , time of inclusion into the trial , and time from initiation of active therapy . Main Results : A statistically significant difference in time to pain-free status was not detected between groups . Duration of symptoms was identified to be an effect modifier of early response to therapy ( at least 50 % improvement on the VAS at 8-week postinitiation of therapy ) . A higher proportion of subjects treated within 16 weeks of onset of LE symptoms showed a response to ESWT than subjects treated after 16 weeks of onset of their LE symptoms . Conclusions : The use of ESWT with a stretching program is not supported by this study , with the possible exception of the possible interaction effect of time of ESWT initiation from the time of onset of symptoms , which requires further investigation OBJECTIVE To evaluate the efficacy of an oral nonsteroidal anti-inflammatory drug in the treatment of lateral epicondylitis . DESIGN Multicenter double-blind r and omized controlled trial in which the following hypothesis was tested : whether diclofenac sodium provided a 20 % or greater improvement over rest and cast immobilization in the response rate to treatment of lateral epicondylitis beyond and over rest in an experimental group compared with a control group after 4 weeks of treatment . SETTING Recruitment from urban general practice s and referrals to 4 university hospitals . SUBJECTS AND METHODS During a 1-year period , 206 subjects aged 18 to 60 years with lateral epicondylitis were recruited from the clientele treated by family physicians . Thirty subjects refused to participate and 47 presented with exclusion criteria , leaving 129 subjects who entered the study . One subject withdrew after 21 days . INTERVENTIONS The experimental group was treated with a daily dose of diclofenac sodium ( 150 mg ) for 28 days , while the control group received a placebo during the same period . In addition , both groups were immobilized in a cast for 14 days and were told not to perform repetitive movements of the involved limb for 21 days . MAIN OUTCOME MEASURES Measuring instruments consisted of grip strength measurements with a squeeze dynamometer , a visual analog pain scale , a visual analog function scale , and an 8-item pain-free function index . RESULTS A statistically and clinical ly significant reduction of pain was associated with treatment with diclofenac , but no clinical ly significant difference in grip strength or functional improvement could be detected between the 2 groups . Secondary effects ( diarrhea and abdominal pain ) were significantly more frequent in the diclofenac-treated group . CONCLUSION Taking into account the limited improvement noted over rest and cast immobilization and the number of associated adverse events , it is difficult to recommend the use of diclofenac in the treatment of lateral epicondylitis at the dosage used in this study OBJECTIVE To assess the effectiveness of low intensity laser therapy in the treatment of lateral epicondylitis . DESIGN A double-masked , placebo-controlled , r and omized clinical trial . SETTING A physical medicine and rehabilitation clinic . PARTICIPANTS Fifty-two ambulatory men and women ( age range , 18 - 70 yr ) with symptomatic lateral epicondylitis of more than 30 days in duration and a normal neurologic examination . INTERVENTION Subjects were bloc r and omized into 2 groups with a computer-generated schedule . All underwent irradiation for 60 seconds at 7 points along the symptomatic forearm 3 times weekly for 4 weeks by a masked therapist . The sole difference between the groups was that the probe of a 1.06-microm continuous wave laser emitted 204 mW/cm2 ( 12.24 J/cm2 ) for the treated subjects and was inactive for the control subjects . Subjects were assessed at the beginning , midpoint ( session 6 ) , and end ( session 12 ) of treatment , as well as at follow-up 28 to 35 days after their last treatment . MAIN OUTCOME MEASURES Pain in last 24 hours , tenderness to palpation , and patient 's perception of change ( benefit ) . RESULTS The treated and untreated groups were well matched demographically . Masking was maintained for subjects and therapists ; however , the groups did not vary to a statistically significant extent in terms of the main outcome measures either during treatment or at follow-up . Secondary outcome variables , such as grasp and pinch strength , medication use , and pain with grasp and pinch , also failed to statistically differ significantly between the groups . No significant treatment side effects were noted . CONCLUSION Treatment with low intensity 1.06-microm laser irradiation within the parameters of this study was a safe but ineffective treatment of lateral epicondylitis . Further research seems warranted in this controversial area PURPOSE We tested the hypothesis that there is no difference in disability , pain , and grip strength 1 and 6 months after corticosteroid and lidocaine injection compared with lidocaine injection alone ( placebo ) . METHODS Sixty-four patients were r and omly assigned to dexamethasone ( n = 31 ) or placebo ( n = 33 ) injection . At enrollment , disability ( Disabilities of the Arm , Shoulder , and H and [ DASH ] question naire ) , pain on a visual analog scale , grip strength , depression ( the Center for Epidemiologic Studies Depression Scale ; CESD ) , and ineffective coping skills ( the Pain Catastrophizing Scale ; PCS ) were comparable between treatment groups . At 1 and 6 months , DASH , pain , and grip strength measures were repeated . Univariate and multivariate analyses were used to determine predictors of disability . Analysis was by intention to treat . RESULTS One month after injection , DASH scores averaged 24 versus 27 points ( dexamethasone vs placebo ) , pain 3.7 versus 4.3 cm , and grip strength 83 % versus 87 % . At 6 months , DASH scores averaged 18 versus 13 points , pain 2.4 versus 1.7 cm , and grip strength 98 % versus 97 % . CESD and PCS scores correlated with disability as measured by the DASH question naire . The best multivariate models included CESD at 1 month and PCS scores at 6 months and explained the majority of variability in DASH scores . CONCLUSIONS Corticosteroid injection did not affect the apparently self-limited course of lateral elbow pain . In secondary analyses in a subset of patients , perceived disability associated with lateral elbow pain correlated with depression and ineffective coping skills . TYPE OF STUDY /LEVEL OF EVIDENCE Therapeutic OBJECTIVE The aims of this double-blind , r and omized , placebo-controlled trial were to determine whether ultrasound-guided extracorporeal shock wave therapy ( ESWT ) reduced pain and improved function in patients with lateral epicondylitis ( tennis elbow ) in the short term and intermediate term . METHODS Sixty-eight patients from community-based referring doctors were r and omized to receive 3 ESWT treatments or 3 treatments at a subtherapeutic dose given at weekly intervals . Seven outcome measures relating to pain and function were collected at followup evaluations at 6 weeks , 3 months , and 6 months after completion of the treatment . The mean changes in outcome variables from baseline to 6 weeks , 3 months , and 6 months were compared for the 2 groups . RESULTS The groups did not differ on demographic or clinical characteristics at baseline and there were significant improvements in almost all outcome measures for both groups over the 6-month followup period , but there were no differences between the groups even after adjusting for duration of symptoms . CONCLUSION Our study found little evidence to support the use of ESWT for the treatment of lateral epicondylitis and is in keeping with recent systematic review s of ESWT for lateral epicondylitis that have drawn similar conclusions UNLABELLED Extracorporeal shock wave therapy ( ESWT ) is an increasingly popular therapeutic approach to the treatment of a number of soft tissue complaints . Whilst benefit has been demonstrated in calcific tendinitis , evidence is lacking for benefit in the management of non-calcific rotator cuff disorders . AIMS To perform a double-blind placebo controlled trial of moderate dose ESWT in chronic lateral epicondylitis . METHODS Adults with lateral epicondylitis were r and omised to receive either active treatment ( 1500 pulses ESWT at 0.12 mJ/ mm2 ) or sham therapy , monthly for three months . All were assessed before each treatment and one month after completion of therapy . Outcome measures consisted of visual analogue scores for pain in the day and at night . RESULTS Seventy-five subjects participated and there were no significant differences between the two groups at baseline . The mean duration of symptoms was 15.9 and 12 months in the ESWT and sham groups , respectively . Both groups showed significant improvements from two months . No significant difference existed between the groups with respect to the degrees of change in pain scores over the study period . In the ESWT group the mean ( SD , range ) pain score was 73.4 ( 14.5 , 38 - 99 ) at baseline and 47.9 ( 31.4 , 3 - 100 ) at three months . In the sham group the mean ( SD , range ) pain score was 67.2 ( 21.7 , 12 - 100 ) at baseline and 51.5 ( 32.5 , 3 - 100 ) at three months . At three months , 50 % improvement from baseline was noted in 35 % of the ESWT group and 34 % of the sham group with respect to pain . CONCLUSIONS There appears to be a significant placebo effect of moderate dose ESWT in subjects with lateral epicondylitis but there is no evidence of added benefit of treatment when compared to sham therapy IMPORTANCE Corticosteroid injection and physiotherapy , common treatments for lateral epicondylalgia , are frequently combined in clinical practice . However , evidence on their combined efficacy is lacking . OBJECTIVE To investigate the effectiveness of corticosteroid injection , multimodal physiotherapy , or both in patients with unilateral lateral epicondylalgia . DESIGN , SETTING , AND PATIENTS A 2 × 2 factorial , r and omized , injection-blinded , placebo-controlled trial was conducted at a single university research center and 16 primary care setting s in Brisbane , Australia . A total of 165 patients aged 18 years or older with unilateral lateral epicondylalgia of longer than 6 weeks ' duration were enrolled between July 2008 and May 2010 ; 1-year follow-up was completed in May 2011 . INTERVENTIONS Corticosteroid injection ( n = 43 ) , placebo injection ( n = 41 ) , corticosteroid injection plus physiotherapy ( n = 40 ) , or placebo injection plus physiotherapy ( n = 41 ) . MAIN OUTCOME MEASURES The 2 primary outcomes were 1-year global rating of change scores for complete recovery or much improvement and 1-year recurrence ( defined as complete recovery or much improvement at 4 or 8 weeks , but not later ) analyzed on an intention-to-treat basis ( P < .01 ) . Secondary outcomes included complete recovery or much improvement at 4 and 26 weeks . RESULTS Corticosteroid injection result ed in lower complete recovery or much improvement at 1 year vs placebo injection ( 83 % vs 96 % , respectively ; relative risk [ RR ] , 0.86 [ 99 % CI , 0.75 - 0.99 ] ; P = .01 ) and greater 1-year recurrence ( 54 % vs 12 % ; RR , 0.23 [ 99 % CI , 0.10 - 0.51 ] ; P < .001 ) . The physiotherapy and no physiotherapy groups did not differ on 1-year ratings of complete recovery or much improvement ( 91 % vs 88 % , respectively ; RR , 1.04 [ 99 % CI , 0.90 - 1.19 ] ; P = .56 ) or recurrence ( 29 % vs 38 % ; RR , 1.31 [ 99 % CI , 0.73 - 2.35 ] ; P = .25 ) . Similar patterns were found at 26 weeks , with lower complete recovery or much improvement after corticosteroid injection vs placebo injection ( 55 % vs 85 % , respectively ; RR , 0.79 [ 99 % CI , 0.62 - 0.99 ] ; P < .001 ) and no difference between the physiotherapy and no physiotherapy groups ( 71 % vs 69 % , respectively ; RR , 1.22 [ 99 % CI , 0.97 - 1.53 ] ; P = .84 ) . At 4 weeks , there was a significant interaction between corticosteroid injection and physiotherapy ( P = .01 ) , whereby patients receiving the placebo injection plus physiotherapy had greater complete recovery or much improvement vs no physiotherapy ( 39 % vs 10 % , respectively ; RR , 4.00 [ 99 % CI , 1.07 - 15.00 ] ; P = .004 ) . However , there was no difference between patients receiving the corticosteroid injection plus physiotherapy vs corticosteroid alone ( 68 % vs 71 % , respectively ; RR , 0.95 [ 99 % CI , 0.65 - 1.38 ] ; P = .57 ) . CONCLUSION AND RELEVANCE Among patients with chronic unilateral lateral epicondylalgia , the use of corticosteroid injection vs placebo injection result ed in worse clinical outcomes after 1 year , and physiotherapy did not result in any significant differences . TRIAL REGISTRATION anzctr.org Identifier : ACTRN12609000051246 |
1,212 | 24,974,369 | The preponderance of evidence suggests that there is high collinearity between PSA and PSAV and therefore the calculation of PSAV adds little to the measurement of PSA level .
PSAV calculation has been advocated by many investigators as a strategy to improve the screening and clinical management of patients with CaP. However , when PSAV definitions are rigorously applied , its calculation does not significantly enhance the clinical performance of PSA alone | BACKGROUND The value of prostate-specific antigen ( PSA ) for screening and management of prostate cancer ( CaP ) continues to engender much controversy in the medical and lay literature . | UNLABELLED PSA-driven screening has been applied to a large part of the male population in many countries . An elevated PSA in secondary screens may indicate benign enlargement of the prostate rather than prostate cancer . In such cases the yearly rate of increase of PSA ( PSA velocity [ PSAV ] ) may improve the test characteristics of PSA . MATERIAL S AND METHODS Data from the European R and omized Study of Screening for Prostate Cancer Rotterdam are used to study the issue . Relative sensitivity , relative specificity , and positive predictive value ( PPV ) are calculated . Logistic regression analysis is used to compare odds ratios for positive biopsies . The relationship between PSAV and parameters of tumour aggressiveness is investigated . RESULTS Five hundred eighty-eight consecutive participants were identified who presented at their first screening with PSA values < 4.0 and who progressed to PSA values > 4.0 ng/ml four years later . None were biopsied in round one , all were biopsied in round two . Relative sensitivity and specificity depend strongly on PSAV cut-offs of 0.25 - 1.0 ng/ml/yr . The use of PSAV cut-offs does not improve the PPV of the PSA cut-off of 4.0 ng/ml , nor do any of the PSAV cut-offs improve the odds ratio for identifying prostate cancer with respect to the cut-off value of 4.0 ng/ml . The rate of aggressive cancers seems to increase with increasing PSAV . CONCLUSIONS PSAV does not improve the detection characteristics of a PSA cut-off of 4.0 ng/ml in secondary screening after four years BACKGROUND Several trials evaluating the effect of prostate-specific antigen ( PSA ) testing on prostate-cancer mortality have shown conflicting results . We up date d prostate-cancer mortality in the European R and omized Study of Screening for Prostate Cancer with 2 additional years of follow-up . METHODS The study involved 182,160 men between the ages of 50 and 74 years at entry , with a predefined core age group of 162,388 men 55 to 69 years of age . The trial was conducted in eight European countries . Men who were r and omly assigned to the screening group were offered PSA-based screening , whereas those in the control group were not offered such screening . The primary outcome was mortality from prostate cancer . RESULTS After a median follow-up of 11 years in the core age group , the relative reduction in the risk of death from prostate cancer in the screening group was 21 % ( rate ratio , 0.79 ; 95 % confidence interval [ CI ] , 0.68 to 0.91 ; P=0.001 ) , and 29 % after adjustment for noncompliance . The absolute reduction in mortality in the screening group was 0.10 deaths per 1000 person-years or 1.07 deaths per 1000 men who underwent r and omization . The rate ratio for death from prostate cancer during follow-up years 10 and 11 was 0.62 ( 95 % CI , 0.45 to 0.85 ; P=0.003 ) . To prevent one death from prostate cancer at 11 years of follow-up , 1055 men would need to be invited for screening and 37 cancers would need to be detected . There was no significant between-group difference in all-cause mortality . CONCLUSIONS Analyses after 2 additional years of follow-up consoli date d our previous finding that PSA-based screening significantly reduced mortality from prostate cancer but did not affect all-cause mortality . ( Current Controlled Trials number , IS RCT N49127736 . ) BACKGROUND The optimal upper limit of the normal range for prostate-specific antigen ( PSA ) is unknown . We investigated the prevalence of prostate cancer among men in the Prostate Cancer Prevention Trial who had a PSA level of 4.0 ng per milliliter or less . METHODS Of 18,882 men enrolled in the prevention trial , 9459 were r and omly assigned to receive placebo and had an annual measurement of PSA and a digital rectal examination . Among these 9459 men , 2950 men never had a PSA level of more than 4.0 ng per milliliter or an abnormal digital rectal examination , had a final PSA determination , and underwent a prostate biopsy after being in the study for seven years . RESULTS Among the 2950 men ( age range , 62 to 91 years ) , prostate cancer was diagnosed in 449 ( 15.2 percent ) ; 67 of these 449 cancers ( 14.9 percent ) had a Gleason score of 7 or higher . The prevalence of prostate cancer was 6.6 percent among men with a PSA level of up to 0.5 ng per milliliter , 10.1 percent among those with values of 0.6 to 1.0 ng per milliliter , 17.0 percent among those with values of 1.1 to 2.0 ng per milliliter , 23.9 percent among those with values of 2.1 to 3.0 ng per milliliter , and 26.9 percent among those with values of 3.1 to 4.0 ng per milliliter . The prevalence of high- grade cancers increased from 12.5 percent of cancers associated with a PSA level of 0.5 ng per milliliter or less to 25.0 percent of cancers associated with a PSA level of 3.1 to 4.0 ng per milliliter . CONCLUSIONS Biopsy-detected prostate cancer , including high- grade cancers , is not rare among men with PSA levels of 4.0 ng per milliliter or less -- levels generally thought to be in the normal range PURPOSE Prostate specific antigen is a glycoprotein found almost exclusively in normal and neoplastic prostate cells . Prostate specific antigen doubling time , or the change in prostate specific antigen over time , has emerged as a useful predictive marker for assessing disease outcome in patients with prostate cancer . It is important to agree on definitions and values for the calculation of prostate specific antigen doubling time , and to develop a common approach to outcome analysis and reporting . MATERIAL S AND METHODS In September 2006 a conference was held at the National Cancer Institute in Bethesda , Maryl and to define these parameters and develop guidelines for their use . RESULTS The Prostate Specific Antigen Working Group defined criteria regarding prostate specific antigen doubling time including the calculation of prostate specific antigen doubling time , evidence to support prostate specific antigen doubling time as a predictive factor in the setting of biochemical recurrence and the use of prostate specific antigen doubling time as a stratification factor in clinical trials . CONCLUSIONS We propose that investigators calculate prostate specific antigen doubling time before enrolling patients in clinical studies and calculate it as an additional measurement of therapeutic activity . We believe we have developed practical guidelines for the calculation of prostate specific antigen doubling time and its use as a measurement of prognosis and outcome . Furthermore , the use of common st and ards for prostate specific antigen doubling time in clinical trials is important as we determine which treatments should progress to r and omized trials in which " hard " end points such as survival will be used Prostate-specific antigen velocity ( PSAV ) is one of the oldest concepts in PSA screening , yet today it is one of the most controversial . Publication of a wide range of studies with different design s , study population s , and results has fueled uncertainty about the best way to use PSAV and confused the issue of its utility in the early detection setting . Studies of disease prognosis suggest that PSAV is strongly associated with lethal cancers . However , prospect i ve screening trials find that PSAV is at best a weak predictor of high-risk disease . In this commentary , we synthesize and reconcile the evidence about the value of PSAV in the early detection setting . We review recent studies of PSAV and determine a set of statistical considerations that we believe to be critical in study evaluation and interpretation . We explain why the association between PSAV and disease-specific survival does not necessarily imply that PSAV will be a useful screening tool . In addition , we argue that the st and ard concept of PSAV -- the absolute change in PSA per year -- confuses disease aggressiveness with the interval from disease onset to detection . We therefore recommend that other methods be explored to incorporate information about PSA kinetics that could ultimately improve-- and even transform -- how we detect and treat prostate cancer BACKGROUND Screening for prostate cancer advances the time of diagnosis ( lead time ) and detects cancers that would not have been diagnosed in the absence of screening ( overdetection ) . Both consequences have considerable impact on the net benefits of screening . METHODS We developed simulation models based on results of the Rotterdam section of the European R and omized Study of Screening for Prostate Cancer ( ERSPC ) , which enrolled 42,376 men and in which 1498 cases of prostate cancer were identified , and on baseline prostate cancer incidence and stage distribution data . The models were used to predict mean lead times , overdetection rates , and ranges ( corresponding to approximate 95 % confidence intervals ) associated with different screening programs . RESULTS Mean lead times and rates of overdetection depended on a man 's age at screening . For a single screening test at age 55 , the estimated mean lead time was 12.3 years ( range = 11.6 - 14.1 years ) and the overdetection rate was 27 % ( range = 24%-37 % ) ; at age 75 , the estimates were 6.0 years ( range = 5.8 - 6.3 years ) and 56 % ( range = 53%-61 % ) , respectively . For a screening program with a 4-year screening interval from age 55 to 67 , the estimated mean lead time was 11.2 years ( range = 10.8 - 12.1 years ) , and the overdetection rate was 48 % ( range = 44%-55 % ) . This screening program raised the lifetime risk of a prostate cancer diagnosis from 6.4 % to 10.6 % , a relative increase of 65 % ( range = 56%-87 % ) . In annual screening from age 55 to 67 , the estimated overdetection rate was 50 % ( range = 46%-57 % ) and the lifetime prostate cancer risk was increased by 80 % ( range = 69%-116 % ) . Extending annual or quadrennial screening to the age of 75 would result in at least two cases of overdetection for every clinical ly relevant cancer detected . CONCLUSIONS These model-based lead-time estimates support a prostate cancer screening interval of more than 1 year BACKGROUND The prostate component of the Prostate , Lung , Colorectal , and Ovarian ( PLCO ) Cancer Screening Trial was undertaken to determine whether there is a reduction in prostate cancer mortality from screening using serum prostate-specific antigen ( PSA ) testing and digital rectal examination ( DRE ) . Mortality after 7 - 10 years of follow-up has been reported previously . We report extended follow-up to 13 years after the trial . METHODS A total of 76 685 men , aged 55 - 74 years , were enrolled at 10 screening centers between November 1993 and July 2001 and r and omly assigned to the intervention ( organized screening of annual PSA testing for 6 years and annual DRE for 4 years ; 38 340 men ) and control ( usual care , which sometimes included opportunistic screening ; 38 345 men ) arms . Screening was completed in October 2006 . All incident prostate cancers and deaths from prostate cancer through 13 years of follow-up or through December 31 , 2009 , were ascertained . Relative risks ( RRs ) were estimated as the ratio of observed rates in the intervention and control arms , and 95 % confidence intervals ( CIs ) were calculated assuming a Poisson distribution for the number of events . Poisson regression modeling was used to examine the interactions with respect to prostate cancer mortality between trial arm and age , comorbidity status , and pretrial PSA testing . All statistical tests were two-sided . RESULTS Approximately 92 % of the study participants were followed to 10 years and 57 % to 13 years . At 13 years , 4250 participants had been diagnosed with prostate cancer in the intervention arm compared with 3815 in the control arm . Cumulative incidence rates for prostate cancer in the intervention and control arms were 108.4 and 97.1 per 10 000 person-years , respectively , result ing in a relative increase of 12 % in the intervention arm ( RR = 1.12 , 95 % CI = 1.07 to 1.17 ) . After 13 years of follow-up , the cumulative mortality rates from prostate cancer in the intervention and control arms were 3.7 and 3.4 deaths per 10 000 person-years , respectively , result ing in a non-statistically significant difference between the two arms ( RR = 1.09 , 95 % CI = 0.87 to 1.36 ) . No statistically significant interactions with respect to prostate cancer mortality were observed between trial arm and age ( P(interaction ) = .81 ) , pretrial PSA testing ( P(interaction ) = .52 ) , and comorbidity ( P(interaction ) = .68 ) . CONCLUSIONS After 13 years of follow-up , there was no evidence of a mortality benefit for organized annual screening in the PLCO trial compared with opportunistic screening , which forms part of usual care , and there was no apparent interaction with age , baseline comorbidity , or pretrial PSA testing PURPOSE Preoperative prostate-specific antigen ( PSA ) velocity ( PSAV ) , or the rate of PSA rise before diagnosis , predicts for risk of cancer death after radical prostatectomy ( RP ) . We evaluated the relative merit of established preoperative factors , including biopsy indices and preoperative PSAV , for their impact on relapse after RP . PATIENTS AND METHODS The outcomes of 202 men who underwent RP were review ed . Biopsies were characterized for grade , percentage positive cores , and total linear tumor length . Surgical specimens were characterized for cancer volume , relative percentage by grade , extracapsular extension , and margin status . Univariate and multivariate analyses were performed with respect to relapse-free survival after RP . RESULTS Thirty-one patients relapsed after RP ( defined as PSA > or = 0.2 ng/mL ) , with a median time to failure of 16 months . Median follow-up was 48 months . Kaplan-Meier relapse-free survival at 5 years was 89 % , compared with 73 % for PSAV < or = 2 v > 2 ng/mL/year ( P = .003 ) . On multivariate analysis , only the biopsy Gleason sum ( P < .008 ; relative risk , > 4.8 ) and the preoperative PSAV ( P < .04 ; relative risk , 3.0 to 4.7 ) remained significant . Patients with a PSAV of > 2 ng/mL/year were more likely to be pT3 ( P = .007 ) , have positive margins ( P = .01 ) , have tumors > 1 mL ( P = .05 ) , and possess > 10 % grade 4/5 tumors ( P = .04 ) . CONCLUSION The preoperative PSAV is a significant independent clinical factor predicting for relapse after RP and also predicts for larger , more aggressive , and more locally advanced tumors . Its inclusion will be useful in risk stratification , evaluation for alternatives to surgery , and patient selection for neoadjuvant or adjuvant therapies as part of r and omized clinical trials OBJECTIVE To evaluate longitudinal changes in prostate-specific antigen ( PSA ) levels in men with and without prostate disease . DESIGN Case-control study of men with and without prostate disease who were participants in a prospect i ve aging study . SETTING Gerontology Research Center of the National Institute on Aging ; the Baltimore ( Md ) Longitudinal Study of Aging . PATIENTS Sixteen men with no prostate disease ( control group ) , 20 men with a histologic diagnosis of benign prostatic hyperplasia ( BPH ) , and 18 men with a histologic diagnosis of prostate cancer . OUTCOME MEASURES Multiple PSA and and rogen determinations on serum sample s obtained from 7 to 25 years prior to histologic diagnosis or exclusion of prostate disease . RESULTS Changes in and rogen levels with age did not differ between groups . Control subjects did not show a significant change in PSA levels with age . There was a significant difference in the age-adjusted rate of change in PSA levels between groups ( prostate cancer greater than BPH greater than control ; P less than .01 ) . At 5 years before diagnosis when PSA levels did not differ between subjects with BPH and prostate cancer , rate of change in PSA levels ( 0.75 micrograms/L per year ) was significantly greater in subjects with prostate cancer compared with control subjects and subjects with BPH . Also , rate of change in PSA levels distinguished subjects with prostate cancer from subjects with BPH and control subjects with a specificity of 90 % and 100 % , respectively . CONCLUSIONS The most significant factor affecting serum PSA levels with age is the development of prostate disease . Rate of change in PSA levels may be a sensitive and specific early clinical marker for the development of prostate cancer PURPOSE Controversy exists as to whether current pretreatment prostate-specific antigen ( PSA ) dynamics enhance outcome prediction in patients undergoing treatment for prostate cancer . We assessed whether pretreatment PSA velocity ( PSAV ) or doubling time ( PSADT ) predicted outcome in men undergoing radical prostatectomy and whether any definition enhanced accuracy of an outcome prediction model . PATIENTS AND METHODS The cohort included 2,938 patients with two or more PSA values before radical prostatectomy . Biochemical recurrence ( BCR ) occurred in 384 patients , and metastases occurred in 63 patients . Median follow-up for patients without BCR was 2.1 years . We used univariate Cox proportional hazards regression to evaluate associations between published definitions of PSADT and PSAV with BCR and metastasis . Predictive accuracy was assessed using the concordance index . RESULTS On univariate analysis , two of 12 PSADT and four of 10 PSAV definitions were univariately associated with both BCR and metastasis ( P < .05 ) . One PSADT and one PSAV definition had a higher predictive accuracy for BCR over PSA alone , and four PSAV definitions improved prediction of metastasis . However , the improvements in predictive accuracy were small , associated with wide CIs , and markedly reduced if additional predictors of stage and grade were included alongside PSA . Modeling with r and om variables suggests that similar results would be expected by chance . CONCLUSION We found no clear evidence that any definition of PSA dynamics substantially enhances the predictive accuracy of a single pretreatment PSA alone PURPOSE Studies have shown that finasteride decreases prostate specific antigen ( PSA ) by approximately 50 % during the first 12 months of use . We estimated the long-term effects of finasteride on PSA in men with and without a prostate cancer diagnosis at the end of the study . MATERIAL S AND METHODS We analyzed serial PSA in participants in the Prostate Cancer Prevention Trial who had an end of study biopsy ( 928 with cancer and 8,620 with negative biopsy ) or an interim diagnosis of prostate cancer ( 671 ) . Linear mixed effects regression models were fit to longitudinal PSA values beginning 1 year after r and omization . RESULTS In subjects with no cancer in the end of study biopsy PSA in the finasteride arm showed a median annual decrease of 2 % [ corrected ] after year 1 , while PSA in the control arm showed an annual increase of 3 % ( p < 0.001 ) . In end of study cases PSA increased annually by 6 % ( placebo ) and 7 % ( finasteride ) . In those with interim diagnoses PSA increased by 11 % ( placebo ) and 15 % ( finasteride ) each year prior to diagnosis . Cases with high grade disease ( Gleason 7 and above ) had greater PSA increases than cases with low grade disease ( p < 0.001 ) . CONCLUSIONS In men who have been receiving finasteride for more than 1 year time varying adjustment factors may be needed to determine whether PSA is in the normal range . In the Prostate Cancer Prevention Trial cohort the adjustment factor required to preserve median PSA increased from 2 at 24 months to 2.5 at 7 years after the initiation of finasteride BACKGROUND Aspirin , other non-steroidal anti-inflammatory drugs ( NSAIDs ) , and statins have been associated with lower risk of prostate cancer and its progression , though results have been inconsistent . METHODS Data from 140 men with prostate cancer enrolled in a Phase 2 clinical trial of selenium to prevent prostate cancer progression were analyzed to determine association between aspirin , other NSAIDs , or statin use with baseline serum prostate-specific antigen ( PSA ) levels and PSA velocity ( rate of PSA change over time ) using repeated measures over an average follow-up time of 3.2 years . Multiple linear regression and mixed effects models were used to model the association of medication use with PSA at baseline and with PSA velocity , respectively . RESULTS Baseline PSA levels were significantly lower in aspirin users compared to non-users ( 5.17 ng/ml vs. 7.58 ng/ml , P = 0.001 ) . This association was statistically significant in never smokers ( aspirin users vs. non-users : 4.19 ng/ml vs. 8.24 ng/ml , P = 0.004 ) but not in ever smokers ( aspirin users vs. non-users : 5.52 ng/ml vs. 7.3 ng/ml , P = 0.101 ) . Statin and other NSAID use was not associated with baseline PSA . Aspirin , statin , or other NSAID use at baseline demonstrated a non-significant negative association with PSA velocity . CONCLUSION These findings support an effect of aspirin use on PSA , particularly among never smokers . However , they do not suggest a protective effect on the disease and support previous findings that aspirin use may mask accurate measurement of PSA warranting consideration of washout procedures prior to testing PURPOSE The 5alpha-reductase inhibitors improve urinary symptoms related to benign prostatic hyperplasia , deter benign prostatic hyperplasia progression and provide prostate cancer chemoprevention . Currently there are a number of 5alpha-reductase inhibitor formularies , including Proscar , generic finasteride and dutasteride . While all formularies decrease serum prostate specific antigen ( a proxy for prostate volume ) , they may not accomplish this to the same degree , which may have dramatic effects on prostate specific antigen kinetics in men changing 5alpha-reductase inhibitor formularies . We examined prostate specific antigen velocity after changes in 5alpha-reductase inhibitor formularies . MATERIAL S AND METHODS We identified patients treated with 2 or more 5alpha-reductase inhibitor formularies who had sufficient prostate specific antigen values to calculate prostate specific antigen velocity during each 5alpha-reductase inhibitor treatment . Patient data were grouped depending on the formularies received . Statistical analysis was done to compare prostate specific antigen velocity at various time points while on different 5alpha-reductase inhibitors . RESULTS Eight men changed from dutasteride to generic finasteride ( group 1 ) , 21 changed from dutasteride to Proscar ( group 2 ) , 49 changed from Proscar to dutasteride ( group 3 ) and 77 changed from Proscar to generic finasteride ( group 4 ) . We noted a significant increase in prostate specific antigen velocity in groups 1 and 2 ( p < 0.05 ) , and 4 ( p < 0.005 ) . The increase was greater than 0.35 ng/ml per year , the common cutoff for prostate biopsy recommendations , in more than a third of patients . CONCLUSIONS Results confirm that changing 5alpha-reductase inhibitors drugs can be associated with a clinical ly significant change in prostate specific antigen velocity . These prostate specific antigen velocity changes could place patients at risk for unnecessary prostate biopsy . Additional prospect i ve studies are warranted |
1,213 | 27,396,268 | However , increased TTC may have a negative prognostic impact , and delays beyond 4 weeks should be avoided .
Timing of chemotherapy for metastatic colorectal cancer does not influence survival .
The optimal timing of chemotherapy in lung cancer is unclear ; however , rapid tumour growth and poor disease prognosis suggest that delays should be avoided wherever possible .
The optimal timing of chemotherapy in ovarian cancer is unclear as available studies are of low level , report inconsistent results and are limited to the post-surgery setting ; however , increased TTC may have a negative prognostic impact ; therefore , delays beyond 4 weeks should be avoided | This review evaluated the association between time-to-chemotherapy ( TTC ) and survival in six priority cancers . | OBJECTIVE : The objective of this study was to identify the risk factors for delays in chemotherapy after rectal cancer surgery and evaluate the effects of delayed therapy on long-term outcomes . We also sought to clarify what time frame should be used to define delayed adjuvant chemotherapy . BACKGROUND : Postoperative complications have been found to influence the timing of chemotherapy in patients with colon cancer . Delays in chemotherapy have been shown to be associated with worse overall and disease-free survival in patients with colorectal cancer , although the timing of delay has not been agreed upon in the literature . STUDY DESIGN : We performed a retrospective review of a prospect ively maintained rectal cancer data base . Univariate analysis was used to identify risk factors for delayed chemotherapy . Kaplan-Meier curves were generated to compare overall and disease-free survival in patients based on complications and timing of chemotherapy . SETTING S : This study was performed at the University of Wisconsin Hospital , Madison , Wisconsin , between 1995 and 2012 . PATIENTS : Patients with rectal cancer who underwent proctectomy with curative intent were included in this study . OUTCOME MEASURES : Timing of chemotherapy , 30-day complications , and 30-day readmissions were the main outcome measures . RESULTS : Postoperative complications and 30-day readmissions were associated with delays in chemotherapy ≥8 weeks after surgery . Patients who received chemotherapy ≥8 weeks postoperatively were found to have worse local and distant recurrence rates and worse overall survival in comparison with patients who received chemotherapy within 8 weeks of surgery . LIMITATIONS : The limitations of this study include its retrospective nature and that it was performed at a single institution . CONCLUSIONS : We found complications and readmissions to be risk factors for delayed chemotherapy . Patients who received therapy ≥8 weeks postoperatively had worse disease-free and overall survival BACKGROUND Whether adjuvant chemotherapy improves survival of patients with non-small-cell lung cancer ( NSCLC ) is not known . We aim ed to compare the effect of adjuvant vinorelbine plus cisplatin versus observation on survival in patients with completely resected NSCLC . METHODS 840 patients with stage IB-IIIA NSCLC from 101 centres in 14 countries were r and omly assigned to observation ( n=433 ) or to 30 mg/m(2 ) vinorelbine plus 100 mg/m(2 ) cisplatin ( n=407 ) . Postoperative radiotherapy was not m and atory and was undertaken according to every centre 's policy . The primary endpoint was overall survival . Analysis was by intention to treat . This trial is registered as an International St and ard R and omised Controlled Trial , number IS RCT N95053737 . FINDINGS 367 patients in the chemotherapy group and 431 in the control group received their assigned treatment . 301 ( 36 % ) patients had stage IB disease , 203 ( 24 % ) had stage II disease , and 325 ( 39 % ) had stage IIIA disease . Tolerance to chemotherapy mainly included neutropenia in 335 ( 92 % ) patients and febrile neutropenia in 34 ( 9 % ) ; seven ( 2 % ) toxic deaths were also recorded . Compliance was greater with cisplatin than with vinorelbine ( median dose intensity 89 % [ range 17 - 108 ] vs 59 % [ 17 - 100 ] ) . After a median follow-up of 76 months ( range 43 - 116 ) , median survival was 65.7 months ( 95 % CI 47.9 - 88.5 ) in the chemotherapy group and 43.7 ( 35.7 - 52.3 ) months in the observation group . Adjusted risk for death was significantly reduced in patients assigned chemotherapy compared with controls ( hazard ratio 0.80 [ 95 % CI 0.66 - 0.96 ] ; p=0.017 ) . Overall survival at 5 years with chemotherapy improved by 8.6 % , which was maintained at 7 years ( 8.4 % ) . INTERPRETATION Adjuvant vinorelbine plus cisplatin extends survival in patients with completely resected NSCLC , better defining indication of adjuvant chemotherapy We report a single-centre prospect i ve audit of 29 lung cancer patients who were awaiting radical ( potentially curative ) radiotherapy . This was the total number assessed as suitable for radical treatment by one consultant during 1999 . At the time of assessment they had been newly diagnosed and staged with a computed tomographic ( CT ) scan of chest . They had a subsequent CT scan prior to starting treatment for the purpose of planning the radiation fields . We have now measured tumour size on the diagnostic scans and compared this with the size on the planning scans . We have documented the delay between diagnostic and planning CT scanning and the total time between first hospital visit and starting treatment . Two patients had progression of symptoms while on the waiting list , making them unfit for radical treatment , and another four had tumour progression on planning CT such that the tumour volume was too large for radical treatment . Therefore , 21 % of potentially curable patients became incurable on the waiting list . The delay between diagnostic and planning CT scans ranged from 18 to 131 days ( median 54 ) , with increases in the cross-sectional tumour size over that period ranging zero to 373 % . The delay between the first hospital visit and starting treatment was 35 - 187 days ( median 94 ) ; between the date of the radiotherapy request and the starting date for treatment it was 23 - 61 days ( median 44 ) . Limited access to specialists is the reason most often advanced for the poor performance of the UK in treating lung cancer . This study demonstrates that , even for the select minority of patients who have specialist referral and are deemed suitable for potentially curative treatment , the outcome is prejudiced by waiting times that allow tumour progression The purpose of this study was to examine the effect on survival of delaying the start of adjuvant chemotherapy for early breast cancer for up to 3 months after surgery . In the nation-wide clinical trials of the Danish Breast Cancer Cooperative Group , 7501 breast cancer patients received chemotherapy within 3 months of surgery between 1977 and 1999 : 352 with classical cyclofosfamide , metotrexate and 5-fluorouracil ( CMF ) ; 6065 with CMF i.v . and 1084 with cyclofosfamide , epirubicin and 5-fluorouracil . For the analysis , the time between surgery and the start of chemotherapy was divided into four strata ( 1–3 , 4 , 5 and 6–13 weeks ) . The results show that within the three groups of chemotherapy , there was an even distribution of known prognostic factors across the four strata of initiation of chemotherapy . There was no pattern indicating a benefit from early start of chemotherapy . No significant interactions were found for subgroups of patients with a poorer prognosis ( many involved lymph nodes , high- grade malignancies or hormone receptor negative disease ) . In conclusion , we have found no evidence for a survival benefit due to early initiation of adjuvant chemotherapy within the first 2–3 months after surgery PURPOSE Theoretically , patients with early breast cancer might benefit from starting adjuvant chemotherapy soon after surgery , and this would have important clinical implication s. We have addressed this question from a large , single-center data base in which the majority of patients received anthracyclines . PATIENTS AND METHODS A total of 1161 patients from a prospect ively maintained data base treated with adjuvant chemotherapy for early breast cancer at the Royal Marsden Hospital ( London , United Kingdom ) , including 686 ( 59 % ) receiving anthracyclines , were retrospectively analyzed . The disease-free survival ( DFS ) and overall survival ( OS ) of the 368 patients starting chemotherapy within 21 days of surgery ( group A ) were compared with those of the 793 patients commencing chemotherapy > or= 21 days after surgery ( group B ) . Median follow-up time was 39 months ( range , 12 to 147 months ) . RESULTS No significant difference in 5-year DFS was found between the two groups overall ( 70 % for group A v 72 % for group B ; P = .4 ) or in any subgroup . Likewise , there was no difference in 5-year OS ( 82 % for group A v 84 % for group B ; P = .2 ) or when the interval to the start of chemotherapy was considered as a continuous variable ( P = .4 ) . CONCLUSION We have been unable to identify any significant survival benefit from starting adjuvant chemotherapy early after surgery , either overall or in any subset of patients BACKGROUND Neither chemotherapy with a single-alkylating agent nor aggressive combination chemotherapy cures advanced stage low- grade non-Hodgkin lymphomas , even when combined with radiotherapy . Our aim was to compare administration of immediate chlorambucil treatment with a policy of delaying chlorambucil until clinical progression necessitated its use , in asymptomatic patients with advanced-stage , low- grade non-Hodgkin lymphoma . METHODS 309 patients with asymptomatic , advanced-stage , low- grade non-Hodgkin lymphomas were recruited from 44 UK centres between Feb 1 , 1981 , and July 31 , 1990 . 158 patients were r and omised to receive immediate systemic therapy with oral chlorambucil 10 mg per day continuously . The remaining 151 were r and omised to an initial policy of observation , with systemic therapy delayed until disease progression . In both groups , local radiotherapy to symptomatic nodes was allowed . FINDINGS Median length of follow-up was 16 years . Overall survival or cause-specific survival did not differ between the two groups ( median overall survival for oral chlorambucil 5.9 [ range 0 - 17.8 ] years and for observation 6.7 [ 0.5 - 18.9 ] years , p=0.84 ; median cause-specific survival 9 [ 0 - 17.8 ] years and 9.1 [ 0.67 - 18.9 ] years , respectively p=0.44 ) . In a multivariate analysis , age younger than 60 years , erythrocyte sedimentation rate ( ESR ) 20 mm/h or less , and stage III disease , conferred significant advantages in both overall survival ( p<0.0001 , 0.03 , and 0.03 , respectively ) and cause-specific survival ( p=0.002 , 0.008 , and 0.001 , respectively ) . In the observation group , at 10 years ' follow-up , 19 patients were alive and had not received chemotherapy . The actuarial chance of not needing chemotherapy ( non-lymphoma deaths censored ) at 10 years was 19 % ( 40 % if older than 70 years ) . INTERPRETATION An initial policy of watchful waiting in patients with asymptomatic , advanced stage low- grade non-Hodgkin lymphoma is appropriate , especially in patients older than age 70 years BACKGROUND Surgery is the primary treatment for patients with stage I , II , or IIIA non-small-cell lung cancer ( NSCLC ) . However , long-term survival of NSCLC patients after surgery alone is largely unsatisfactory , and the role of adjuvant chemotherapy in patient survival has not yet been established . METHODS Between January 1994 and January 1999 , 1209 patients with stage I , II , or IIIA NSCLC were r and omly assigned to receive mitomycin C ( 8 mg/m2 on day 1 ) , vindesine ( 3 mg/m2 on days 1 and 8) , and cisplatin ( 100 mg/m2 on day 1 ) every 3 weeks for three cycles ( MVP group ; n = 606 ) or no treatment ( control group ; n = 603 ) after complete resection . R and omization was stratified by investigational center , tumor size , lymph-node involvement , and the intention to perform radiotherapy . The primary endpoint was overall survival and secondary endpoints were progression-free survival and toxicity associated with adjuvant treatment . Survival curves were analyzed using the log-rank test . All statistical tests were two-sided . RESULTS After a median follow-up time of 64.5 months , there was no statistically significant difference between the two patient groups in overall survival ( hazard ratio = 0.96 , 95 % confidence interval = 0.81 to 1.13 ; P = .589 ) or progression-free survival ( hazard ratio = 0.89 , 95 % confidence interval = 0.76 to 1.03 ; P = .128 ) . Only 69 % of patients received the three planned cycles of MVP . Grade s 3 and 4 neutropenia occurred in 16 % and 12 % , respectively , of patients in the MVP arm . Radiotherapy was completed by 65 % of patients in the MVP arm and by 82 % of patients in the control group . In the multivariable analysis , only disease stage and sex were associated with survival . CONCLUSION This r and omized trial failed to prospect ively confirm a statistically significant role for adjuvant chemotherapy in completely resected NSCLC . Given the poor compliance with the MVP regimen used in this study , future studies should explore more effective treatments The data from two prospect i ve r and omised phase III trials that were initiated by the West Midl and s Ovarian Cancer Study Group ( WMOCSG ) in 1981 and 1986 , recruiting 167 and 195 patients respectively , have been pooled and the survival patterns of the 362 patients treated for advanced epithelial ovarian cancer within clinical trials in the West Midl and s over the 10 year period ( 1981 - 91 ) have been explored . All patients had histologically proven epithelial ovarian cancer and all had residual disease after primary surgery , with the majority having stage III/IV disease . The primary treatment for all patients was debulking surgery followed by platinum-based chemotherapy . Eligible patients were further r and omised to undergo a second debulking operation . The main end point , survival , was assessed using Kaplan-Meier curves and the log-rank test . A Cox proportional hazards model identified performance status ( P = 0.002 ) , residual disease ( P = 0.005 ) and albumin level ( P = 0.04 ) as independent prognostic factors . A multivariate model to predict survival curves for patients with the best and worst prognoses was developed with predicted 5 year survival of 30 % and 3 % for those in the best and worst prognostic groups respectively . The identification of clinical interventions to improve outcome is an urgent matter since the prognosis for patients with advanced ovarian cancer remains poor BACKGROUND On the basis of a previous meta- analysis , the International Adjuvant Lung Cancer Trial was design ed to evaluate the effect of cisplatin-based adjuvant chemotherapy on survival after complete resection of non-small-cell lung cancer . METHODS We r and omly assigned patients either to three or four cycles of cisplatin-based chemotherapy or to observation . Before r and omization , each center determined the pathological stages to include , its policy for chemotherapy ( the dose of cisplatin and the drug to be combined with cisplatin ) , and its postoperative radiotherapy policy . The main end point was overall survival . RESULTS A total of 1867 patients underwent r and omization ; 36.5 percent had pathological stage I disease , 24.2 percent stage II , and 39.3 percent stage III . The drug allocated with cisplatin was etoposide in 56.5 percent of patients , vinorelbine in 26.8 percent , vinblastine in 11.0 percent , and vindesine in 5.8 percent . Of the 932 patients assigned to chemotherapy , 73.8 percent received at least 240 mg of cisplatin per square meter of body-surface area . The median duration of follow-up was 56 months . Patients assigned to chemotherapy had a significantly higher survival rate than those assigned to observation ( 44.5 percent vs. 40.4 percent at five years [ 469 deaths vs. 504 ] ; hazard ratio for death , 0.86 ; 95 percent confidence interval , 0.76 to 0.98 ; P<0.03 ) . Patients assigned to chemotherapy also had a significantly higher disease-free survival rate than those assigned to observation ( 39.4 percent vs. 34.3 percent at five years [ 518 events vs. 577 ] ; hazard ratio , 0.83 ; 95 percent confidence interval , 0.74 to 0.94 ; P<0.003 ) . There were no significant interactions with prespecified factors . Seven patients ( 0.8 percent ) died of chemotherapy-induced toxic effects . CONCLUSIONS Cisplatin-based adjuvant chemotherapy improves survival among patients with completely resected non-small-cell lung cancer In 1977 WE REPORTED our results of an ongoing r and omized clinical trial evaluating early or delayed adjuvant chemotherapy utilizing 5-fluorouracil , cytoxan and prednisone in premenopausal patients with recurrent or advanced breast cancer . At that time the group receiving early systemic chemotherapy was shown to have an improved progression-free interval and appeared to have a trend toward improved survival . The results of subsequent analysis after over 4 more years of follow-up indicate however , that while early employment of systemic chemotherapy does indeed prolong the progression-free interval , and while this advantage has been maintained , there is no survival advantage shown for either group of patients The survival of 229 patients treated with adjuvant i.v . cyclophosphamide , methotrexate , and 5-fluorouracil ( CMF ) after surgery for primary breast cancer was analyzed according to three administration-related factors : total number of cycles received , time elapsed between surgery and start of chemotherapy , and dose intensity of treatment . All parameters were found to be significantly associated with survival of patients in a univariate analysis . Multivariate analysis confirmed the independent prognostic importance of dose intensity and time between surgery and chemotherapy . Although prospect i ve studies are needed to confirm such results , clinicians should be aware that unnecessary treatment delays or dose reductions in adjuvant chemotherapy for breast cancer are probably detrimental to patient survival OBJECTIVE Cytoreductive surgery and platinum-based systemic therapy constitute the st and ard treatment of patients with advanced ovarian cancer . The aim of the present study was to evaluate whether the time interval from surgery to start of chemotherapy has an impact on clinical outcome . METHODS Data of 191 patients with advanced serous ( FIGO III-IV ) ovarian cancer from the prospect i ve multicenter study OVCAD ( OVarian CAncer Diagnosis ) were analyzed . All patients underwent primary surgery followed by platinum-based chemotherapy . RESULTS The 25 % , 50 % , and 75 % quartiles of intervals from surgery to start of chemotherapy were 22 , 28 , and 38 days , respectively ( range , 4 - 158 days ) . Preoperative performance status ( P<0.001 ) , extent of surgery ( P<0.001 ) , and perioperative complications ( P<0.001 ) correlated with intervals from surgery to initiation of chemotherapy . Timing of cytotoxic treatment [ ≤ 28 days versus > 28 days ; hazard ratio ( HR ) 1.73 ( 95 % confidence interval 1.08 - 2.78 ) , P=0.022 ] , residual disease [ HR 2.95 ( 95 % confidence interval 1.87 - 4.67 ) , P<0.001 ] , and FIGO stage [ HR 2.26 ( 95 % confidence interval 1.41 - 3.64 ) , P=0.001 ] were significant prognostic factors for overall survival in multivariate analysis . While the interval from surgery to start of chemotherapy did not possess prognostic significance in patients without postoperative residual disease ( n=121 ) , it significantly correlated with overall survival in patients with postoperative residual disease [ n=70 , HR 2.24 ( 95 % confidence interval 1.08 - 4.66 ) , P=0.031 ] . CONCLUSION Our findings suggest that delayed initiation of chemotherapy might compromise overall survival in patients with advanced serous ovarian cancer , especially when suboptimally debulked BACKGROUND AND AIMS Surgery followed by platinum-taxane chemotherapy is the current st and ard approach to treat advanced ovarian cancer . The impact of the time interval between surgery and initiation of chemotherapy for clinical outcome has not been clarified yet . METHODS Individual patient data analysis of 3326 patients from three prospect i ve r and omised phase III trials conducted between 1995 and 2002 to investigate platinum-taxane based chemotherapy regimens in advanced ovarian cancer . Time to chemotherapy ( TTC ) was analysed and correlated with outcome . RESULTS Median TTC was 19 days ( range 1 - 56 ) . The effect of TTC differed significantly for patients with or without residual disease for progression-free ( PFS ; interaction p=0.004 ) and for overall survival ( OS ; interaction p=0.028 ) . A delayed start of chemotherapy was associated with earlier disease recurrence ( HR 1.038 , 95 % CI 0.973 ; 1.106 , p=0.257 per week delay ) and a significantly decreased OS ( HR 1.087 , 95 % CI 1.005 ; 1.176 p=0.038 ) in patients with no residual tumour after surgery . In contrast , in patients with residual disease , a longer TTC was significantly associated with later progression ( HR 0.931 , 95 % CI 0.895 ; 0.969 , p<0.001 ) and no effect towards OS ( HR 0.983 , 95 % CI 0.940 ; 1.028 , p=0.452 ) . CONCLUSIONS Our results provide evidence that early initiation of chemotherapy might result in slightly improved survival in patients with complete cytoreduction while patients with residual disease after surgery did not benefit from earlier chemotherapy . A prospect i ve study r and omising patients to different time intervals could clarify the definitive relevance of the time between surgery and chemotherapy PURPOSE To evaluate prospect ively in patients with follicular lymphoma and a low tumor burden three therapeutic options : delay of any treatment until clinical ly meaningful progression , immediate treatment with an oral alkylating agent , or treatment with a biologic response modifier , interferon alfa-2b . PATIENTS AND METHODS Newly diagnosed follicular lymphoma patients with a low tumor burden ( n = 193 ) were r and omly assigned to one of three arms : arm 1 , no initial treatment ( n = 66 ) ; arm 2 , prednimustine 200 mg/m2/d for 5 days per month for 18 months ( n = 64 ) ; or arm 3 , interferon alfa 5 MU/d for 3 months then 5 MU three times per week for 15 months ( n = 63 ) . Clinical characteristics were similar in the three arms . RESULTS Overall response rates with prednimustine and interferon alfa were 78 % and 70 % , respectively . The overall response to therapy , when deferred , was similar at 70 % . With a median follow-up duration of 45 months after r and omization , the median freedom-from-treatment ( FFT ) interval was 24 months in arm 1 and the interval of freedom from treatment failure ( FFTF ) was 40 months in arm 2 and 35 months in arm 3 . The median overall survival time was not reached and the overall survival rate at 5 years was 78 % in arm 1 , 70 % in arm 2 , and 84 % in arm 3 . Therefore , deferred treatment does not adversely influence survival at 5 years . Patients who progressed within 1 year had a significantly shorter survival duration ( median , 48 months ) . CONCLUSION Delayed treatment is feasible in patients with follicular lymphoma and a low tumor burden . For patients with early progression , more intensive therapy should be considered . For others , because delay of treatment until significant clinical progression does not seem to hamper the prognosis or subsequent response to treatment , the long-term toxicity of alkylating agents can be reduced OBJECTIVES The non-small cell lung cancer ( NSCLC ) meta- analysis suggested a survival benefit for cisplatin-based chemotherapy when given in addition to surgery , radical radiotherapy or ' best supportive care ' . However , it included many small trials and trials with differing eligibility criteria and chemotherapy regimens . The aim of the Big Lung Trial was therefore to run a large pragmatic trial to confirm the survival benefits seen in the meta- analysis . METHODS In the surgery setting , a total of 381 patients were r and omised to chemotherapy ( C , 192 patients ) or no chemotherapy ( NoC , 189 patients ) . C was three 3-weekly cycles of cisplatin/vindesine , mitomycin/ifosfamide/cisplatin , mitomycin/vinblastine/cisplatin or vinorelbine/cisplatin . RESULTS Chemotherapy was given before surgery in 3 % of patients whilst 97 % received adjuvant chemotherapy . Baseline characteristics were : median age 61 years , 69 % male , 48 % squamous cell , 93 % WHO PS 0 - 1 , 27 % stage I , 38 % stage II , and 34 % stage III . Complete resection was achieved in approximately 95 % of patients . In the C group , 13 % received no chemotherapy , 21 % one or two cycles , and 64 % all three cycles of their prescribed chemotherapy ( 60 % of the latter with no delays or modification ) . 30 % had grade 3/4 toxicity , mainly haematological , nausea/vomiting and neutropenic fever , and six patients were reported as having a treatment-related death . 198 ( 52 % ) of patients have died , but there is currently no evidence of a benefit in overall survival to the C group : HR 1.02 ( 95 % CI 0.77 - 1.35 ) , P = 0.90 ) . CONCLUSIONS This trial has failed to observe a survival benefit with adjuvant chemotherapy following complete resection of stage I-III NSCLC . However , the hazard ratio and 95 % confidence intervals are consistent with the previously reported meta- analysis and two large recently reported trials , which suggest a small survival benefit with cisplatin-based chemotherapy Summary Four hundred and sixty patients with stage II or III breast cancer following regional therapy were treated with an adjuvant combination chemotherapy consisting of fluorouracil , doxorubicin , and cyclophosphamide ( FAC ) . The relationship between the length of disease-free survival and length of delays in initiation of chemotherapy after surgery was evaluated . Patients were divided into four subgroups according to the length of delay in initiation of chemotherapy ( < 10 weeks , 10–13 , 14–17 , and ≥ 18 weeks ) . Overall four year diseasefree survival was 64 % , 68 % , 60 % , and 63 % for patient groups with delays of < 10 weeks , 10–13 , 14–17 , or ≥ 18 weeks respectively ( p = 0.39 ) . There was no trend for longer delay in treatment to be associated with shorter disease-free survival , except in poor prognosis patients Primary surgery followed by platinum‐taxane based chemotherapy has been the st and ard therapy in advanced ovarian cancer . However , the prognostic role of complete and so‐called optimal and suboptimal debulking and its interaction with biological factors has not been not fully defined BACKGROUND Patients with advanced-stage , low-tumour-burden follicular lymphoma have conventionally undergone watchful waiting until disease progression . We assessed whether rituximab use could delay the need for chemotherapy or radiotherapy compared with watchful waiting and the effect of this strategy on quality of life ( QoL ) . METHODS Asymptomatic patients ( aged ≥18 years ) with low-tumour-burden follicular lymphoma ( grade s 1 , 2 , and 3a ) were r and omly assigned central ly ( 1:1:1 ) , by the minimisation approach stratified by institution , grade , stage , and age , to watchful waiting , rituximab 375 mg/m(2 ) weekly for 4 weeks ( rituximab induction ) , or rituximab induction followed by a maintenance schedule of 12 further infusions given at 2-monthly intervals for 2 years ( maintenance rituximab ) . On Sept 30 , 2007 , recruitment into the rituximab induction group was closed and the study was amended to a two-arm study . The primary endpoints were time to start of new treatment and QoL at month 7 ( ie , 6 months after completion of rituximab induction ) . All r and omly assigned patients were included in the analysis of time to start of new treatment on an intention-to-treat basis . The main study is now completed and is in long-term follow-up . The study is registered with Clinical Trials.gov , NCT00112931 . FINDINGS Between Oct 15 , 2004 , and March 25 , 2009 , 379 patients from 118 centres in the UK , Australia , New Zeal and , Turkey , and Pol and were r and omly assigned to watchful waiting or maintenance rituximab . 84 patients were recruited to the rituximab induction group before it was closed early . There was a significant difference in the time to start of new treatment , with 46 % ( 95 % CI 39 - 53 ) of patients in the watchful waiting group not needing treatment at 3 years compared with 88 % ( 83 - 92 ) in the maintenance rituximab group ( hazard ratio [ HR ] 0·21 , 95 % CI 0·14 - 0·31 ; p<0·0001 ) . 78 % ( 95 % CI 69 - 87 ) of patients in the rituximab induction group did not need treatment at 3 years , which was significantly more than in the watchful waiting group ( HR 0·35 , 95 % CI 0·22 - 0·56 ; p<0·0001 ) , but no different compared with the maintenance rituximab group ( 0·75 , 0·41 - 1·34 ; p=0·33 ) . Compared with the watchful waiting group , patients in the maintenance rituximab group had significant improvements in the Mental Adjustment to Cancer scale score ( p=0·0004 ) , and Illness Coping Style score ( p=0·0012 ) between baseline and month 7 . Patients in the rituximab induction group did not show improvements in their QoL compared with the watchful waiting group . There were 18 serious adverse events reported in the rituximab groups ( four in the rituximab induction group and 14 in the maintenance rituximab group ) , 12 of which were grade 3 or 4 ( five infections , three allergic reactions , and four cases of neutropenia ) , all of which fully resolved . INTERPRETATION Rituximab monotherapy should be considered as a treatment option for patients with asymptomatic , advanced-stage , low-tumour-burden follicular lymphoma . FUNDING Cancer Research UK , Lymphoma Research Trust , Lymphoma Association , and Roche Patients with advanced indolent lymphoma often have long survival ( median , 4 to 8 years ) in spite of frequent relapses . The inability of combination chemotherapy or radiation therapy ( RT ) to render patients disease free has led to radically divergent treatment approaches . Initial treatment may vary from aggressive combined modality therapy to no initial treatment . We sought to evaluate these two divergent approaches in a r and omized trial of advanced indolent lymphomas ( nodular , poorly differentiated lymphocytic ; nodular mixed ; diffuse , well-differentiated lymphocytic ; diffuse , intermediately differentiated lymphocytic ; and diffuse , poorly differentiated lymphocytic ) . A total of 104 patients were entered : 44 were r and omly assigned to " watch and wait " in which only carefully defined , limited RT was administered if necessary ; 45 were r and omly assigned to aggressive combined modality treatment with prednisone , methotrexate , doxorubicin , cyclophosphamide , plus etoposide plus mechlorethamine , vincristine , procarbazine , prednisone ( ProMACE-MOPP ) , followed by total nodal irradiation ( TNI ) ; and 15 , with symptoms requiring initial therapy , received the identical combined treatment but were not r and omly assigned . Of 41 evaluable patients on watch and wait , 23 ( 56 % ) have still not required systemic therapy , although 16 ( 39 % ) have received limited RT . Median time to crossover was 34 months . Of 18 patients crossed over , seven of the 16 who completed therapy ( 43 % ) achieved CR ; two ( 11 % ) have relapsed . Histologic progression was seen in six ( 15 % ) of 41 patients on watch and wait without intervening chemotherapy . Of 45 patients r and omly assigned to chemotherapy , 37 ( 82 % ) have completed induction therapy , and 29 of the 37 ( 78 % ) achieved CR . Twenty-five of those 29 patients ( 86 % ) are still in their first remission . Median duration of initial remission has not been reached but will exceed 4 years . ( ABSTRACT TRUNCATED AT 250 WORDS Multicentre r and omized trials have demonstrated equivalent long‐term outcomes for open and laparoscopic resection of colon cancer . Some studies have indicated a possible survival advantage in certain patients undergoing laparoscopic resection . Patients who receive adjuvant chemotherapy in < 8 weeks following surgery can have an improved survival |
1,214 | 9,793,901 | Patients discharged early from hospital to hospital at home following elective surgery expressed greater satisfaction with care than those who remained in hospital .
Carers , however , expressed less satisfaction with hospital at home compared with hospital care .
No statistically significant difference was detected for overall net health costs .
CONCLUSIONS This review does not support the widespread adoption of hospital at home , nor the discontinuation of existing schemes for elderly medical patients , patients who have had elective surgery , or those with a terminal illness .
There is insufficient evidence to determine the effect of hospital at home on patient outcomes , or cost to the health service | BACKGROUND Despite the widespread adoption of hospital at home services it is not known if these services represent an effective way to manage patients , compared with in-patient hospital care . | A r and omised controlled trial has been conducted into the effects of discharging patients from hospital either 48 hours or six to seven days after operations for inguinal hernia and varicose veins . There was no statistically significant difference in major postoperative complications between the two lengths of stay for either of the two conditions . Similarly there was no difference between the two groups of hernia patients in relation to eventual recurrences . There was no significant difference in length of convalescence between long-stay and short-stay patients in full-time occupations . The savings to the statutory services of discharging patients early were estimated at 25.72 pounds per patient . Patients appeared to approve of the type of care they experienced , regardless of length of stay . However , the families of short-stay patients were significantly less enthusiastic in their attitudes towards the policy of early discharge than the families of long-stay patients All admissions to a 1,100-bed Department of Veterans Affairs ( VA ) hospital were screened to identify 171 terminally ill patients with informal caregivers who were then r and omly assigned to VA hospital-based team home care ( HBHC , N = 85 ) or customary care ( N = 86 ) . Patient functioning , and patient and caregiver morale and satisfaction with care were measured at baseline , one month , and six months . Health services utilization was monitored over the six-month study period and converted to cost . Findings included no differences in patient survival , activities of daily living ( ADL ) , cognitive functioning , or morale , but a significant increase in patient ( p = .02 ) and caregiver ( p = .005 ) satisfaction with care at one month . A substitution effect of HBHC was seen . Those in the experimental group used 5.9 fewer VA hospital days ( p = .03 ) , result ing in a $ 1,639 or 47 percent per capita saving in VA hospital costs ( p = .02 ) . As a result , total per capita health care costs , including HBHC , were $ 769 or 18 percent ( n.s . ) lower in the HBHC sample , indicating that expansion of VA HBHC to serve terminally ill veterans would increase satisfaction with care at no additional cost The community health services in Southern Derbyshire , in conjunction with an acute hospital , established a pilot scheme for the early discharge of fractured neck of femur patients from hospital to their own homes . The scheme was evaluated by prospect ively comparing a group of patients using Hospital at Home ( HAH ) and a group receiving hospital care only . The main outcomes measured were the proportion of hospital admissions for fractured neck of femur using HAH , length of stay , patient satisfaction , general health status at discharge as measured by the Nottingham Health Profile , and three-month mortality and readmission rates . Costs were calculated based on prices charged by providers of the services . In the first year of the scheme , 76 ( 18 per cent ) of the 432 hospital admissions for fractured neck of femur fitted the selection criteria and agreed to admission to HAH . Thirty-four patients were identified who were suitable for HAH but not admitted to it . The comparison of the 76 HAH patients and 34 hospital patients revealed that HAH patients were discharged from hospital an average of 7 days earlier ; patients in both groups were satisfied with the care they received ; the general health status of the two groups at discharge was similar , with the exception that HAH patients had better emotional health on discharge from care ; the three-month mortality rate was similar in both groups ( 5 per cent ) ; the readmission rate for HAH patients appeared higher than for hospital patients but this difference was not statistically significant ( 15.8 per cent versus 8.8 per cent , Fisher 's exact test , p = 0.187 ) . ( ABSTRACT TRUNCATED AT 250 WORDS The purpose of this study was to evaluate the impact of a primary home care intervention program on patient outcomes after selected patients were discharged from a short-stay hospital . R and om assignment of 249 frail , elderly patients was made to a group provided with physician-led primary home care , and home assistance service on a 24-hour basis , or to a control group given st and ard care . At r and omization , patients were considerably disabled , had a mean age of 80.5 years , and had a high likelihood of long-stay hospital care . Medical and functional data were essentially the same at baseline for both groups . At 6-months follow-up , significant improvement in instrumental activities of daily living ( P = 0.04 ) and outdoor walking ( P = 0.03 ) , and medical condition was found in the primary care intervention group compared with the controls and less utilization of long-stay hospital facilities was displayed in the team patients ( P < 0.001 ) than in the controls . A selection of elderly , dependent patients can be cared for in their homes after short-stay hospital discharge and benefit from this primary home care intervention program in terms of improved medical and functional outcomes and less long-stay hospitalization The rehabilitation of elderly patients after hip fractures is important : we report a prospect i ve study which compares supported home rehabilitation with management in hospital in two similar groups of patients . Our results show that early discharge from hospital and home rehabilitation produces substantial savings in bed days , and also provides quicker and more effective recovery 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 The opinions of patients and of caring persons ( usually relatives ) were sought in this trial of different methods of providing care for 360 patients after operations for hernia or varicose veins . Analysis of patients ' opinions suggested that day care was the most acceptable of the three types of care examined . The reactions of caring persons did not reveal any major criticisms or disadvantages Alternative systems of care after operations for varicose veins or hernia were compared in a total of 360 selected patients , of whom 121 were allocated to be managed in an acute ward for 48 h , 122 in a convalescent hospital for 48 h and 117 to be discharged directly home to the care of the district nursing sister and general practitioner . There were no deaths or major complications . Anaesthetic or surgical problems caused 5 patients ( 3 convalescent and 2 day care ) to be retained in hospital on the day of operation . Minor complications were recorded in approximately one‐third of the patients . The majority of these were effectively dealt with by the district nursing sister and only one‐third of the complications needed the attention of the general practitioner . Two of the ward patients and 1 of the convalescent patients required readmission to hospital ( 1 per cent in all ) . No significant difference was demonstrated in the medical outcome between the three groups after operation . Day care was the most economical of the three systems of care . Inquiry into the patients ' opinions elicited the highest proportion of favourable responses in the day care group 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 |
1,215 | 27,477,293 | There was no significant difference in minor or severe hypoglycemic events .
Continuous subcutaneous insulin infusion was associated with lower incidence of nocturnal hypoglycemia .
There was no significant difference in the time spent in hypoglycemia .
In children and adults with type 1 diabetes and compared to multiple daily injections , continuous subcutaneous insulin infusion is associated with a modest reduction in glycosylated hemoglobin .
There was no difference in severe or minor hypoglycemia , but likely a lower incidence of nocturnal hypoglycemia with continuous subcutaneous insulin infusion | The relative efficacy of continuous subcutaneous insulin infusion and multiple daily injections in individuals with type 1 diabetes is unclear .
We sought to synthesize the existing evidence about the effect of continuous subcutaneous insulin infusion on glycosylated hemoglobin , hypoglycemic events , and time spent in hypoglycemia compared to multiple daily injections . | OBJECTIVE Insulin pump therapy ( continuous subcutaneous insulin infusion [ CSII ] ) and multiple daily injections ( MDIs ) with insulin glargine as basal insulin and mealtime insulin lispro have not been prospect ively compared in people naïve to either regimen in a multicenter study . We aim ed to help close that deficiency . RESEARCH DESIGN AND METHODS People with type 1 diabetes on NPH-based insulin therapy were r and omized to CSII or glargine-based MDI ( both otherwise using lispro ) and followed for 24 weeks in an equivalence design . Fifty people were correctly r and omized , and 43 completed the study . RESULTS Total insulin requirement ( mean ± SD ) at end point was 36.2 ± 11.5 units/day on CSII and 42.6 ± 15.5 units/day on MDI . Mean A1C fell similarly in the two groups ( CSII −0.7 ± 0.7 % ; MDI −0.6 ± 0.8 % ) with a baseline-adjusted difference of −0.1 % ( 95 % CI −0.5 to 0.3 ) . Similarly , fasting blood glucose and other prepr and ial , postpr and ial , and nighttime self-monitored plasma glucose levels did not differ between the regimens , nor did measures of plasma glucose variability . On CSII , 1,152 hypoglycemia events were recorded by 23 of 28 participants ( 82 % ) and 1,022 in the MDI group by 27 of 29 patients ( 93 % ) ( all hypoglycemia differences were nonsignificant ) . Treatment satisfaction score increased more with CSII ; however , the change in score was similar for the groups . Costs were ∼3.9 times higher for CSII . CONCLUSIONS In unselected people with type 1 diabetes naïve to CSII or insulin glargine , glycemic control is no better with the more expensive CSII therapy compared with glargine-based MDI therapy OBJECTIVE Multiple daily injection ( MDI ) therapy of bolus insulin aspart and basal insulin glargine was compared with continuous subcutaneous insulin infusion ( CSII ) with aspart in type 1 diabetic patients previously treated with CSII . RESEARCH DESIGN AND METHODS One hundred patients were enrolled in a r and omized , multicenter , open-label , crossover study . After a 1-week run-in period with aspart by CSII , 50 subjects were r and omly assigned to MDI therapy ( aspart immediately before each meal and glargine at bedtime ) and 50 subjects continued CSII . After 5 weeks of the first treatment , subjects crossed over to the alternate treatment for 5 weeks . During the last week of each treatment period , subjects wore a continuous glucose monitoring system for 48 - 72 h. RESULTS Mean serum fructosamine levels were significantly lower after CSII therapy than after MDI therapy ( 343 + /- 47 vs. 355 + /- 50 micromol/l , respectively ; P = 0.0001 ) . Continuous glucose monitoring profiles over a 24-h time period showed that glucose exposure was 24 and 40 % lower for CSII than MDI as measured by area under the curve ( AUC ) glucose > /=80 mg/dl ( 1,270 + /- 742 vs. 1,664 + /- 1,039 mg . h . dl(-1 ) ; P < 0.001 ) and AUC glucose > /=140 mg/dl ( 464 + /- 452 vs. 777 + /- 746 mg . h . dl(-1 ) , CSII vs. MDI , respectively ; P < 0.001 ) . Similar percentages of subjects reported hypoglycemic episodes ( CSII : 92 % , MDI : 94 % ) and nocturnal ( 12:00 a.m. to 8:00 a.m. ) hypoglycemic episodes ( CSII : 73 % , MDI : 72 % ) . Major hypoglycemia was infrequent ( CSII : two episodes , MDI : five episodes ) . CONCLUSIONS In a trial of short duration , CSII therapy with insulin aspart result ed in lower glycemic exposure without increased risk of hypoglycemia , as compared with MDI with insulin aspart and glargine OBJECTIVE Effects of pump treatment vs. four times daily injections were explored in children with diabetes with regard to quality of life and impact of disease as well as adverse effects and parameters of metabolic control . METHODS An open , parallel , r and omized controlled prospect i ve comparative study lasting 14 months was completed by 38 type 1 children with diabetes ( age 4 - 16 yr ) following a 3.5-months run-in phase . St and ardized quality -of-life Pediatric Quality of life Inventory ( PedsQL ) and impact of disease scores were obtained every 3.5 months as well as regular medical parameters . Parallel treatment group data and longitudinal within-patient data were analysed for each treatment modality . RESULTS Within-patient comparisons of the two treatment modalities showed significant improvement in PedsQL and impact scores after pump treatment . Treatment group comparisons did not show significant improvement . Pump treatment result ed in decreased symptomatic hypoglycaemia and lowered haemoglobin A1c by 0.22 % after run in . CONCLUSIONS Within-patient comparison suggests that metabolic control , frequency of severe hypoglycaemia ( a threefold decrease ) , quality of life and impact of disease scores are improved by pump treatment in comparison to regular treatment with four daily insulin injections AIMS The goal of the study was to determine whether continuous subcutaneous insulin infusion ( CSII ) differs from a multiple daily injection ( MDI ) regimen based on neutral protamine hagedorn ( NPH ) as basal insulin with respect to glycaemic control and quality of life in people with Type 1 diabetes . METHODS The 5-Nations trial was a r and omized , controlled , crossover trial conducted in 11 European centres . Two hundred and seventy-two patients were treated with CSII or MDI during a 2-month run-in period followed by a 6-month treatment period , respectively . The quality of glycaemic control was assessed by HbA(1c ) , blood glucose values , and the frequency of hypoglycaemic events . For the evaluation of the quality of life , three different self-report question naires have been assessed . RESULTS CSII treatment result ed in lower HbA(1c ) ( 7.45 vs. 7.67 % , P < 0.001 ) , mean blood glucose level ( 8.6 vs. 9.4 mmol/l , P < 0.001 ) and less fluctuation in blood glucose levels than MDI ( + /- 3.9 vs. + /- 4.3 mmol/l , P < 0.001 ) . There was a marked reduction in the frequency of hypoglycaemic events using CSII compared with MDI , with an incidence ratio of 1.12 [ 95 % confidence interval ( CI ) : 1.08 - 1.17 ] and 2.61 ( 95 % CI : 1.59 - 4.29 ) for mild and severe hypoglycaemia , respectively . The overall score of the diabetes quality of life question naire was higher for CSII ( P < 0.001 ) , and an improvement in pump users ' perception of mental health was detected when using the SF-12 question naire ( P < 0.05 ) . CONCLUSION CSII usage offers significant benefits over NPH-based MDI for individuals with Type 1 diabetes , with improvement in all significant metabolic parameters as well as in patients ' quality of life . Additional studies are needed to compare CSII with glargine- and detemir-based MDI 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 Recently developed technologies for the treatment of type 1 diabetes mellitus include a variety of pumps and pumps with glucose sensors . METHODS In this 1-year , multicenter , r and omized , controlled trial , we compared the efficacy of sensor-augmented pump therapy ( pump therapy ) with that of a regimen of multiple daily insulin injections ( injection therapy ) in 485 patients ( 329 adults and 156 children ) with inadequately controlled type 1 diabetes . Patients received recombinant insulin analogues and were supervised by expert clinical teams . The primary end point was the change from the baseline glycated hemoglobin level . RESULTS At 1 year , the baseline mean glycated hemoglobin level ( 8.3 % in the two study groups ) had decreased to 7.5 % in the pump-therapy group , as compared with 8.1 % in the injection-therapy group ( P<0.001 ) . The proportion of patients who reached the glycated hemoglobin target ( < 7 % ) was greater in the pump-therapy group than in the injection-therapy group . The rate of severe hypoglycemia in the pump-therapy group ( 13.31 cases per 100 person-years ) did not differ significantly from that in the injection-therapy group ( 13.48 per 100 person-years , P=0.58 ) . There was no significant weight gain in either group . CONCLUSIONS In both adults and children with inadequately controlled type 1 diabetes , sensor-augmented pump therapy result ed in significant improvement in glycated hemoglobin levels , as compared with injection therapy . A significantly greater proportion of both adults and children in the pump-therapy group than in the injection-therapy group reached the target glycated hemoglobin level . ( Funded by Medtronic and others ; Clinical Trials.gov number , NCT00417989 . OBJECTIVE This study assesses the effects of insulin pump therapy on diabetes control and family life in children 1 - 6 years old with type 1 diabetes . RESEARCH DESIGN AND METHODS Twenty-six children with type 1 diabetes for > /=6 months were r and omly assigned to current therapy ( two or three shots per day using NPH insulin and rapid-acting analog ) or continuous subcutaneous insulin infusion ( CSII ) for 6 months . After 6 months , current therapy subjects were offered CSII . Changes in HbA(1c ) , mean blood glucose ( MBG ) , hypoglycemia frequency , diabetes-related quality of life ( QOL ) , and parental adjustment were recorded . RESULTS Eleven subjects from each group completed the trial ( age 46.3 + /- 3.2 months [ means + /- SE ] ) . At baseline , there were no differences between groups in HbA(1c ) , MBG , age , sex , diabetes duration , or parental QOL . Mean HbA(1c ) , MBG , and parental QOL were similar between groups at 6 months . Mean HbA(1c ) and MBG did not change from baseline to 6 months in either group . The frequency of severe hypoglycemia , ketoacidosis , or hospitalization was similar between groups at any time period . Subjects on CSII had more fasting and predinner mild/moderate hypoglycemia at 1 and 6 months . Diabetes-related QOL improved in CSII fathers from baseline to 6 months . Psychological distress increased in current therapy mothers from baseline to 6 months . All subjects continued CSII after study completion . CONCLUSIONS CSII is safe and well tolerated in young children with diabetes and may have positive effects on QOL . CSII did not improve diabetes control when compared with injections , despite more mild/moderate hypoglycemia . The benefits and realistic expectations of CSII should be thoroughly examined before starting this therapy in very young children OBJECTIVE To compare glycemic patterns by mode of therapy in children with type 1 diabetes mellitus using the Continuous Glucose Monitoring System ( CGMS ) . DESIGN Open r and omized crossover comparing 3(1/2 ) months of multiple daily injections ( MDI ) and continuous subcutaneous insulin infusion ( CSII ) . SETTING Tertiary care , university-affiliated medical center . Patients Twenty-three children and adolescents with type 1 diabetes mellitus . INTERVENTIONS The CGMS was applied for 72 hours after 1 month and at the end of each study arm . MAIN OUTCOME MEASURES Hemoglobin A(1c ) levels and glucose level profiles were compared between the 2 study arms and the 2 sensor applications for each arm . RESULTS The arms were similar for mean ( SD ) hemoglobin A(1c ) levels ( CSII , 8.0 % [ 0.8 % ] ; and MDI , 8.2 % [ 0.8 % ] ) and glucose levels . Areas under the curve were significantly larger during MDI for nocturnal and 24-hour hypoglycemia ( P = .01 and .04 , respectively ) and for postpr and ial hypoglycemia and hyperglycemia ( P = .03 and .05 , respectively ) . The rate of hyperglycemia increased during CSII ( P = .03 ) , but 24-hour duration and area under the curve for hyperglycemia were similar . Compared with the first CGMS reading in each arm , the second had a longer mean duration of postpr and ial within-target glucose levels ( P = .04 ) , tendency for lower rate of diurnal hypoglycemic events ( P = .1 ) , shorter duration of nocturnal hypoglycemia ( P = .05 ) , and smaller 24-hour area under the curve for hypoglycemia ( P = .04 ) . CONCLUSIONS Intensive treatment with CSII seemed to be associated with slightly better prebreakfast , postpr and ial , and within-target glucose profiles than MDI , as well as a smaller area under the curve for hypoglycemia . Lower hypoglycemia-related variables in the second sensor reading in each arm indicate that the CGMS may serve as an educational tool to decrease the rate and magnitude of hypoglycemia OBJECTIVE The efficacy of the insulin analogs now available for multiple daily injection ( MDI ) and continuous subcutaneous insulin infusion ( CSII ) therapy in type 1 diabetes has not yet been established in pediatric patients . Our principal aim in this short-term study was to compare the efficacy of CSII to MDI with glargine in lowering HbA(1c ) levels in children and adolescents with type 1 diabetes . RESEARCH DESIGN AND METHODS Thirty-two youth with type 1 diabetes ( age 8 - 21 years ) were r and omly assigned to receive either MDI treatment with once-daily glargine and premeal/snack insulin aspart or CSII with insulin aspart . Dose titration in both groups was based on home self-monitored blood glucose measurements and monthly HbA(1c ) . HbA(1c ) , total daily insulin dose ( TDD ) , self-monitored blood glucose readings , and adverse events were compared after 16 weeks of therapy . RESULTS While there was no significant change in the glargine group ( HbA(1c ) 8.2 % at baseline vs. 8.1 % at 16 weeks ) , youth r and omized to CSII had a sharp reduction in HbA(1c ) levels , from 8.1 to 7.2 % after 16 weeks of therapy ( P < 0.02 vs. baseline and < 0.05 vs. glargine group ) . TDD was unchanged in the glargine group , but significantly dropped with CSII ( 1.4 units/kg at baseline vs. 0.9 units/kg at 16 weeks , P < 0.01 ) . Both groups had similar basal doses and insulin-to-carbohydrate ratios . Fasting self-monitored blood glucose was similar in both groups , but lunch , dinner , and bedtime readings were significantly lower in the CSII group ( P < 0.01 ) . CONCLUSIONS Lower HbA(1c ) and premeal glucose levels were more achievable in this short-term study with CSII than with glargine-based MDI treatment . CSII is an efficacious treatment to improve metabolic control in youth with type 1 diabetes AIMS To investigate the efficacy of sensor-augmented pump therapy vs. multiple daily injection therapy in patients with suboptimally controlled Type 1 diabetes . METHODS In this investigator-initiated multi-centre trial ( the Eurythmics Trial ) in eight outpatient centres in Europe , we r and omized 83 patients with Type 1 diabetes ( 40 women ) currently treated with multiple daily injections , age 18 - 65 years and HbA(1c ) ≥ 8.2 % ( ≥ 66 mmol/mol ) to 26 weeks of treatment with either a sensor-augmented insulin pump ( n = 44 ) ( Paradigm ( ® ) REAL-Time ) or continued with multiple daily injections ( n = 39 ) . Change in HbA(1c ) between baseline and 26 weeks , sensor-derived endpoints and patient-reported outcomes were assessed . RESULTS The trial was completed by 43/44 ( 98 % ) patients in the sensor-augmented insulin pump group and 35/39 ( 90 % ) patients in the multiple daily injections group . Mean HbA(1c ) at baseline and at 26 weeks changed from 8.46 % ( SD 0.95 ) ( 69 mmol/mol ) to 7.23 % ( SD 0.65 ) ( 56 mmol/mol ) in the sensor-augmented insulin pump group and from 8.59 % ( SD 0.82 ) ( 70 mmol/mol ) to 8.46 % ( SD 1.04 ) ( 69 mmol/mol ) in the multiple daily injections group . Mean difference in change in HbA(1c ) after 26 weeks was -1.21 % ( 95 % confidence interval -1.52 to -0.90 , P < 0.001 ) in favour of the sensor-augmented insulin pump group . This was achieved without an increase in percentage of time spent in hypoglycaemia : between-group difference 0.0 % ( 95 % confidence interval -1.6 to 1.7 , P = 0.96 ) . There were four episodes of severe hypoglycaemia in the sensor-augmented insulin pump group and one episode in the multiple daily injections group ( P = 0.21 ) . Problem Areas in Diabetes and Diabetes Treatment Satisfaction Question naire scores improved in the sensor-augmented insulin pump group . CONCLUSIONS Sensor augmented pump therapy effectively lowers HbA(1c ) in patients with Type 1 diabetes suboptimally controlled with multiple daily injections BACKGROUND In the interest of preserving residual insulin secretory capacity present at the time of diagnosis with type 1 diabetes ( T1D ) , we compared the efficacy of starting insulin pump therapy at diagnosis with st and ard multiple daily insulin injections ( MDIs ) . METHODS We conducted a prospect i ve , r and omized , pilot trial comparing MDI therapy with continuous subcutaneous insulin therapy ( pump therapy ) in 24 patients , 8 - 18 years old , with newly diagnosed T1D . Subjects were evaluated at enrollment and 1 , 3 , 6 , 9 , and 12 months after initial diagnosis of T1D . Preservation of insulin secretion , measured by mixed-meal-stimulated C-peptide secretion , was compared after 6 and 12 months of treatment . Between-group differences in glycosylated hemoglobin ( HbA1c ) , continuous glucose sensor data , insulin utilization , anthropometric measures , and patient satisfaction with therapy were also compared at multiple time points . RESULTS Initiation of pump therapy within 1 month of diagnosis result ed in consistently higher mixed-meal tolerance test-stimulated C-peptide values at all time points , although these differences were not statistically significant . Nonetheless , improved glycemic control was observed in insulin pump-treated subjects ( more time spent with normoglycemia , better mean HbA1c ) , and pump-treated subjects reported comparatively greater satisfaction with route of treatment administration . CONCLUSIONS Initiation of insulin pump therapy at diagnosis improved glycemic control , was well tolerated , and contributed to improved patient satisfaction with treatment . This study also suggests that earlier use of pump therapy might help to preserve residual β-cell function , although a larger clinical trial would be required to confirm this OBJECTIVE Our goals were to determine if continuous subcutaneous insulin infusion ( CSII ) , compared with those continuing multiple daily injections ( MDIs ) , can be safely used in young children , if those on CSII will have superior glycemic control , if subjects using CSII will have less hypoglycemia for their level of control , and if families using CSII will report an improved quality of life . RESEARCH DESIGN AND METHODS We conducted a r and omized 1-year feasibility trial comparing CSII with continuing MDIs in preschool children with a history of type 1 diabetes for at least 6 months ' duration . Prospect i ve outcomes included measures of overall glycemic control ( HbA1c and continuous glucose monitoring system ) , the incidence of severe hypoglycemia and diabetic ketoacidosis , the percent of glucose values below 3.9 mmol/l , and the parents ' report of quality of life . RESULTS The 19 subjects ' ages ranged from 1.7 to 6.1 ( mean 3.6 ) years , duration of diabetes ranged from 0.6 to 2.6 ( mean 1.4 ) years , and baseline HbA1c ranged from 6.7 to 9.6 % ( mean 7.9 % ) . Seven subjects were male . Nine subjects were r and omized to start CSII and 10 to continue on MDI . All baseline characteristics were well balanced . Overall metabolic control , diabetes quality of life , and the incidence of hypoglycemia were similar in the two groups . No subject had diabetic ketoacidosis , while one subject in each group had an episode of severe hypoglycemia . No CSII subject discontinued using the pump during or after the study . CONCLUSIONS CSII can be a safe and effective method to deliver insulin in young children AIMS The aim of this case-control study was to compare quality of life ( QoL ) and treatment satisfaction in adults with Type 1 diabetes ( T1DM ) treated with either continuous subcutaneous insulin infusion ( CSII ) or multiple daily injections ( MDI ) . METHODS Consecutive patients aged between 18 and 55 years , and attending diabetes clinics for a routine visit , completed the Diabetes-Specific Quality -of-Life Scale ( DSQOLS ) , the Diabetes Treatment Satisfaction Question naire ( DTSQ ) and the SF-36 Health Survey ( SF-36 ) . Case ( CSII ) and control subjects ( MDI ) were recruited in a 1 : 2 ratio . RESULTS Overall , 1341 individuals were enrolled by 62 diabetes clinics ; 481 were cases and 860 control subjects . Cases had a longer diabetes duration and were more likely to have eye and renal complications . Age , school education , occupation and HbA(1c ) were similar . Of control subjects , 90 % followed glargine-based MDI regimens and 10 % used NPH-based MDI regimens . On multivariate analysis , after adjusting for socioeconomic and clinical characteristics , scores in the following areas of the DSQOLS were higher in cases than control subjects : diet restrictions ( beta = 5.96 ; P < 0.0001 ) , daily hassles ( beta = 3.57 ; P = 0.01 ) and fears about hypoglycaemia ( beta = 3.88 ; P = 0.006 ) . Treatment with CSII was also associated with a markedly higher DTSQ score ( beta = 4.13 ; P < 0.0001 ) compared with MDI . Results were similar when CSII was compared separately with glargine- or NPH-based MDI regimens . CONCLUSIONS This large , non-r and omized , case-control study suggests quality of life gains deriving from greater lifestyle flexibility , less fear of hypoglycaemia , and higher treatment satisfaction , when CSII is compared with either glargine-based or NPH-based MDI regimens BACKGROUND A 16-week , two-site study evaluated outcomes for a new device ( the Paradigm 722 System , Medtronic MiniMed , Northridge , CA ) that combines a " smart " continuous subcutaneous insulin infusion ( CSII ) pump with real-time ( RT ) continuous glucose monitoring ( CGM ) and CareLinktrade mark data management software ( DMS ) . METHODS CSII-naive adults with type 1 diabetes in suboptimal control ( mean glycosylated hemoglobin [ A1C ] = 8.6 % ) were r and omized to the control arm , consisting of multiple daily injections ( MDI ) and self-monitoring of blood glucose ( SMBG ) , or the study arm ( CSII with RT-CGM as an adjunct to SMBG ) . Participants ( n = 28 ) completed the vali date d Insulin Delivery System Rating Question naire ( IDSRQ ) and the parallel Blood Glucose ( BG ) Monitoring System Rating Question naire ( BGMSRQ ) at study start and end . Participants in the study arm ( n = 14 ) also completed newly developed User Acceptance Question naires ( UAQs ) for CSII , RT-CGM , and DMS at study end . RESULTS A1C reduction from study start to end was significant ( P < 0.05 ) in both arms ( -1.7 % for study arm;-1.0 % for control arm ) ; there was no significant change in weight in either arm . The IDSRQ showed significantly ( P < 0.05 ) greater benefit for the study arm in convenience , acceptability of BG monitoring requirements , BG control efficacy , diabetes worries , and interpersonal hassles , as well as higher overall satisfaction/preference . The BGMSRQ showed significantly ( P < 0.05 ) greater benefit for the study arm in the BG monitoring system 's ability to help manage glycemic control and less interest in changing to another BG monitoring system . The Study Arm UAQs showed positive ratings of system features . CONCLUSIONS Several patient-reported outcomes were significantly more positive in the study arm than the control arm ; none was significantly more positive in the control arm . The features of the integrated RT-CGM/CSII system were frequently used and highly rated by participants , with high user satisfaction A study was performed to examine the feasibility of achieving long periods of near-normoglycaemia in patients with diabetes mellitus by giving a continuous subcutaneous infusion of insulin solution from a miniature , battery-driven , syringe pump . Twelve insulin-dependent diabetics had their insulin pumped through a subcutaneously implanted , fine nylon cannula ; the basal infusion rate was electronically stepped up eightfold before meals . The blood glucose profile of these patients was closely monitored during the 24 hours of the subcutaneous infusion and compared with the profile on a control day , when the patients were managed with their usual subcutaneous insulin . Diet and exercise were st and ardised on both days . In five out of 14 studies the subcutaneous insulin infusion significantly lowered the mean blood glucose concentration without producing hypoglycaemic symptoms ; in another six patients the mean blood glucose concentration was maintained . As assessed by the M value the level of control was statistically improved in six out of 14 studies by the infusion method and maintained in six other patients . To assess the effects of blood glucose control on diabetic microvascular disease it will be necessary to achieve long-term normoglycaemia in selected diabetics . The results of this preliminary study suggest that a continuous subcutaneous insulin infusion may be a means of maining physiological glucose concentrations in diabetics . Though several problems remain -- for example , in determining the rate of infusion -- longer-term studies with the miniature infusion pumps are now needed Intensive therapy for type 1 diabetes mellitus ( DM ) is usually provided by either multiple daily injections of insulin ( MDI ) or by insulin pump ( continuous subcutaneous insulin infusion CSII ) . We design ed an open , r and omized , crossover trial to compare CSII with MDI for glycemic control , dose requirements , weight change , incidence of adverse events , quality of life and satisfaction in adolescents OBJECTIVE To compare the efficacy and feasibility of continuous subcutaneous insulin infusion ( CSII ) with multiple daily insulin injections ( MDI ) in children with type 1 diabetes . METHODS The study sample included 23 children ( 10 males ) aged 9.4 to 13.9 years with type 1 diabetes . An open r and omized crossover design was used to compare 3.5 months of CSII to 3.5 months of MDI therapy for the following variables : diabetic control , incidence of adverse events , daily insulin requirement , body mass index st and ard deviation scores , treatment satisfaction , and quality of life . RESULTS The changes in HbA(1c ) and fructoseamine values were similar in the 2 arms over time . At the end of the study , mean HbA(1c ) level measured 8.05 + /- 0.78 % . There were no differences between the treatment modes in frequency of symptomatic hypoglycemic or hyperglycemic events . There was 1 event of severe hypoglycemia during pump therapy and 3 during MDI , yielding a rate of 0.26 events per patient-year . There were no episodes of diabetic ketoacidosis . Body mass index st and ard deviation scores decreased during CSII and increased during MDI , as did mean insulin dose . Patients expressed a higher treatment satisfaction from CSII than MDI , although there was no difference in quality of life between the 2 modes . CONCLUSIONS Intensive insulin therapy by either insulin pump or MDI is safe in children and young adolescents with type 1 diabetes , with similar diabetes control and a very low rate of adverse events . We suggest that both modes be available to the diabetic team to better tailor therapy OBJECTIVE To compare glycemic control , safety , and parental satisfaction in preschool-aged diabetic children r and omized to treatment either with continuous subcutaneous insulin infusion ( CSII ) or intensive insulin injection therapy . STUDY DESIGN This clinical trial enrolled 42 patients < 5 years of age who had been diagnosed with diabetes for at least 12 months . Children were r and omly assigned to CSII ( n = 21 ) or intensive insulin injection therapy ( n = 21 ) . Hemoglobin A1c ( HbA1c ) level was measured at baseline , 3 , and 6 months . Secondary outcomes included severe hypoglycemic events , meter-detected hypoglycemia , blood sugar variability , body mass index ( BMI ) , and satisfaction with therapy . RESULTS Thirty-seven patients completed 6 months of therapy . There was a significant decrease in HbA1c during the study period for both groups ( from 8.9 % + /- 0.6 % to 8.6 % + /- 0.6 % at 3- and 6-month visits ) . At 3 months , children using pumps had a significantly lower HbA1c than the injection group ( 8.4 % vs 8.8 % ) ; however , by 6 months the two groups were similar ( 8.5 % vs 8.7 % ) . No differences in pre-meal blood sugar variabilities were seen between groups . Children on pumps had increases in the number of meter-detected episodes of hypoglycemia . Pump therapy was safe and well tolerated . No episodes of ketoacidosis occurred in either group , whereas one hypoglycemic seizure occurred in each group . Parents reported satisfaction with CSII , with 95 % of families continuing on CSII beyond the 6-month study period . CONCLUSION Pump therapy in preschool-aged children was not associated with clinical ly significant differences in glycemic control as compared with intensive injection therapy . The rationale for initiating CSII in this age group should be based on patient selection and lifestyle preference OBJECTIVE To compare medical , nutritional , and psychosocial outcomes of continuous subcutaneous insulin infusion ( CSII ) therapy and multiple daily insulin injections ( MDI ) in preschoolers with type 1 diabetes mellitus ( T1DM ) in a r and omized controlled trial . STUDY DESIGN Sixteen children ( mean age 4.4 + /- 0.7 yr , range 3.1 - 5.3 yr ) with T1DM were r and omly assigned to CSII or MDI . Hemoglobin A1c ( HbA1c ) was measured monthly for 6 months . Glucose variability was measured at baseline and at 6 months using continuous blood glucose sensing . Quality of life , adverse events , and nutrition information were assessed . RESULTS Parents of the CSII group reported a significant decrease in diabetes-related worry , while parents of the MDI group reported an increased frequency of stress associated with their child 's medical care . Mean HbA1c levels from baseline ( CSII 8.3 + /- 1.4 % , MDI 8.0 + /- 0.8 % ) to 6 months ( CSII 8.4 + /- 0.8 % , MDI 8.2 + /- 0.4 % ) remained stable , and group differences were not significant . There were no significant group differences in duration of hypo- or hyperglycemic events or frequency of adverse events . CONCLUSION ( S ) For young children with T1DM , CSII therapy is comparable to MDI therapy with regard to glucose control but is associated with higher treatment satisfaction and improved quality of life AIMS The superiority of continuous subcutaneous insulin infusion ( CSII ) over multiple daily injections ( MDI ) with glargine is uncertain . In this r and omized cross-over study , we compared CSII and MDI with glargine in patients with Type 1 diabetes well controlled with CSII . The primary end-point was glucose variability . METHODS Thirty-nine patients [ 38.1 + /- 9.3 years old ( mean + /- sd ) , diabetes duration 16.6 + /- 8.2 years , glycated haemoglobin ( HbA(1c ) ) 7.6 + /- 0.8 % ] , already on CSII for at least 6 months , were r and omly assigned to CSII with lispro or MDI with lispro and glargine . After 4 months they were switched to the alternative treatment . During the last month of each treatment blood glucose variability was analysed using glucose st and ard deviation , mean amplitude of glycaemic excursions ( MAGE ) , lability index and average daily risk range ( ADRR ) . As secondary end-points we analysed blood glucose profile , HbA(1c ) , number of episodes of hypo- and hyperglycaemia , lipid profile , free fatty acids ( FFA ) , growth hormone and treatment satisfaction . RESULTS During CSII , glucose variability was 5 - 12 % lower than during MDI with glargine . The difference was significant only before breakfast considering glucose st and ard deviation ( P = 0.011 ) , significant overall using MAGE ( P = 0.016 ) and lability index ( P = 0.005 ) and not significant using ADRR . Although HbA(1c ) was similar during both treatments , during CSII blood glucose levels were significantly lower , hyperglycaemic episodes were fewer , daily insulin dose was less , FFA were lower and treatment satisfaction was greater than during MDI with glargine . The frequency of hypoglycaemic episodes was similar during both treatments . CONCLUSIONS During CSII , glucose variability is lower , glycaemic control better and treatment satisfaction higher than during MDI with glargine In this study k]glycemic control k]diabetes care indices and quality of life ( QoL ) were assessed in 2 groups of newly diagnosed Type 1 diabetic subjects < 6 yr old who were r and omized to multiple daily injections with ( Group A ) or without ( Group B ) an indwelling catheter . Group A [ 12 males (M)/8 females ( F ) , mean age 3.2±1.4yr ] and Group B ( 9M/11F , mean age 3.9±1.8 yr ) were evaluated at baseline and after 6 and 12 months of treatment . No significant difference was observed in metabolic control ( glycosylated hemoglobin ) or in the number of hypoglycemic events between the groups . Patients in Group A had a greater number of daily insulin injections , monitored blood glucose more frequently and had a lower total daily insulin dose per kg ( p<0.05 ) . QoL was better in group A. At the end of the study 30 % of group A patients progressed to continuous sc insulin infusion ( CSII ) , while no child in Group B switched to a different insulin regimen . Based on these findings , indwelling catheter therapy may be helpful for selected CSII c and i date OBJECTIVE To determine whether impaired awareness of hypoglycemia ( IAH ) can be improved and severe hypoglycemia ( SH ) prevented in type 1 diabetes , we compared an insulin pump ( continuous subcutaneous insulin infusion [ CSII ] ) with multiple daily injections ( MDIs ) and adjuvant real-time continuous glucose monitoring ( RT ) with conventional self-monitoring of blood glucose ( SMBG ) . RESEARCH DESIGN AND METHODS A 24-week 2 × 2 factorial r and omized controlled trial in adults with type 1 diabetes and IAH was conducted . All received comparable education , support , and congruent therapeutic targets aim ed at rigorous avoidance of biochemical hypoglycemia without relaxing overall control . Primary end point was between-intervention difference in 24-week hypoglycemia awareness ( Gold score ) . RESULTS A total of 96 participants ( mean diabetes duration 29 years ) were r and omized . Overall , biochemical hypoglycemia ( ≤3.0 mmol/L ) decreased ( 53 ± 63 to 24 ± 56 min/24 h ; P = 0.004 [ t test ] ) without deterioration in HbA1c . Hypoglycemia awareness improved ( 5.1 ± 1.1 to 4.1 ± 1.6 ; P = 0.0001 [ t test ] ) with decreased SH ( 8.9 ± 13.4 to 0.8 ± 1.8 episodes/patient-year ; P = 0.0001 [ t test ] ) . At 24 weeks , there was no significant difference in awareness comparing CSII with MDI ( 4.1 ± 1.6 vs. 4.2 ± 1.7 ; difference 0.1 ; 95 % CI −0.6 to 0.8 ) and RT with SMBG ( 4.3 ± 1.6 vs. 4.0 ± 1.7 ; difference −0.3 ; 95 % CI −1.0 to 0.4 ) . Between-group analyses demonstrated comparable reductions in SH , fear of hypoglycemia , and insulin doses with equivalent HbA1c . Treatment satisfaction was higher with CSII than MDI ( 32 ± 3 vs. 29 ± 6 ; P = 0.0003 [ t test ] ) , but comparable with SMBG and RT ( 30 ± 5 vs. 30 ± 5 ; P = 0.79 [ t test ] ) . CONCLUSIONS Hypoglycemia awareness can be improved and recurrent SH prevented in long-st and ing type 1 diabetes without relaxing HbA1c . Similar biomedical outcomes can be attained with conventional MDI and SMBG regimens compared with CSII/RT , although satisfaction was higher with CSII CONTEXT The effect of glycemic control on persisting albuminuria remains unclear . Insulin delivery and glucose variability may be important . OBJECTIVE This study aim ed to investigate the effect of 1-year treatment with sensor-augmented insulin pump ( SAP ) or multiple daily injections ( MDIs ) on albuminuria . DESIGN , PATIENTS , AND METHODS This was a r and omized controlled open-label parallel trial composed of 60 patients with type 1 diabetes with a history of albuminuria and on stable renin-angiotensin system inhibition , were r and omly assigned to SAP or MDI . Urine albumin creatinine ratio ( UACR ) was measured in three urine sample s at all visits . Glucose variability and glomerular filtration rate ( (51)Cr-EDTA-GFR ) were measured at beginning and study end . Using linear mixed model , change in UACR between groups was analyzed as intention to treat . MAIN OUTCOME MEASURE Change in UACR was measured . RESULTS Fifty-five patients ( SAP , n = 26 ; MDI , n = 29 ) completed the study . Diabetes duration ( mean ± SD , 33 ± 12 y ) , UACR ( geometric mean , 99 mg/g ; interquartile range , 37 - 233 mg/g ) , (51)Cr-EDTA-GFR ( 94 ± 22 mL/min/1.73m(2 ) ) , glycosylated hemoglobin ( HbA1c ) ( 9.0 ± 1.1 % ) , glucose variability ( calculated as SD ) , 4.0 ± 1.0 mmol/l ; no-group differences ( P ≥ .06 for all ) . After 1 year , change in UACR was mean , -13 % ; 95 % confidence interval , -39 to 22 with SAP vs mean , 30 % ; 95 % CI , -12 to 92 % on MDI treatment ( unadjusted P = .051 ; adjusted for HbA1c , P = .04 ) . HbA1c decreased 1.3 ± 1.0 vs 0.6 ± 1.0 % ( P = .013 ) , glucose variability decreased 0.9 ± 1.1 vs 0.3 ± 1.0 mmol/L ( P = .04 ) , and (51)Cr-EDTA-GFR declined 5.6 ± 9.6 vs 3.4 ± 13 mL/min/1.73m(2 ) ( P = .50 ) with SAP vs MDI treatment . There were no changes in blood pressure ( P ≥ .27 ) . CONCLUSION SAP treatment reduced UACR in a r and omized controlled trial in type 1 diabetes patients with a history of albuminuria on stable renin-angiotensin system inhibition . Significance was reached after adjustment . SAP treatment reduced HbA1c and glucose variability ( calculated as SD ) |
1,216 | 24,622,604 | None of the review articles revealed any difference in the frequency of severe hemorrhagic events .
Adults with an indication for long-term oral anticoagulation benefit from self-management , as compared to st and ard treatment with management of dosing by a physician . | BACKGROUND Properly dosed oral anticoagulation effectively prevents thromboembolic events .
It is unclear whether adult patients with an indication for long-term oral anticoagulation can benefit from self-management in terms of patient-oriented endpoints and improved coagulation values . | CONTEXT Control of oral anticoagulation therapy has been reported to often be inadequate . Previous retrospective investigations suggest that patients ' self-adjustment of oral anticoagulants may lead to improved control . OBJECTIVE To investigate the effects of patients ' self-management of oral anticoagulation therapy on accuracy of control and measures of treatment-related quality of life . DESIGN R and omized , single-blind , multicenter trial . SETTING AND PARTICIPANTS A total of 179 patients receiving long-term oral anticoagulation treatment were enrolled at 5 referral centers in Germany . INTERVENTION Patients were r and omized to an oral anticoagulation self-management group based on a structured treatment and teaching program and international normalized ratio ( INR ) self-monitoring . The control group received conventional care as provided by family physicians , including referral to specialists if necessary . MAIN OUTCOME MEASURES Deviation of INR values from the individual INR target range ( squared ) and the 5 categories of treatment-related quality of life . RESULTS Deviation of INR value from the mean of the INR target range was significantly lower in the intervention group at 3-month ( squared INR deviation , 0.59 vs 0.95 ; P<.001 ) and 6-month follow-up ( 0.65 vs 0.83 ; P=.03 ) compared with the control group . Also , the intervention group had INR values within the target range more often ( repeated measurement analysis for categorical data , P=.006 ) . The results were mainly due to less frequent suboptimal INR values in the intervention group ( 32.8 % vs 50.0 % [ P=.03 ] at 3-month , and 33.7 % vs 48.2 % [ P=.08 ] at 6-month follow-up ) . Treatment-related quality -of-life measures , especially treatment satisfaction scores , were significantly higher in the intervention group compared with controls . CONCLUSIONS An anticoagulation education program that includes self-management of anticoagulation therapy results in improved accuracy of anticoagulation control and in treatment-related quality -of-life measures . Further studies are needed to describe whether the program will reduce risk of bleeding or thromboembolism AIMS In Belgium , general practitioners ( GPs ) mainly manage oral anticoagulation therapy . To improve the quality of oral anticoagulation management by GPs and to compare different models and interventions , a r and omized clinical trial was performed . METHODS AND RESULTS Stratified r and omization divided 66 GP- practice s into four groups . A 6-month retrospective analysis assessed the baseline quality . In the prospect i ve study , each group received education on oral anticoagulation , anticoagulation files , and patient information booklets ( groups A , B , C , and D ) . Group B additionally received feedback every 2 months on their anticoagulation performance ; group C determined the international normalized ratio ( INR ) with a CoaguChek device in the doctor 's office or at the patient 's home ; and group D received Dawn AC computer assisted advice for adapting oral anticoagulation . For the different groups , the time spent in target INR range ( Rosendaal 's method ) and adverse events related to anticoagulation were determined and compared with the same quality indicators at baseline . There was a significant increase in per cent of time within 0.5 INR from target , from 49.5 % at baseline to 60 % after implementing the different interventions . However , neither the per cent in target range nor the event rates differed among the four groups . CONCLUSION The interventions significantly improved the quality of management of oral anticoagulation by Belgian GPs , mainly as a result of an education and support programme Background : The increase in numbers of patients receiving warfarin treatment has led to the development of alternative models of service delivery for oral anticoagulant monitoring . Patient self management for oral anticoagulation is a model new to the UK . This r and omised trial was the first to compare routine primary care management of oral anticoagulation with patient self management . Aim : To test whether patient self management is as safe , in terms of clinical effectiveness , as primary care management within the UK , as assessed by therapeutic international normalised ratio ( INR ) control . Method : Patients receiving warfarin from six general practice s who satisfied study entry criteria were eligible to enter the study . Eligible patients were r and omised to either intervention ( patient self management ) or control ( routine primary care management ) for six months . The intervention comprised two training sessions of one to two hours duration . Patients were allowed to undertake patient self management on successful completion of training . INR testing was undertaken using a Coaguchek device and regular internal/external quality control tests were performed . Patients were advised to perform INR tests every two weeks , or weekly if a dose adjustment was made . Dosage adjustment was undertaken using a simple dosing algorithm . Results : Seventy eight of 206 ( 38 % ) patients were eligible for inclusion and , of these , 35 ( 45 % ) declined involvement or withdrew from the study . Altogether , 23 intervention and 26 control patients entered the study . There were no significant differences in INR control ( per cent time in range : intervention , 74 % ; control , 77 % ) . There were no serious adverse events in the intervention group , with one fatal retroperitoneal haemorrhage in the control group . Costs of patient self management were significantly greater than for routine care ( £ 90 v £ 425/patient/year ) . Conclusion : These are the first UK data to demonstrate that patient self management is as safe as primary care management for a selected population . Further studies are needed to eluci date whether this model of care is suitable for a larger population BACKGROUND Vitamin K antagonist treatment is effective for prevention and treatment of thromboembolic events but frequent laboratory control and dose-adjustment are essential . Small portable devices have enabled patient self-monitoring of anticoagulation and self-adjustment of the dose . We compared this self-management of oral anticoagulant therapy with conventional management by a specialist anticoagulation clinic in a r and omised cross-over study . METHODS 50 patients on long-term oral anticoagulant treatment were included in a r and omised controlled crossover study . Patients were self-managed or were managed by the anticoagulation clinic for a period of 3 months . After this period the alternative strategy was followed for each patient . Prothrombin time ( expressed as international normalised ratio [ INR ] ) were measured at intervals of 1 - 2 weeks in both periods without knowledge of type of management . The primary endpoint was the number of measurements within the therapeutic range ( therapeutic target value + /-50.5 INR units ) . FINDINGS There was no significant difference in the overall quality of control of anticoagulation between the two study periods . Patients were for 55 % and for 49 % of the treatment period within a range of + /-0.5 from the therapeutic target INR during self-management and anticoagulation clinic management , respectively ( p=0.06 ) . The proportion of patients who spent most time in the therapeutic target range was larger during self-management than during anticoagulation clinic-guided management . The odds ratio for a better control of anticoagulation ( defined as the period of time in the therapeutic target range ) during self-management compared with anticoagulation clinic-guided management was 4.6 ( 95 % CI 2.1 - 10.2 ) . A patient-satisfaction assessment showed superiority of self-management over conventional care . INTERPRETATION Self-management of INR in the population in this study is feasible and appears to result in control of anticoagulation that is at least equivalent to management by a specialist anticoagulation clinic . It is also better appreciated by patients . Larger studies are required to assess the effect of this novel management strategy on the incidence of thromboembolic or bleeding complications BACKGROUND Self-management ( SM ) of warfarin by patients is an attractive strategy , particularly if it improves anticoagulation control and can be done safely under minimal physician supervision . OBJECTIVE To compare the effect of SM with physician-management ( PM ) on the maintenance of therapeutic anticoagulation . METHODS A r and omized , open-label eight-month trial was performed . Patients 18 years of age and older were eligible if they were receiving warfarin for at least one month before enrolment and required anticoagulation for at least one year to a target international normalized ratio ( INR ) of 2.0 to 3.0 or 2.5 to 3.5 . Exclusion criteria were a known hypercoaguable disorder , mental incompetence , a language barrier or an inability to attend training sessions . Patients r and omly assigned to SM tested their INR using a point-of-care device ( Pro Time Microcogulation System , International Technidyne Corporation , USA ) and adjusted their warfarin doses using a nomogram . Patients r and omly assigned to PM received usual care from their general practitioner . The primary outcome was to demonstrate 20 % improvement in anticoagulation control by SM . RESULTS One hundred forty patients were r and omly assigned ( 70 per group ) . Thirteen patients dropped out of SM early due to an inability to self-manage . Based on intention-to-treat analysis , there was no difference in the proportion of INR in range ( SM 64.8 % versus PM 58.7 % , P=0.23 ) or time in target range ( SM 71.8 % versus PM 63.2 % , P=0.14 ) . Patients managing their own therapy spent less time below the therapeutic range ( 15.0 % versus 27.3 % , P=0.04 ) . There were three major complications of thrombosis or bleeding , all occurring in the PM arm . All patients who completed SM preferred to continue with that strategy . CONCLUSIONS SM was not significantly better than PM in maintaining therapeutic anticoagulation . SM was feasible and appeared safe in the present study population Background Antithrombotic treatment is a continuous therapy that is often performed in general practice and requires careful safety management . The aim of this study is to investigate whether a best- practice model that applies major elements of case management and patient education , can improve antithrombotic management in primary healthcare in terms of reducing major thromboembolic and bleeding events . Methods This 24-month cluster-r and omized trial will be performed with 690 adult patients from 46 practice s. The trial intervention will be a complex intervention involving general practitioners , healthcare assistants , and patients with an indication for oral anticoagulation . To assess adherence to medication and symptoms in patients , as well as to detect complications early , healthcare assistants will be trained in case management and will use the Coagulation-Monitoring List ( Co-MoL ) to regularly monitor patients . Patients will receive information ( leaflets and a video ) , treatment monitoring via the Co-MoL and be motivated to perform self-management . Patients in the control group will continue to receive treatment as usual from their general practitioners . The primary endpoint is the combined endpoint of all thromboembolic events requiring hospitalization and all major bleeding complications . Secondary endpoints are mortality , hospitalization , strokes , major bleeding and thromboembolic complications , severe treatment interactions , the number of adverse events , quality of anticoagulation , health-related quality of life , and costs . Further secondary objectives will be investigated to explain the mechanism by which the intervention is effective : patients ’ assessment of chronic illness care , self-reported adherence to medication , general practitioners ’ and healthcare assistants ’ knowledge , and patients ’ knowledge and satisfaction with shared decision making . Practice recruitment is expected to take place between July and December 2012 . Recruitment of eligible patients will start in July 2012 . Assessment will occur at three time points : baseline and follow-up after 12 months and after 24 months . Discussion The efficacy and effectiveness of individual elements of the intervention , such as antithrombotic interventions , self-management concepts in orally anticoagulated patients , and the method ological tool of case management , have already been extensively demonstrated . This project foresees the combination of several proven instruments , as a result of which we expect to profit from a reduction in the major complications associated with antithrombotic treatment . Trial registration Current Controlled Trials IS RCT Background Self management of oral anticoagulation ( OAC ) decreases complication rates and improves quality of life . Manual and cognitive abilities of patients and patient training in a structured format are a precondition for this concept . Up to now , there is no evidence about knowledge increase from teaching programs . Methods Seventy-six patients ( mean age , 57.4 years , 71 % male ) who started long-term OAC were included in the prospect i ve multi-center study at three teaching centers representing different population s of anticoagulation patients : a department of cardiovascular surgery , an inpatient rehabilitation center and an anticoagulation clinic . The patients were trained in a structured education program for two days . For the evaluation , the patients performed st and ardized tests including 16 questions prior to start ( T0 ) , after each training unit ( T1/T2 ) and 6 weeks later ( T3 ) . The primary endpoint was the percentage of > 75 % of patients who could answer > 50 % of questions correctly at T3 . Secondary endpoints were the overall and item-specific percentages of correct answers at the end of each training unit ( T1 , T2 ) and at T3 . In addition , the teaching program was rated by the patients on a six-point rating scale . Results Seventy-four out of 76 patients gave at least 50 % correct answers at T3 ( 97.4 % ; 95 % confidence interval , 90.8–99.7 % ) . The average rates of correct answers developed from 40 % ( T0 ) , 86 % ( T1 ) , 94 % ( T2 ) to 96 % ( T3 ) . The greatest increase of knowledge was observed with blood components , interpretation of International Normalized Ratio ( INR ) value , and the interaction of anticoagulation with other variables ( e.g. drugs or infection ) . Patients rated the teaching program between 1 ( best rating ) and 2 at all time points . At T3 , the patients reported less fear of complications and less limitations in their daily life than in earlier evaluations . Conclusion The structured training program IN Ratio appears to be an appropriate instrument for instruction of INR self management . In comparison with baseline knowledge , the percentage of correctly answered questions was twice as high directly after the end of training and remained at a high level of > 90 % for at least 6 weeks BACKGROUND The use of warfarin reduces the rate of ischemic stroke in patients with atrial fibrillation but requires frequent monitoring and dose adjustment . Rivaroxaban , an oral factor Xa inhibitor , may provide more consistent and predictable anticoagulation than warfarin . METHODS In a double-blind trial , we r and omly assigned 14,264 patients with nonvalvular atrial fibrillation who were at increased risk for stroke to receive either rivaroxaban ( at a daily dose of 20 mg ) or dose-adjusted warfarin . The per- protocol , as-treated primary analysis was design ed to determine whether rivaroxaban was noninferior to warfarin for the primary end point of stroke or systemic embolism . RESULTS In the primary analysis , the primary end point occurred in 188 patients in the rivaroxaban group ( 1.7 % per year ) and in 241 in the warfarin group ( 2.2 % per year ) ( hazard ratio in the rivaroxaban group , 0.79 ; 95 % confidence interval [ CI ] , 0.66 to 0.96 ; P<0.001 for noninferiority ) . In the intention-to-treat analysis , the primary end point occurred in 269 patients in the rivaroxaban group ( 2.1 % per year ) and in 306 patients in the warfarin group ( 2.4 % per year ) ( hazard ratio , 0.88 ; 95 % CI , 0.74 to 1.03 ; P<0.001 for noninferiority ; P=0.12 for superiority ) . Major and nonmajor clinical ly relevant bleeding occurred in 1475 patients in the rivaroxaban group ( 14.9 % per year ) and in 1449 in the warfarin group ( 14.5 % per year ) ( hazard ratio , 1.03 ; 95 % CI , 0.96 to 1.11 ; P=0.44 ) , with significant reductions in intracranial hemorrhage ( 0.5 % vs. 0.7 % , P=0.02 ) and fatal bleeding ( 0.2 % vs. 0.5 % , P=0.003 ) in the rivaroxaban group . CONCLUSIONS In patients with atrial fibrillation , rivaroxaban was noninferior to warfarin for the prevention of stroke or systemic embolism . There was no significant between-group difference in the risk of major bleeding , although intracranial and fatal bleeding occurred less frequently in the rivaroxaban group . ( Funded by Johnson & Johnson and Bayer ; ROCKET AF Clinical Trials.gov number , NCT00403767 . ) BACKGROUND Increased frequency of prothrombin time testing , facilitated by patient self-testing ( PST ) of the International Normalized Ratio ( INR ) can improve the clinical outcomes of oral anticoagulation therapy ( OAT ) . However , oversight of this type of management is often difficult and time-consuming for healthcare professionals . This study reports the first r and omized controlled trial of an automated direct-to-patient expert system , enabling remote and effective management of patients on OAT . METHODS A prospect i ve , r and omized controlled cross-over study was performed to test the hypothesis that supervised PST using an internet-based , direct-to-patient expert system could provide improved anticoagulation control as compared with that provided by an anticoagulation management service ( AMS ) . During the 6 months of supervised PST , patients measured their INR at home using a portable meter and entered this result , along with other information , onto the internet web page . Patients received instant feedback from the system as to what dose to take and when the next test was due . During the routine care arm , patients attended the AMS at least every 4 - 6 weeks and were dosed by the anticoagulation pharmacist or physician . The primary outcome variable was the difference in the time in therapeutic range ( TTR ) between both arms . RESULTS One hundred and sixty-two patients were enrolled ( male 61.6 % , mean age 58.7 years ) , and 132 patients ( 81.5 % ) completed both arms . TTR was significantly higher during PST management than during AMS management ( median TTR 74 % vs 58.6 % ; z=5.67 , P < 0.001 ) . CONCLUSIONS The use of an internet-based , direct-to-patient expert system for the management of PST improves the control of OAT as compared with AMS management BACKGROUND Several studies have demonstrated that patient self-management of oral anticoagulant therapy ( OAT ) can improve treatment quality . However , most of these studies were not conducted within a specialized anticoagulation care system . The objective of the present study was to determine whether patient self-management of OAT improves the quality of care delivered by anticoagulation clinics . METHODS In this r and omized study by 2 Dutch anticoagulation clinics 341 patients aged between 18 and 75 years and receiving long-term OAT were divided into 4 groups : an existing routine care group of patients untrained in self-management ; a routine care group of trained patients ; a group managed weekly at an anticoagulation clinic where international normalized ratios were measured by trained patients ; and weekly patient self-management . A 2-step r and omization procedure was followed : first , a Zelen- design r and omization was performed to distribute patients ( without informing them ) to the existing care group or to receive training in self-management ; second , trained patients were r and omized to the 3 other study groups . RESULTS Only 25.6 % of invited patients agreed to participate in the training program . Patients who remained in the existing care group were within the international normalized ratio target range 63.5 % of the time . The type of coumarin taken was a major predicting factor of OAT quality . In all study groups phenprocoumon outperformed acenocoumarol by 11.6 % ( 95 % confidence interval [ CI ] , 6.6%-16.5 % ) . Weekly management with phenprocoumon led to a 6.5 % improvement ( 95 % CI , 0.0%-13.1 % ) in time in the international normalized ratio target range when patients were managed at an anticoagulation clinic and to an 8.7 % improvement ( 95 % CI , 1.6%-15.9 % ) when patients were self-managed . Weekly management with acenocoumarol did not improve the quality of OAT . CONCLUSION With selected patients , the quality of OAT obtained through patient self-management is at least as high as that delivered by specialized physicians at anticoagulation clinics . Weekly management of OAT with long-acting phenprocoumon has to be preferred at anticoagulation clinics or , where possible , through patient self-management Several studies suggest that patient self‐management ( PSM ) may improve the quality of oral anticoagulation therapy as measured by time spent within the international normalised ratio ( INR ) target range . We performed a prospect i ve r and omised control trial to determine whether the improvement in quality of treatment afforded by PSM is greater than that achieved by patient self‐testing ( PST ) alone . A total of 104 of 800 eligible patients aged 22–88 years ( median = 59·8 ) , attending our hospital anticoagulant clinic and receiving long‐term warfarin for > 8 months agreed to participate . Patients were r and omised to PSM ( n = 55 ) or PST ( n = 49 ) . Both groups measured their INR using the CoaguChek S every 2 weeks or more frequently if required , for a period of 6 months . Seventy‐seven of 104 ( 74 % ) patients completed the study ( PSM = 41 and PST = 36 ) . The ‘ drop out ’ rates for both groups were similar . There was no significant difference between the percentage time in target therapeutic range for PSM ( 69·9 % ) and PST ( 71·8 % ) . Both groups combined showed a significant improvement over the previous 6 months ( 71·0 % vs. 62·5 % ; P = 0·04 ) . Changes in time within the therapeutic range in individual patients ( + 5·86 ) also showed a significant difference . The quality of warfarin control in both PST and PSM may be superior to that achieved by conventional management in a specialised hospital anticoagulation clinic Severe thromboembolic and hemorrhagic complications following mechanical heart valve replacement essentially occur due to intense oral anticoagulation and fluctuating individual INR values around the target range . INR self-management can help to minimize these fluctuations . Beginning this therapeutic control immediately after mechanical heart valve replacement further reduces anticoagulant-induced complications . Included in the study were 1200 patients . The quality of oral anticoagulation also improved through INR self-management . Over an observation period of two years , nearly 80 % of INR values recorded by the patients themselves were within the target therapeutic range of 2.5 - 4.5 . This corresponds to a high significance of p < = 0.001 in favor of INR self-management . Only 64.9 % of INR values monitored by family practitioners were within the desired range . The results differed slightly in quality between patient groups with different levels of training ( comprehensive , secondary modern , grammar with or without university ) . Of patients trained in INR self-management following mechanical heart valve replacement , 91.7 % maintained their competence in this technique throughout the entire follow-up period . Only 8.3 % of those trained immediately after surgery were unable to continue with INR self-management Der Großteil der Patienten mit Vorhofflimmern ist durch ein thromboembolisches Ereignis gefährdet . Die Komplikationsrate kann durch eine effiziente Antikoagulation um zwei Drittel reduziert werden . Ob die Qualität der Therapieüberwachung durch das Selbstmanagement bei Patienten mit Vorhofflimmern ( SMAAF-Studie ) i m Vergleich zur herkömmlichen bei Hausarzt betreuten Patienten verbessert werden kann , war Gegenst and dieser prospektiven Multicenter- Studie . Bei Eignung zum Selbstmanagement sollten 2 000 Patienten in die beiden Studienarme r and omisiert werden . I m Untersuchungszeitraum von 12/99 bis 07/01 gaben lediglich 202 Patienten ( 64,3±9,2 Jahre , 69,3 % Männer ) ihr Einverständnis . Bei vorzeitigem Studienabbruch aufgrund zu niedriger Patientenzahl beschränkt sich der Gruppenvergleich auf die Auswertung gemessener INR-Werte mittels zweiseitigem t-Test . Von den 202 eingeschlossenen Patienten wurden 101 der Selbstmanagement-Gruppe ( 64,6±9,6 Jahre , 71,4 % Männer ) und 101 ( 64,1±8,9 Jahre , 61,4 % Männer , n.s . ) der Hausarztgruppe zugeordnet . Die Gesamtzahl der INR-Messungen betrug 2 865 , wobei 2 072 auf Patienten i m Selbstmanagement und 793 auf die Hausarztgruppe entfielen . Die Werte lagen bei Patienten i m Selbstmanagement mit 67,8 % i m Vergleich zur Hausarztgruppe mit 58,5 % signifikant häufiger ( p=0,0061 ) i m Zielbereich . Bezüglich der Verweildauer i m therapeutischen Bereich best and zwar ein Trend zugunsten der Selbstmanagement-Gruppe , jedoch kein signifikanter Unterschied ( 178,8±126 Tage vs. 155,9±118,4 Tage ) . In der Selbstmanagement- Gruppe traten zwei schwere Blutungen , in der Hausarztgruppe ein thromboembolisches Ereignis auf . Die Therapieüberwachung der oralen Antikoagulation durch das INR-Selbstmanagement ist bei Patienten mit Vorhofflimmern der Betreuung durch den Hausarzt nicht unterlegen . Most patients with atrial fibrillation are at risk of suffering thromboembolic events . This risk can be reduced by twothirds by efficient anticoagulation . This prospect i ve multi-center trial investigated whether the quality of treatment can be improved by self-management in patients with atrial fibrillations ( SMAAF Study ) compared to conventional patient management by the family doctor . Two thous and patients suitable for self-manage- ment were to be r and omized into the two arms of the study . In the period of investigation from December 1999 to July 2001 , only 202 patients ( 64.3±9.2 years , 69.3 % men ) consented to participate . The study was discontinued prematurely since the number of patients was too low . As a consequence , the group comparison is confined to the evaluation of the INR values measured using the two-tailed t test . Of the 202 patients included , 101 were assigned to the self-management group ( 64.6±9.6 years , 71.4 % men ) and 101 ( 64.1±8.9 years , 61.4 % men , n.s . ) were assigned to the group managed by the family doctor . The total number of INR measurements was 2 865 . This comprised 2 072 measurements in patients under self-management and 793 in the family doctor group . The values were within the target range significantly more frequently ( p=0.0061 ) in patients under self-management ( 67.8 % ) as compared to the family doctor group ( 58.5 % ) . There was a trend with regard to the time within target range , but the difference was not significant ( 178.8±126 days as compared to 155.9±118.4 days ) . In the self-management group , there were two severe hemorrhages , and there was one thromboembolic event in the family doctor group . Management of oral anticoagulation by INR self-management in patients with atrial fibrillation is not inferior to conventional care STUDY OBJECTIVE To evaluate the efficacy and accuracy of monitoring prothrombin times at home . DESIGN R and omized , prospect i ve cohort study . SETTING Out patients discharged from a university hospital or a community hospital . PATIENTS Fifty patients started on warfarin for the first time who demonstrated an ability to use the monitor and who had not achieved a stable response to warfarin in the hospital . INTERVENTION Oral anticoagulation therapy managed using a portable prothrombin time monitor compared with specialized anticoagulation clinic care . MEASUREMENTS AND MAIN RESULTS In the 46 patients who completed the 8-week study , the median percentage of time that patients in the home-monitor group ( n = 23 ) were within a range equal to the target prothrombin ratio + /- 0.3 , but always above 1.25 , was 93 % , compared with 75 % for patients in the clinic group ( n = 23 ) ( P = 0.003 ) . There was no significant difference between groups in the percentage of time above the therapeutic range ; however , the percentage of time that patients were subtherapeutic was significantly greater in the clinic group ( P less than 0.001 ) . There were no major thromboembolic or hemorrhagic complications in either group . Differences between home monitor measurements and corresponding clinical laboratory measurements using blood sample s drawn within 4 hours of the home test were comparable to differences observed between measurements using two different clinical laboratory instruments . CONCLUSIONS Use of a portable prothrombin time monitor by patients at home is feasible and provides accurate measurements . Patients doing home monitoring achieve superior anticoagulation control compared with those receiving st and ard anticoagulation clinic care BACKGROUND Effectiveness and safety of warfarin is associated with the time in therapeutic range ( TTR ) with an international normalised ratio ( INR ) of 2·0 - 3·0 . In the R and omised Evaluation of Long-term Anticoagulation Therapy ( RE-LY ) trial , dabigatran versus warfarin reduced both stroke and haemorrhage . We aim ed to investigate the primary and secondary outcomes of the RE-LY trial in relation to each centre 's mean TTR ( cTTR ) in the warfarin population . METHODS In the RE-LY trial , 18 113 patients at 951 sites were r and omly assigned to 110 mg or 150 mg dabigatran twice daily versus warfarin dose adjusted to INR 2·0 - 3·0 . Median follow-up was 2·0 years . For 18 024 patients at 906 sites , the cTTR was estimated by averaging TTR for individual warfarin-treated patients calculated by the Rosendaal method . We compared the outcomes of RE-LY across the three treatment groups within four groups defined by the quartiles of cTTR . RE-LY is registered with Clinical Trials.gov , number NCT00262600 . FINDINGS The quartiles of cTTR for patients in the warfarin group were : less than 57·1 % , 57·1 - 65·5 % , 65·5 - 72·6 % , and greater than 72·6 % . There were no significant interactions between cTTR and prevention of stroke and systemic embolism with either 110 mg dabigatran ( interaction p=0·89 ) or 150 mg dabigatran ( interaction p=0·20 ) versus warfarin . Neither were any significant interactions recorded with cTTR with regards to intracranial bleeding with 110 mg dabigatran ( interaction p=0·71 ) or 150 mg dabigatran ( interaction p=0·89 ) versus warfarin . There was a significant interaction between cTTR and major bleeding when comparing 150 mg dabigatran with warfarin ( interaction p=0·03 ) , with less bleeding events at lower cTTR but similar events at higher cTTR , whereas rates of major bleeding were lower with 110 mg dabigatran than with warfarin irrespective of cTTR . There were significant interactions between cTTR and effects of both 110 mg and 150 mg dabigatran versus warfarin on the composite of all cardiovascular events ( interaction p=0·036 and p=0·0006 , respectively ) and total mortality ( interaction p=0·066 and p=0·052 , respectively ) with reduced event rates at low cTTR , and similar rates at high cTTR . INTERPRETATION The benefits of 150 mg dabigatran at reducing stroke , 110 mg dabigatran at reducing bleeding , and both doses at reducing intracranial bleeding versus warfarin were consistent irrespective of centres ' quality of INR control . For all vascular events , non-haemorrhagic events , and mortality , advantages of dabigatran were greater at sites with poor INR control than at those with good INR control . Overall , these results show that local st and ards of care affect the benefits of use of new treatment alternatives . FUNDING Boehringer Ingelheim Context Although many out patients require oral anticoagulation , the optimal management of outpatient anticoagulation remains uncertain . Studies have demonstrated the feasibility of patient self-management using portable coagulometers , but the studies that compared patient outcomes with self-management and those with conventional management in an anticoagulation clinic did not find a better outcome with self-management . Contribution In this r and omized , controlled trial of 737 patients , patients assigned to self-management of anticoagulation achieved a similar level of control and had fewer adverse events than patients assigned to conventional management . Implication s Health care providers should begin to implement patient self-management of oral anticoagulation with portable coagulometers in mainstream practice . The Editors Indications for oral anticoagulant treatment to prevent thromboembolic disease have increased in recent years ( 1 ) . Prothrombin times must be monitored frequently in patients taking oral anticoagulants to determine the safest dose and to minimize the risk for complications . The clinical management of oral anticoagulant treatment improved greatly after the international normalized ratio ( INR ) was introduced as a measurement of anticoagulation intensity ( 1 ) . The establishment of accurate therapeutic INR ranges was also beneficial . Target ranges include the safest INR values that carry the lowest risk for hemorrhagic or thromboembolic complications ( 2 ) . Despite these improvements , however , serious complications are still associated with oral anticoagulant treatment ( 3 , 4 ) , and management by specialized staff at anticoagulation clinics seems to be safer than other clinical strategies in terms of numbers of complications ( 5 - 7 ) . Currently , portable coagulometers are available for determining INR easily and reliably ( 8) . This technology provides interesting clinical models for the control of oral anticoagulant treatment , the most promising of which are patient self-testing and patient self-management . For patient self-testing , patients measure INRs themselves and ask their referring physicians for the proper anticoagulant dose . Patient self-management assumes that patients will adjust their own doses and is the most autonomous strategy . Several published studies have compared these strategies with usual care ( that is , monitoring of oral anticoagulant treatment by practitioners ) ( 9 - 13 ) or with specialized anticoagulation clinics ( 14 - 18 ) . Although these studies showed that both patient self-testing and patient self-management are feasible , their sample s were relatively small ( 9 , 11 , 13 , 14 - 18 ) or included selected patients with mechanical valve prostheses ( 10 ) or patients older than 65 years of age ( 12 ) . In general , previous studies indicate that patient self-management may be superior to management by general practitioners or anticoagulation clinics in quality of INR control ( 10 - 18 ) . In addition , Krtke and Krfer ( 10 ) , Beyth and associates ( 12 ) , and Sawicki ( 13 ) reported a decrease in major complications among self-managed patients compared with patients managed by general practitioners . To date , no published data have suggested a better clinical outcome ( decrease in associated complications ) with patient self-management than with specialized management at an anticoagulation clinic ( 5 , 19 ) . We performed a r and omized , controlled trial to directly compare self-management of oral anticoagulant treatment , as evaluated in terms of efficacy and safety in unselected patients , with management in an anticoagulation clinic . Methods Study Design The Alternative Control of Oral Anticoagulant Treatment ( ACOA ) trial is a single-center , central ly r and omized , controlled study that was performed at Hospital de la Santa Creu i Sant Pau , Barcelona , Spain , from January 2001 to July 2002 . The hematologists who manage our anticoagulation clinic use a homogeneous dosing protocol and st and ard protocol s to manage situations that increase clinical risk . The clinical staff includes trained nurses . Computers control the clinical data and INR records , ensuring excellent follow-up . Patients and their relatives receive basic education at the beginning of oral anticoagulant treatment , including information on the main characteristics of oral anticoagulants , potential risks , rationale for periodic monitoring , and drug interactions . Samsa and Matchar ( 20 ) recommended that these characteristics be used to provide an appropriate control group in a trial on patient self-management . The institutional review board of our hospital approved the study . Recruitment Phase The recruitment phase began with computerized r and om selection of 1500 patients from the more than 5000 who were receiving oral anticoagulant treatment controlled in our hospital . We included any ambulatory patient 18 years of age or older who had been receiving long-term anticoagulant therapy for at least 3 months before entering the study . We excluded patients who were younger than 18 years of age , who had a severe physical or mental illness without a responsible caregiver , or who were of foreign origin and were unable to underst and Spanish . Once the patient ( or his or her caregiver ) agreed to participate , written informed consent was obtained . Next , central ized telephone r and omization assigned the patient to the experimental group ( patient self-management ) or to the control group ( conventional management ) . The allocation sequence was generated at the hospital 's epidemiology department , and the sequence of r and omization was concealed until the patient was assigned to a group . To facilitate comparability between study groups , this r and omization was stratified according to sex , age ( 70 years of age or < 70 years of age ) , and indication for oral anticoagulant treatment ( 4 groups ) . Members of our anticoagulation clinic enrolled participants and assigned them to groups . Baseline data included demographic details , clinical information on associated risk factors , other medications , previous length of anticoagulant therapy , bleeding or thromboembolic complications during oral anticoagulant treatment , and target INR range . Follow-up for patients assigned to the conventional management group was done immediately . Patients in the self-management group received a training course first , and follow-up was not performed until the nurse teaching the course judged that the patients had acquired a minimum of expertise in self-management . Training Course An educational program was design ed to optimize the number of patients able to underst and and safely perform self-management ( Appendix ) . It was similar to the German program developed by Sawicki ( 13 ) but was demographically adapted to the characteristics of the Spanish population , considering differences in daily schedules , diet , educational level , and other idiosyncratic factors . The program consisted of 2 sessions of 2 hours each on consecutive days . A specially trained nurse was responsible for teaching the patients in small , organized groups . The lessons included basic theoretical and practical concepts involving the use of a coagulometer , interpretation of INR , and adjustment of dose . The concepts of target range and dose modification were emphasized when necessary . A simple card system was design ed to help the patient select the correct dose . For each target range , a specific card was provided . Patients were taught to use the portable coagulometer CoaguChek S ( Roche Diagnostics , Mannheim , Germany ) with the appropriate reagent strips . Follow-up Phase Normally , the patients in the conventional management group visited our hospital every 4 weeks to check their INRs . When the INR result was out of target range , our dosing protocol indicated that we should advance the next appointment for INR testing to 1 or 2 weeks . International normalized ratio was determined by means of a st and ard KC 10 coagulometer ( Amelung , Lemgo , Germany ) . As a thromboplastin , we used Thromborel S ( Behring , Marburg , Germany ) . A hematologist experienced in oral anticoagulation management adjusted the dose and made the appointment for the next INR test . Patients in the self-management group performed the INR tests at home once per week using the CoaguChek S kit . They determined the appropriate dose of oral anticoagulant and the time of the next INR test . All of the INR results in both groups were entered into a computer ( in the central system of our anticoagulation clinic or in the portable coagulometers ) to facilitate data management . Patients in both groups were interviewed monthly by telephone to record any complications or changes in their health status . For the conventional management group , these interviews were done approximately midway between hospital visits . The questions addressed minor or major bleeding , thromboembolic events , episodic diseases , changes in long-term medications , and hospital stays . Associated complications were diagnosed and evaluated by a third physician who was not involved in the trial and was unaware of patients ' study group . St and ard criteria were used to diagnose any thromboembolic complications . Transient ischemic attack was diagnosed clinical ly by a neurologist , and superficial thrombophlebitis was diagnosed clinical ly by an angiologist . To diagnose stroke , arterial embolism , venous thromboembolism , pulmonary embolism , or valve thrombosis , we used widely accepted methods ( computed tomography or magnetic nuclear resonance imaging , angiography , surgical diagnosis , Doppler ultrasonography , phlebography , lung angiography or ventilation-perfusion lung scanning , cardiac ultrasonography , or fluoroscopy ) . All thromboembolic complications were considered major events . Life-threatening bleeding or bleeding requiring transfusion or hospital admission was considered a major event . Any other bleeding was considered a minor event . Statistical Analysis Study outcomes were evaluated on an intention-to-treat basis and also on an on-treatment basis . UNLABELLED SUBJECT OF THE EVIDENCE -BASED ANALYSIS : The purpose of this evidence based analysis report is to examine the safety and effectiveness of point-of-care ( POC ) international normalized ratio ( INR ) monitoring devices for patients on long-term oral anticoagulation therapy ( OAT ) . CLINICAL NEED TARGET POPULATION AND CONDITION Long-term OAT is typically required by patients with mechanical heart valves , chronic atrial fibrillation , venous thromboembolism , myocardial infa rct ion , stroke , and /or peripheral arterial occlusion . It is estimated that approximately 1 % of the population receives anticoagulation treatment and , by applying this value to Ontario , there are an estimated 132,000 patients on OAT in the province , a figure that is expected to increase with the aging population . Patients on OAT are regularly monitored and their medications adjusted to ensure that their INR scores remain in the therapeutic range . This can be challenging due to the narrow therapeutic window of warfarin and variation in individual responses . Optimal INR scores depend on the underlying indication for treatment and patient level characteristics , but for most patients the therapeutic range is an INR score of between 2.0 and 3.0 . The current st and ard of care in Ontario for patients on long-term OAT is laboratory-based INR determination with management carried out by primary care physicians or anticoagulation clinics ( ACCs ) . Patients also regularly visit a hospital or community-based facility to provide a venous blood sample s ( venipuncture ) that are then sent to a laboratory for INR analysis . Experts , however , have commented that there may be under-utilization of OAT due to patient factors , physician factors , or regional practice variations and that sub-optimal patient management may also occur . There is currently no population -based Ontario data to permit the assessment of patient care , but recent systematic review s have estimated that less that 50 % of patients receive OAT on a routine basis and that patients are in the therapeutic range only 64 % of the time . OVERVIEW OF POC INR DEVICES POC INR devices offer an alternative to laboratory-based testing and venipuncture , enabling INR determination from a fingerstick sample of whole blood . Independent evaluations have shown POC devices to have an acceptable level of precision . They permit INR results to be determined immediately , allowing for more rapid medication adjustments . POC devices can be used in a variety of setting s including physician offices , ACCs , long-term care facilities , pharmacies , or by the patients themselves through self-testing ( PST ) or self-management ( PSM ) techniques . With PST , patients measure their INR values and then contact their physician for instructions on dose adjustment , whereas with PSM , patients adjust the medication themselves based on pre-set algorithms . These models are not suitable for all patients and require the identification and education of suitable c and i date s. Potential advantages of POC devices include improved convenience to patients , better treatment compliance and satisfaction , more frequent monitoring and fewer thromboembolic and hemorrhagic complications . Potential disadvantages of the device include the tendency to underestimate high INR values and overestimate low INR values , low thromboplastin sensitivity , inability to calculate a mean normal PT , and errors in INR determination in patients with antiphospholipid antibodies with certain instruments . Although treatment satisfaction and quality of life ( QoL ) may improve with POC INR monitoring , some patients may experience increased anxiety or preoccupation with their disease with these strategies . EVIDENCE -BASED ANALYSIS METHODS RESEARCH QUESTIONS 1 . EffectivenessDoes POC INR monitoring improve clinical outcomes in various setting s compared to st and ard laboratory-based testing?Does POC INR monitoring impact patient satisfaction , QoL , compliance , acceptability , convenience compared to st and ard laboratory-based INR determination ? Setting s include primary care setting s with use of POC INR devices by general practitioners or nurses , ACCs , pharmacies , long-term care homes , and use by the patient either for PST or PSM . 2 . Cost-effectivenessWhat is the cost-effectiveness of POC INR monitoring devices in various setting s compared to st and ard laboratory-based INR determination ? INCLUSION CRITERIA English- language RCTs , systematic review s , and meta-analysesPUBLICATION DATE S : 1996 to November 25 , 2008 POPULATION : patients on OATINTERVENTION : anticoagulation monitoring by POC INR device in any setting including anticoagulation clinic , primary care ( general practitioner or nurse ) , pharmacy , long-term care facility , PST , PSM or any other POC INR strategy MINIMUM SAMPLE SIZE : 50 patients Minimum follow-up period : 3 monthsCOMPARATOR : usual care defined as venipuncture blood draw for an INR laboratory test and management provided by an ACC or individual practitioner OUTCOMES Hemorrhagic events , thromboembolic events , all-cause mortality , anticoagulation control as assessed by proportion of time or values in the therapeutic range , patient reported outcomes including satisfaction , QoL , compliance , acceptability , convenience EXCLUSION CRITERIA Non- RCTs , before-after studies , quasi-experimental studies , observational studies , case reports , case series , editorials , letters , non- systematic review s , conference proceedings , abstract s , non-English articles , duplicate publications Studies where POC INR devices were compared to laboratory testing to assess test accuracy Studies where the POC INR results were not used to guide patient management METHOD OF REVIEW A search of electronic data bases ( OVID MEDLINE , MEDLINE In-Process & Other Non-Indexed Citations , EMBASE , The Cochrane Library , and the International Agency for Health Technology Assessment [ INAHTA ] data base ) was undertaken to identify evidence published from January 1 , 1998 to November 25 , 2008 . Studies meeting the inclusion criteria were selected from the search results . Reference lists of selected articles were also checked for relevant studies . SUMMARY OF FINDINGS Five existing review s and 22 articles describing 17 unique RCTs met the inclusion criteria . Three RCTs examined POC INR monitoring devices with PST strategies , 11 RCTs examined PSM strategies , one RCT included both PST and PSM strategies and two RCTs examined the use of POC INR monitoring devices by health care professionals . ANTICOAGULATION CONTROL Anticoagulation control is measured by the percentage of time INR is within the therapeutic range or by the percentage of INR values in the therapeutic range . Due to the differing method ologies and reporting structures used , it was deemed inappropriate to combine the data and estimate whether the difference between groups would be significant . Instead , the results of individual studies were weighted by the number of person-years of observation and then pooled to calculate a summary measure . Across most studies , patients in the intervention groups tended to have a higher percentage of time and values in the therapeutic target range in comparison to control patients . When the percentage of time in the therapeutic range was pooled across studies and weighted by the number of person-years of observation , the difference between the intervention and control groups was 4.2 % for PSM , 7.2 % for PST and 6.1 % for POC use by health care practitioners . Overall , intervention patients were in the target range 69 % of the time and control patients were in the therapeutic target range 64 % of the time leading to an overall difference between groups of roughly 5 % . MAJOR COMPLICATIONS AND DEATHS There was no statistically significant difference in the number of major hemorrhagic events between patients managed with POC INR monitoring devices and patients managed with st and ard laboratory testing ( OR = 0.74 ; 95 % CI : 0.52- 1.04 ) . This difference was non-significant for all POC strategies ( PSM , PST , health care practitioner ) . Patients managed with POC INR monitoring devices had significantly fewer thromboembolic events than usual care patients ( OR = 0.52 ; 95 % CI : 0.37 - 0.74 ) . When divided by POC strategy , PSM result ed in significantly fewer thromboembolic events than usual care ( OR = 0.46 . ; 95 % CI : 0.29 - 0.72 ) . The observed difference in thromboembolic events for PSM remained significant when the analysis was limited to major thromboembolic events ( OR = 0.40 ; 95 % CI : 0.17 - 0.93 ) , but was non-significant when the analysis was limited to minor thromboembolic events ( OR = 0.73 ; 95 % CI : 0.08 - 7.01 ) . PST and GP/Nurse strategies did not result in significant differences in thromboembolic events , however there were only a limited number of studies examining these interventions . No statistically significant difference was observed in the number of deaths between POC intervention and usual care control groups ( OR = 0.67 ; 95 % CI : 0.41 - 1.10 ) . This difference was non-significant for all POC strategies . Only one study reported on survival with 10-year survival rate of 76.1 % in the usual care control group compared to 84.5 % in the PSM group ( P=0.05 ) . ES Table 1 : Summary Results of Meta-Analyses of Major Complications and Deaths in POC INR Monitoring Studies EventNo . of trials ( patients ) OR(M-H , R and om Effects)95 % CIMajor Haemorrhages16 (5057)0.740.52 to 1.04Thromboembolic events16 (5057)0.520.37 to 0.74Deaths11 (2906)0.670.41 to 1.10 PATIENT SATISFACTION AND QUALITY OF LIFE : Quality of life measures were reported in eight studies comparing POC INR monitoring to st and ard laboratory testing using a variety of measurement tools . It was thus not possible to calculate a quantitative summary measure . The majority of studies reported favourable impacts of POC INR monitoring on QoL and found better treatment satisfaction with POC monitoring . Results from a pre- analysis patient and caregiver focus group conducted in Ontario also indicated improved patient QoL with POC monitoring . ( BACKGROUND The efficacy of self-managed oral anticoagulant therapy has been addressed in few r and omized , controlled trials , which have provided inconsistent results . The aim of this study was to compare the quality of self-managed oral anticoagulant therapy with conventional management . METHODS This was a pragmatic , open-label , r and omized , controlled trial where 100 patients receiving long-term oral anticoagulant therapy referred to a Danish clinic for self-management was r and omized to either self-management of oral anticoagulant therapy ( including a teaching program of self-management followed by 6 months of self-management ) or 6 months of conventional management . The primary endpoint was an intention-to-treat analysis of a composite score combining the variance ( median square of the st and ard deviation ) of the International Normalized Ratio ( INR ) value ( using a blinded control sample analyzed monthly by a reference laboratory ) , death , major complications , or discontinuation from the study . Secondary endpoints - assessed in per- protocol analyses - were the variance of the INR value ( using the blinded control sample ) and time within therapeutic INR target range using the st and ard INR values from the coagulometer and laboratory measurement . RESULTS There was no significant difference in the primary endpoint between the self-management and conventional management groups ( composite score 0.16 vs. 0.24 , respectively , p=0.09 ) . Self-management was significantly better ( 0.16 vs. 0.24 , p=0.003 ) with regard to the variance in a per- protocol analysis . The difference in time within therapeutic INR target range was not significantly better ( 78.7 % vs. 68.9 % , p=0.14 ) using self-management . CONCLUSION The quality of self-management of oral anticoagulant therapy is at least as good as that provided by conventional management Of 125 patients aged 65 years or over , with atrial fibrillation taking warfarin for at least 12 months , with a st and ard deviation ( SD ) of prothrombin time , expressed as the International Normalized Ratio ( INR ) > 0·5 over the previous 6 months , 40 were r and omized to continue with usual clinic care and 85 to receive education about warfarin . Of these , 44 were r and omized to self‐monitor their INR and 41 returned to clinic . Compared with the previous 6 months there was a significant increase in percentage time within the therapeutic range for the 6 months following education [ 61·1 vs. 70·4 ; mean difference 8·8 ; 95 % confidence interval ( CI ) : −0·2–17·8 ; P = 0·054 ] and following education and self‐monitoring ( 57 vs. 71·1 ; mean difference 14·1 ; 95 % CI : 6·7–21·5 ; P < 0·001 ) , compared with those patients following usual clinic care ( 60·0 vs. 63·2 ; mean difference 3·2 ; 95 % CI : −7·3–13·7 ) . Using the same comparative periods , the INR SD fell by 0·24 ( P < 0·0001 ) in the group allocated to education and self‐monitoring , 0·26 ( P < 0·0001 ) in the group receiving education alone and 0·16 ( P = 0·003 ) in the control group . Inter‐group differences were not statistically significant ( intervention groups 0·26 ± 0·30 vs. control 0·16 ± 0·3 , P = 0·10 ) . Quality ‐of‐life measurements and health beliefs about warfarin were unchanged ( apart from emotional role limitation ) with education or education and self‐monitoring . Patient education regarding anticoagulation therapy could be a cost‐effective initiative and is worthy of further study BACKGROUND This study was conducted to assess the ability of patients receiving heart valve replacements to practice self-managed anticoagulation using a portable coagulometer . METHODS We carried out a prospect i ve , r and omized trial , comparing self-managed anticoagulation with conventional management . Patients practicing self-managed anticoagulation ( 51 patients ) did so at home , measuring their international normalized ratio and then deciding on their dosage of warfarin , while conventionally controlled patients ( n = 49 ) attended hospital clinics or were managed by their family physicians . RESULTS We successfully trained 41 of 44 patients who agreed to self-manage their anticoagulant therapy ; 34 of the 41 managed their own anticoagulation at home for 2 years . Their control , assessed by a number of tests in range ( 67.6 % versus 58.0 % ) and time in therapeutic range ( 76.5 % versus 63.8 % ) , was significantly better than that for the group managed conventionally ( p < 0.0001 ) . There was no significant difference in mortality or morbidity between the two groups . CONCLUSIONS Self-managed anticoagulation is a reliable , easily learned method of controlling anticoagulation , and it is suitable for approximately two thirds of patients , with excellent results Bleeding is the major side effect of warfarin and is a major deterrent to its use , especially in older patients . Older people are widely thought to be at increased risk for warfarin-related bleeding ( 1 - 8 ) , and they are less likely to be treated with warfarin , even when it has been proven efficacious , in part because of concern about risk for bleeding ( 9 - 13 ) . Efforts that reduce the frequency of major warfarin-related bleeding not only will increase the net benefit of therapy but also will facilitate more appropriate and widespread use of warfarin therapy in older patients . Methods for identifying patients at highest risk for bleeding have recently advanced ( 5 - 7 , 14 - 21 ) , and experience with specialized programs that coordinate the management of anticoagulant therapy suggests that clinical outcomes may be improved ( 6 , 14 , 18 , 22 - 27 ) . However , there is little controlled or experimental evidence on how to optimize management of anticoagulant therapy in older patients and prevent bleeding . We developed a multicomponent comprehensive program for management of warfarin therapy aim ed at improving control of the anticoagulant effect and reducing events ( such as use of an interacting medicine ) that might precipitate bleeding . We hypothesized that this intervention would be acceptable to most elderly persons starting warfarin therapy and would reduce the frequency of warfarin-related major bleeding . Methods Patients Patients hospitalized at University Hospitals of Clevel and , a 900-bed teaching hospital , between September 1992 and October 1995 who were 65 years of age or older and were receiving 10 000 units or more of intravenous unfractionated heparin every 24 hours were screened daily . Of these patients , we identified 426 persons who were 65 years of age or older , who resided in Cuyahoga County , Ohio , and for whom treatment with warfarin was planned for 10 or more days ( Figure 1 ) . Patients were excluded if they had been treated with warfarin at any time during the previous 6 months , were admitted from a nursing home , were enrolled in another clinical trial , were too ill to give consent and had no available surrogate , were discharged prematurely , or did not speak English ; if their private physician refused to participate ; or if no r and om allocation was taking place ( for example , during vacations or holidays ) . Eligible patients who were enrolled did not differ significantly from those who were not enrolled with regard to age , ethnicity , sex , or indication for therapy . Figure 1 . Eligibility and r and om assignment of patients . Patients were stratified according to their baseline risk for major bleeding by using the Outpatient Bleeding Risk Index ( 20 ) . This index includes four independent risk factors for major bleeding : age 65 years or older , history of gastrointestinal bleeding , history of stroke , and one or more of four specific comorbid conditions ( recent myocardial infa rct ion , hematocrit<30 % , creatinine concentration>133 mol/L [ 1.5 mg/dL ] , or diabetes mellitus ) . Patients with one or two risk factors were classified as intermediate risk , and those with three or more risk factors were classified as high risk ; estimated frequencies of major bleeding in 6 months were 6 % and 35 % , respectively . After stratification , patients were r and omly assigned to receive usual care or intervention . Informed consent for observation and data collection was then sought from both groups , and informed consent to participate in the intervention was sought from the intervention group . This method , initially proposed by Zelen ( 28 ) , allows the study to test the effectiveness of offering the intervention rather than simply the efficacy of the intervention in patients who consent to participation before r and om assignment . The sample size was calculated to provide 80 % power and an level of 0.05 . The study protocol and informed consent procedures were approved by the hospital 's institutional review board . Intervention The intervention had two main components . The first component consisted of a guideline -based consultation that assessed the patient 's indications for therapy and potential risk factors for warfarin-related bleeding . We used this method previously to reduce the frequency of anticoagulant-related bleeding during hospitalization ( 27 ) . Specific recommendations about modifiable risk factors , such as use of nonsteroidal anti-inflammatory drugs , were made and implemented . The study investigators directed warfarin dosing and international normalized ratio ( INR ) testing after hospital discharge . The second component included patient education , coaching , and self-monitoring of prothrombin time ; this component was grounded in social learning theory ( 29 - 31 ) and experimental evidence ( 32 , 33 ) showing that increasing participation of patients in their care can improve clinical outcomes but that increasing patient knowledge alone is insufficient ( 34 , 35 ) . Patient education consisted of one-on-one teaching by a lay educator using a specifically formatted workbook for older adults to teach them about warfarin , indications for its use , drug and food interactions , and the signs and symptoms of bleeding . The lay educator review ed the workbook and was taught how to use the prothrombin time monitor by one of the authors but had no formal medical training . Coaching was aim ed to increase patients ' participation in their care and to improve information-seeking skills . Patients were trained and encouraged to communicate more effectively with physicians and other health personnel about a range of issues , such as health concerns , drug interactions , or changes in lifestyle or diet . Finally , patients were taught to self-monitor the prothrombin time by using a home portable monitor ( Coumatrak Protime Test System , Biotrack , Inc. , Mountain View , California ) . The monitor uses a fingerstick to obtain a blood sample and has well-established accuracy ( 36 - 38 ) . Patients were initially assessed , educated , and taught to use the portable monitor while hospitalized ; training lasted 30 minutes to 1 hour . They were seen daily while hospitalized , warfarin therapy was adjusted as needed , and any concerns or questions about anticoagulant therapy were addressed . Within 3 days of discharge from the hospital , the lay educator or study investigator made a home visit to assess patients ' use of the portable monitor and to check the prothrombin time . In general , patients were instructed to check their prothrombin time three times during the first week after hospital discharge , weekly for the remainder of the first month , and monthly thereafter depending on their results . Patients phoned in their results to the coach , who review ed the results with one of the investigators and provided same-day follow-up , including recommendations for dose and subsequent INR testing . Patients were instructed to call whenever they had questions or concerns about their warfarin management or possible side effects , if they were hospitalized for any reason , or if they began receiving new medications . After the 6-month intervention period , management and dosing of warfarin therapy reverted back to patients ' personal physicians . Patients assigned to usual care received medical care , including management , dosing , and medical information , according to the discretion and practice s of their personal physician . Data Collection Trained abstract ors who were not involved with the intervention component of the study collected data from the medical chart at the start of anticoagulant therapy ; at each subsequent hospitalization ; and by blinded interview at enrollment and 1 , 3 , and 6 months after enrollment and every 6 months thereafter . Data elements included demographic characteristics , clinical history including comorbid diagnoses , indications for therapy , potential risk factors for bleeding , functional status , and new illnesses or comorbid conditions that developed after enrollment . Surveillance for bleeding and thromboembolism was conducted identically in the intervention and control groups and consisted of 12 items inquiring about bleeding and thromboembolism at each follow-up interview . Whenever an event was reported , the clinical characteristics of the bleeding or thromboembolic episode were determined by review of the relevant medical record and abstract ed without identifying patient information onto a st and ard form . All date s of death were confirmed by death certificates , and all causes of death were confirmed by review of death certificates and medical records . Follow-up was complete for all patients . End Points The primary end point was the first major bleeding event during the 6-month intervention period . Using explicit criteria in the Bleeding Severity Index ( 39 ) for the amount , rate , and consequences of bleeding , we defined major bleeding as overt bleeding that led to the loss of at least 2.0 units of blood in 7 days or less or was otherwise life-threatening ( for example , intracranial bleeding ) . Bleeding was classified without information about possible risk factors or r and omization status . Two author- review ers who were blinded to group assignment adjudicated bleeding events ; their agreement was high ( statistic , 0.97 ) . Secondary outcomes were death and recurrent venous thromboembolism at 6 months ; major bleeding after 6 months ; and control of anticoagulant therapy during the first 6 months of therapy , as measured by the INR . The therapeutic range of the INR was defined as 2.5 to 3.5 for persons with mechanical heart valves and 2.0 to 3.0 for persons with all other indications ( 40 ) . Therapeutic quality control was assessed by using the patient-time approach , described by Rosendaal and colleagues ( 41 ) , for three time periods after discharge from the hospital : 0 to 1 month , 1 to 3 months , and 3 to 6 months of therapy . This approach estimates the amount of time a patient is in the therapeutic range based on the actual INRs measured , assuming a linear relationship between consecutive INRs . Patients with only one An ageing population and the continuing expansion of clinical indications for coumadin therapy have increased pressure on hospital anticoagulant clinics . One solution is patient self‐testing ( PST ) of the international normalized ratio ( INR ) using capillary blood sample s on point‐of‐care coagulation monitors at home . We conducted a prospect i ve study to determine whether patients can achieve accurate INR values through PST , using the CoaguChek S ( Roche Diagnostics , Lewes , UK ) . The main outcome measurements were : comparability of INR values obtained by PST and the hospital laboratory , patient acceptability as assessed by a question naire and anticoagulant control . Eighty‐four patients [ 53 men , 31 women ; median age 59 years ( range 26–83 ) ] , receiving long‐term oral anticoagulation ( warfarin ) , were recruited from our Anticoagulation Clinic . Patients were r and omized to weekly self‐testing or continuing 4‐weekly hospital laboratory monitoring of INR . Comparison of INRs ( n = 234 ) showed no significant differences between the CoaguChek ( median INR 3·02 ) and laboratory testing ( median INR 3·07 ) . There was excellent correlation between the two methods ( r = 0·95 ) , with 85 % of CoaguChek results within 0·5 INR units of the laboratory method . On four occasions , differences of > 1 unit INR were obtained , but in each case the patient 's anticoagulation was unstable ( INR > 4·5 by both methods ) and the differences in INR would not have altered patient management . 87 % of patients found self‐testing straightforward , 87 % were confident in the result they obtained and 77 % preferred self‐testing . We conclude that PST is a reliable alternative to hospital clinic attendance and is acceptable to the majority of suitably trained patients INTRODUCTION Thromboembolic accidents and haemorrhage are the main complications observed during long-term follow-up of mechanical heart valve patients . Several suggestions for improving anticoagulation quality have been made , including international normalised ratio ( INR ) self-monitoring . OBJECTIVES We report the preliminary results of a single-centre , open , r and omised study ( scheduled population of 200 patients ) , which compares monthly laboratory monitoring ( group A ) versus weekly self-monitoring of INR ( group B ) . The primary aim is INR stability improvement within the target range , and the secondary aim is adverse events reduction . PATIENTS AND METHODS Between May 2004 and June 2005 , 67 patients with an average age of 56.6 years ( + /-9.6 ) , were enrolled in the study ( group A : 34 patients , group B : 33 patients ) . The mean follow-up was 47 weeks ( + /-11.5 ) . The two groups differed only in the sex ratio ( 44.1 and 21.2 % of women in groups A and B respectively , p=0.0459 ) . Mechanical heart valves were aortic in 73 % of patients , mitral in 13.5 % , and multiple in 13.5 % . Sixty-five patients ( 97 % ) were treated with fluindione , the others with acenocoumarol . The intraclass correlation coefficient between the self- and laboratory-monitored INR was 0.75 . RESULTS The time spent in the INR target range ( group A : 53+/-19 % , group B : 57+/--19 % , p=0.45 ) and the time spent in the INR therapeutic range , between 2 and 4.5 , ( group A : 86+/-14 % , group B : 91+/-7 % , p=0.07 ) are longer in group B , but not significantly so . For patients outside the range , the absolute mean deviation of INR from the target or therapeutic range ( range st and ardized between 0 and 100 ) is lower for the self-monitoring group ( 41.1+/-39.3 and 11.27+/-11.2 ) than for the control group ( 62.4+/-72.6 and 39.2+/-52.8 ) . This difference is significant ( p=0.0004 and p=0.0005 ) . Eighteen adverse events were reported : 17 haemorrhages , 13 in group A ( 9 mild , 4 serious ) and four in group B ( all mild ) , and one sudden death in group B , two days after the patient 's discharge . No thromboembolic events were reported . Six patients ( 8.8 % ) , 3 in each group , dropped out of the study . CONCLUSION This first study evaluating INR self-monitoring in France shows that this method leads to better stability of the INR within the target range . On the basis of these preliminary data , this appears to be related to a decrease in serious haemorrhages ( 11.8 % serious haemorrhage cases in group A versus 0 % in group B , p=0.06 , NS ) Although many patients with long-term oral anticoagulation ( OAC ) can manage their medication safely and reliably themselves , no study on elderly patients has as yet assessed the safety and efficacy of OAC self-management with major thromboembolic and haemorrhagic complications as primary outcomes . In this multi-centre trial , patients aged 60 years or more were r and omised into a self-management ( SMG ) ( N = 99 ) or routine care group ( RCG ) ( N = 96 ) . The primary outcome was the combined endpoint of all thromboembolic events requiring hospitalisation and all major bleeding complications . Mean follow-up was 2.9 + /- 1.2 and 3.0 + /- 1.1 years in the SMG and RCG , respectively . In intention-to-treat analysis , 12 patients in the SMG versus 22 patients in the RCG reached a primary endpoint ( hazard ratio [ HR ] : 0.50 ; 95 % confidence interval [ CI ] : 0.25 to 1.00 ; p = 0.049 ) . The post-hoc analysis on OAC treatment sensitivity supported the benefit of self-management ( HR 0.27 ; 95 % CI : 0.13 to 0.71 ; p = 0.006 ) . Fifteen patients in the SMG died during the study , but none of the deaths was directly associated with anticoagulation therapy . In the RCG , 11 patients died ; of those , three deaths were directly associated with anticoagulation therapy and there was one death of unknown cause . During follow-up , the quality of OAC control was significantly better in the SMG than in the RCG . In elderly patients , long-term self-management of oral anticoagulation is superior for the prevention of major thromboembolic and bleeding complications and for the quality of oral anticoagulation control compared to routine care for a mean follow-up period of three years BACKGROUND Dabigatran is an oral direct thrombin inhibitor that has been shown to be an effective alternative to warfarin in patients with atrial fibrillation . We evaluated the use of dabigatran in patients with mechanical heart valves . METHODS In this phase 2 dose-validation study , we studied two population s of patients : those who had undergone aortic- or mitral-valve replacement within the past 7 days and those who had undergone such replacement at least 3 months earlier . Patients were r and omly assigned in a 2:1 ratio to receive either dabigatran or warfarin . The selection of the initial dabigatran dose ( 150 , 220 , or 300 mg twice daily ) was based on kidney function . Doses were adjusted to obtain a trough plasma level of at least 50 ng per milliliter . The warfarin dose was adjusted to obtain an international normalized ratio of 2 to 3 or 2.5 to 3.5 on the basis of thromboembolic risk . The primary end point was the trough plasma level of dabigatran . RESULTS The trial was terminated prematurely after the enrollment of 252 patients because of an excess of thromboembolic and bleeding events among patients in the dabigatran group . In the as-treated analysis , dose adjustment or discontinuation of dabigatran was required in 52 of 162 patients ( 32 % ) . Ischemic or unspecified stroke occurred in 9 patients ( 5 % ) in the dabigatran group and in no patients in the warfarin group ; major bleeding occurred in 7 patients ( 4 % ) and 2 patients ( 2 % ) , respectively . All patients with major bleeding had pericardial bleeding . CONCLUSIONS The use of dabigatran in patients with mechanical heart valves was associated with increased rates of thromboembolic and bleeding complications , as compared with warfarin , thus showing no benefit and an excess risk . ( Funded by Boehringer Ingelheim ; Clinical Trials.gov numbers , NCT01452347 and NCT01505881 . ) BACKGROUND Warfarin anticoagulation reduces thromboembolic complications in patients with atrial fibrillation or mechanical heart valves , but effective management is complex , and the international normalized ratio ( INR ) is often outside the target range . As compared with venous plasma testing , point-of-care INR measuring devices allow greater testing frequency and patient involvement and may improve clinical outcomes . METHODS We r and omly assigned 2922 patients who were taking warfarin because of mechanical heart valves or atrial fibrillation and who were competent in the use of point-of-care INR devices to either weekly self-testing at home or monthly high- quality testing in a clinic . The primary end point was the time to a first major event ( stroke , major bleeding episode , or death ) . RESULTS The patients were followed for 2.0 to 4.75 years , for a total of 8730 patient-years of follow-up . The time to the first primary event was not significantly longer in the self-testing group than in the clinic-testing group ( hazard ratio , 0.88 ; 95 % confidence interval , 0.75 to 1.04 ; P=0.14 ) . The two groups had similar rates of clinical outcomes except that the self-testing group reported more minor bleeding episodes . Over the entire follow-up period , the self-testing group had a small but significant improvement in the percentage of time during which the INR was within the target range ( absolute difference between groups , 3.8 percentage points ; P<0.001 ) . At 2 years of follow-up , the self-testing group also had a small but significant improvement in patient satisfaction with anticoagulation therapy ( P=0.002 ) and quality of life ( P<0.001 ) . CONCLUSIONS As compared with monthly high- quality clinic testing , weekly self-testing did not delay the time to a first stroke , major bleeding episode , or death to the extent suggested by prior studies . These results do not support the superiority of self-testing over clinic testing in reducing the risk of stroke , major bleeding episode , and death among patients taking warfarin therapy . ( Funded by the Department of Veterans Affairs Cooperative Studies Program ; Clinical Trials.gov number , NCT00032591 . ) BACKGROUND Although prosthetic valves are durable and easy to implant , the need for lifetime warfarin-based anticoagulation restricts their exclusive usage . We investigated if anticoagulation self-management improves outcome in a single-center series . METHODS Between 1994 and 1998 , 765 patients with prosthetic valve replacements were prospect ively enrolled and r and omized to receive conventional anticoagulation management by their primary physician ( group 1 , n = 295 ) or to pursue anticoagulation self-management ( group 2 , n = 470 ) . A study head office was implemented to coordinate and monitor anticoagulation protocol s , international normalized ratios ( INR ) , and adverse events . Patients were instructed on how to obtain and test their own blood sample s and to adjust warfarin dosages according to the measured INR ( target range , 2.5 to 4 ) . RESULTS Mean INR values were slightly yet significantly smaller in group 1 than in group 2 ( 2.8 + /- 0.7 vs 3.0 + /- .6 , p < 0.001 ) . Moreover , INR values of patients with conventional INR management were frequently measured outside the INR target range , whereas those with anticoagulation self-management mostly remained within the range ( 35 % vs 21 % , p < 0.001 ) . In addition , the scatter of INR values was smaller if self-managed . Freedom from thromboembolism at 3 , 12 , and 24 months , respectively , was 99 % , 95 % , and 91 % in group 1 compared with 99 % , 98 % , and 96 % in group 2 ( p = 0.008 ) . Bleeding events were similar in both groups . Time-related multivariate analysis identified INR self-management and higher INR as independent predictors for better outcome . CONCLUSIONS Anticoagulation self-management can improve INR profiles up to 2 years after prosthetic valve replacement and reduce adverse events . Current indications of prosthetic rather than biologic valve implantations may be extended if the benefit of INR self-management is shown by future studies with longer follow-up |
1,217 | 27,159,540 | RECENT FINDINGS Recent clinical trials , systematic review s , and meta-analyses have demonstrated that allergen-specific immunotherapy ( ASI ) , especially sublingual immunotherapy for as short as 12 months , may help improve asthma symptoms and reduce medication usage .
However , studies have not demonstrated overall improvement in pulmonary function tests despite improvement in symptoms .
SUMMARY ASI may change the natural course of allergic asthma by reducing the risk of acute respiratory exacerbations and symptoms .
Additional studies are necessary to examine whether early treatment of allergy sensitivities with ASI may ultimately prevent the progression to asthma | PURPOSE OF REVIEW Asthma and allergic rhinitis are two of the most widespread chronic medical conditions .
Asthma , a condition which encompasses chronic inflammation of the lower airway result ing in expiratory obstruction , may represent an end phase along the allergic disease spectrum ultimately stemming initially from nasal allergic rhinitis and bronchial hyper-reactivity .
The purpose of this review was to evaluate the available published literature over the past 12 months regarding the role of allergy immunotherapy in the treatment of asthma . | BACKGROUND The effect of conventional allergen immunotherapy on allergen-specific T lymphocyte cytokine production is incompletely understood , particularly during the initial phase of treatment . OBJECTIVE The purpose of this study was to prospect ively follow the kinetics of change in CD4(+ ) T cell cytokine secretion during the course of conventional immunotherapy . METHODS Six allergic individuals were treated with extracts of Dermatophagoides farinae/Dermatophagoides pteronyssinus or with rye grass pollen ( Lolium perenne ) allergen , but not both , by using an internally controlled conventional immunotherapy protocol . CD4(+ ) T cells from peripheral blood were examined in vitro at varying intervals after the initiation of immunotherapy by stimulation with D farinae or L perenne group I antigen . The quantity of IL-4 and IFN-gamma produced and its relationship to clinical improvement was determined . RESULTS The ratio of allergen-specific IL-4/IFN-gamma production by CD4(+ ) T cells from 4 of 6 individuals receiving immunotherapy greatly increased during the period when the dose of allergen was increasing . However , after high-dose maintenance therapy was achieved , this ratio decreased in subjects responding clinical ly to , but not in those failing , immunotherapy . In addition , late-phase skin reactions and allergen-specific IgE levels in responding , but not in nonresponding , subjects diminished over the course of immunotherapy . CONCLUSION Conventional immunotherapy may initially exacerbate allergic disease by increasing allergen-specific IL-4 and allergen-specific IgE production . Later clinical improvement is associated with a reduction in allergen-specific IL-4 production and in allergen-specific serum Allergic rhinitis and asthma are examples of allergic airways disease . Despite their differing symptomatology , both disorders affect the mucosal lining of the respiratory tract and are linked by common underlying cellular processes , thus , using the ‘ united airways ’ approach , they can be considered part of the same allergic disease . The conditions are often comorbid , and there is evidence to suggest that allergic rhinitis in children is a significant risk factor for subsequent development of asthma . Management strategies that target the underlying cause of allergic rhinitis in children have the potential to offer additional symptom control above that of symptomatic medications , and prevent disease progression . Specific immunotherapy ( SIT ) is the only currently available treatment that is proven to target the disease in this way . SIT affects the underlying cause of allergic rhinitis , producing changes in antibody responses to allergens . It has been shown to be effective in the reduction of allergic rhinitis symptoms in both children and adults , with effects being sustained for several years after treatment completion . Furthermore , a number of trials provide evidence that SIT may prevent the development of new sensitisations and asthma in children and adults with allergic rhinitis . One such open-label , r and omised controlled study in children/adolescents ( the Preventive Allergy Treatment Study ) showed that significantly fewer patients who received 3 years of SIT for grass/birch pollen-induced allergic rhinitis had developed asthma 10 years after treatment initiation versus controls . Some clinical guidelines acknowledge this potential asthma preventive effect in children and the need for additional data from double-blind , placebo-controlled trials to support these findings Twenty‐seven patients with allergy to house‐dust mite and the clinical symptoms of perennial rhinitis and /or mild asthma were treated with specific immunotherapy ( SIT ) with st and ardized extracts of house‐dust mite for 3 years . The success of therapy was evaluated in yearly intervals OBJECTIVES This report presents health statistics from the 2001 National Health Interview Survey for the civilian noninstitutionalized adult population classified by sex , age , race and Hispanic origin , poverty status , and region of residence for chronic condition prevalence , health status and functional limitations , health care access and utilization , health behaviors , and human immunodeficiency virus ( HIV ) testing . Also , health statistics by education , income , health insurance coverage , marital status , and place of residence are presented for health status and limitations in activity , health care access and utilization , health behaviors , and knowledge and attitudes toward HIV . SOURCE OF DATA The National Health Interview Survey is a multistage probability sample survey conducted annually by interviewers of the U.S. Census Bureau for the Centers for Disease Control and Prevention 's National Center for Health Statistics and is representative of the civilian noninstitutionalized U.S. population . Sociodemographic data are collected for everyone in the family during face-to-face interviews with adults present at the time of the interview . The health information for adults in this report was obtained from one r and omly selected adult per family . HIGHLIGHTS In 2001 , 64 % of adults 18 years of age and over reported excellent or very good health . Fifty-eight percent of adults never participated in any type of vigorous leisure-time physical activity , and 13 % of adults did not have a usual place of health care . Twelve percent of adults had been told by a doctor or health professional that they had heart disease , and 21 % had been told on two or more visits that they had hypertension . Nearly a quarter of all adults were current smokers , and 22 % were former smokers . Based on estimates of body mass index , 36 % of adults were overweight and 23 % were obese INTRODUCTION In a double-blind , placebo-controlled trial ( EudraCT identifier : 2006 - 001795 - 20 ) , the st and ardised quality ( SQ ) house dust mite ( HDM ) sublingual immunotherapy (SLIT)-tablet ( ALK , Denmark ) was investigated . METHOD The trial included 604 subjects , ≥14 years , with mild-moderate HDM allergic asthma . Subjects were r and omised 1:1:1:1 to 1 , 3 or 6 SQ-HDM or placebo once daily . The primary endpoint was reduction in inhaled corticosteroid ( ICS ) after one year . ICS reduction , asthma quality of life question naire ( AQLQ ) and asthma control question naire ( ACQ ) score was analysed post hoc in a subgroup with daily ICS use of 400 - 800 μg and ACQ score of 1 - 1.5 , corresponding to partly controlled asthma ( N = 108 ) . RESULTS The trial met its primary endpoint . In the subgroup , the difference between placebo and 6 SQ-HDM in change from baseline in daily ICS use was 327 μg ( p < 0.0001 ) , while it was 0.52 ( p = 0.010 ) for AQLQ . The treatment effect on ICS reduction and AQLQ was increased for the subgroup versus the residual population ( ICS reduction : p < 0.001 ) ; AQLQ : p = 0.044 ) . CONCLUSION In this subgroup , including only patients with partly controlled asthma , the benefit of 1 year of treatment with SQ HDM SLIT-tablet was significantly higher than for the less severe full population , both in terms of increased asthma control and improved quality of life BACKGROUND Investigations meeting current st and ards are limited for the effect of house dust mite ( HDM ) allergy immunotherapy in asthmatic patients . OBJECTIVE This trial investigated the efficacy and safety of a st and ardized quality ( SQ ; allergen st and ardization method proprietary to the trial sponsor ) HDM SLIT-tablet ( ALK , Hørsholm , Denmark ) in adults and adolescents with HDM respiratory allergic disease . This publication reports the results of the endpoints related to asthma . METHODS Six hundred four subjects 14 years or older with HDM allergic rhinitis and mild-to-moderate asthma were r and omized 1:1:1:1 to double-blind daily treatment with one of 3 active doses ( 1 , 3 , or 6 SQ-HDM ) or placebo . Their use of inhaled corticosteroid ( ICS ) was st and ardized and adjusted at baseline and the end of treatment to the lowest dose providing asthma control . The primary end point was a reduction in ICS dose from the individual subject 's baseline dose after 1 year of treatment . RESULTS The primary analysis revealed a mean difference between 6 SQ-HDM and placebo in the reduction in daily ICS dose of 81 μg ( P = .004 ) . Relative mean and median reductions were 42 % and 50 % for 6 SQ-HDM and 15 % and 25 % for placebo , respectively . No statistically significant differences were observed for the other assessed asthma parameters , reflecting the intended controlled status of the trial subjects . The most common adverse events were local reactions in the mouth . The rate and severity of adverse events were higher for 3 and 6 SQ-HDM than for 1 SQ-HDM and placebo . CONCLUSION Efficacy in mild-to-moderate asthma of 6 SQ-HDM relative to placebo was demonstrated by a moderate statistically significant reduction in the ICS dose required to maintain asthma control . All active doses were well tolerated Although H1 antihistamine compounds ( H1 ) are highly effective in the treatment of allergic rhinitis ( AR ) , their role in the treatment of asthma is still controversial . Because a strong association between AR and bronchial hyperresponsiveness ( BHR ) has been reported , this study was design ed to assess the effect of a new H1 anti histamine , cetirizine ( C ) , on nonspecific BHR in patients with AR . Twelve patients were included in a double‐blind , crossover , placebo‐controlled trial . All patients had positive skin tests for common allergens and showed BHR to inhaled methacholine after specific nasal allergenic challenge . After a washout period of 1 week to ensure the stability of the BHR , the patients received , by crossover r and omization , C 10 mg daily or placebo ( P ) for 2 weeks . After each treatment period , BHR and nasal blocking index ( NBI ) were measured 1 and 6 h after nasal challenge . Bronchial responsiveness was expressed as methacholine PD20 , the provocation dose of methacholine causing a 20 % decrease in FEV1 . Measurements were then performed after 2 weeks of C and after 2 weeks of P. Baseline values of PD20 ( median ) measured before challenge showed no difference after cetirizine or after placebo ( 1.36 mg ) . Results 1 h after allergen did not show significant differences between C ( methacholine PD20=0.522 mg ) and placebo ( methacholine PD20=0.455 mg ) . By contrast , 6 h after challenge , methacholine PD20 was 0.918 mg for C and 0.483 mg for P ( P=0.042 ) . Similarly , NBI showed no change between C and P 1 h after challenge , whereas the difference was significant 6 h after challenge ( P=0.011 ) . These data demonstrate a protective nasal effect of C against BHR measured 6 h after nasal allergen challenge in patients with AR . They suggest that C may be useful in patients with asthma associated with AR The efficacy and safety of sublingual immunotherapy in house dust mite – induced asthma have yet to be firmly established . We report the results of a double‐blind , placebo‐controlled , r and omized clinical trial performed in mainl and China |
1,218 | 30,654,833 | Graphic health warnings were perceived as more effective than text-only warnings , with warnings depicting lung cancer , and oral diseases being perceived as particularly effective .
Health warnings increased viewer fear , anxiety , shock , and guilt and were considered effective in preventing non-smokers from experimenting with tobacco and prompting current smokers to quit .
Plain packaging reduced the attractiveness and other positive attributes of cigarette packaging , with darker colours found to be the most effective .
When used in combination , plain packaging increased the visibility of graphic health warnings , with participants also perceiving them as having an increased tar content and having more serious health risks , and increased thoughts of quitting amongst smokers .
Conclusions Graphic health warnings and plain packaging appear to increase adolescent awareness of the dangers of tobacco use . | Background Graphic health warnings on tobacco packaging and the plain packaging of tobacco products are key tobacco control interventions .
This systematic review investigates the perceptions of adolescents towards these packaging interventions . | Background The U.S. Food and Drug Administration ( FDA ) is working to introduce new graphic warning labels for cigarette packages , the first change in cigarette warnings in more than 25 years . We sought to examine whether warnings discouraged participants from wanting to smoke and altered perceived likelihood of harms among adolescent males and whether these warning effects varied by age . Methods A national sample of 386 non-smoking American males ages 11–17 participated in an online experiment during fall 2010 . We r and omly assigned participants to view warnings using a 2 × 2 between-subjects design . The warnings described a harm of smoking ( addiction or lung cancer ) using text only or text plus an image used on European cigarette package warnings . Analyses tested whether age moderated the warnings ' impact on risk perceptions and smoking motivations . Results The warnings discouraged most adolescents from wanting to smoke , but lung cancer warnings discouraged them more than addiction warnings did ( 60 % vs. 34 % were “ very much ” discouraged , p<.001 ) . Including an image had no effect on discouragement . The warnings affected several beliefs about the harms from smoking , and age moderated these effects . Adolescents said addiction was easier to imagine and more likely to happen to them than lung cancer . They also believed that their true likelihood of experiencing any harm was lower than what an expert would say . Conclusions Our findings suggest that warnings focusing on lung cancer , rather than addiction , are more likely to discourage wanting to smoke among adolescent males and enhance their ability to imagine the harmful consequences of smoking . Including images on warnings had little effect on non-smoking male adolescents ' discouragement or beliefs , though additional research on the effects of pictorial warnings for this at-risk population is needed as the FDA moves forward with developing new graphic labels Objectives To compare adolescents ’ responses to three different styles of cigarette packaging : novelty ( br and ed packs design ed with a distinctive shape , opening style or bright colour ) , regular ( br and ed pack with no special design features ) and plain ( brown pack with a st and ard shape and opening and all br and ing removed , aside from br and name ) . Design Cross-sectional in-home survey . Setting UK . Participants R and om location quota sample of 1025 never smokers aged 11–16 years . Main outcome measures Susceptibility to smoking and composite measures of pack appraisal and pack receptivity derived from 11 survey items . Results Mean responses to the three pack types were negative for all survey items . However , ‘ novelty ’ packs were rated significantly less negatively than the ‘ regular ’ pack on most items , and the novelty and regular packs were rated less negatively than the ‘ plain ’ pack . For the novelty packs , logistic regressions , controlling for factors known to influence youth smoking , showed that susceptibility was associated with positive appraisal and also receptivity . For example , those receptive to the innovative Silk Cut Superslims pack were more than four times as likely to be susceptible to smoking than those not receptive to this pack ( AOR=4.42 , 95 % CI 2.50 to 7.81 , p<0.001 ) . For the regular pack , an association was found between positive appraisal and susceptibility but not with receptivity and susceptibility . There was no association with pack appraisal or receptivity for the plain pack . Conclusions Pack structure ( shape and opening style ) and colour are independently associated , not just with appreciation of and receptivity to the pack , but also with susceptibility to smoke . In other words , those who think most highly of novelty cigarette packaging are also the ones who indicate that they are most likely to go on to smoke . Plain packaging , in contrast , was found to directly reduce the appeal of smoking to adolescents 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 Cigarette package health warnings can be an important and low-cost means of communicating the health risks of smoking . We examined whether viewing health warnings in an experimental study influenced beliefs about the health effects of smoking , by conducting surveys with ~500 adult male smokers and ~500 male and female youth ( age 16–18 ) in Beijing , China ( n = 1070 ) , Mumbai area , India ( n = 1012 ) , Dhaka , Bangladesh ( n = 1018 ) , and Republic of Korea ( n = 1362 ) . Each respondent was r and omly assigned to view and rate pictorial health warnings for 2 of 15 different health effects , after which they reported beliefs about whether smoking caused 12 health effects . Respondents who viewed relevant health warnings ( vs. other warnings ) were significantly more likely to believe that smoking caused that particular health effect , for several health effects in each sample . Approximately three-quarters of respondents in China ( Beijing ) , Bangladesh ( Dhaka ) , and Korea ( which had general , text-only warnings ) thought that cigarette packages should display more health information , compared to approximately half of respondents in the Mumbai area , India ( which had detailed pictorial warnings ) . Pictorial health warnings that convey the risk of specific health effects from smoking can increase beliefs and knowledge about the health consequences of smoking , particularly for health effects that are lesser-known Objectives : To examine the impact of health warnings on smokers by comparing the short-term impact of new graphic ( 2006 ) Australian warnings with : ( i ) earlier ( 2003 ) United Kingdom larger text-based warnings ; ( ii ) and Canadian graphic warnings ( late 2000 ) ; and also to extend our underst and ing of warning wear-out . Methods : The International Tobacco Control Policy Evaluation Survey ( ITC Project ) follows prospect i ve cohorts ( with replenishment ) of adult smokers annually ( five waves : 2002–2006 ) , in Canada , United States , UK and Australia ( around 2000 per country per wave ; total n = 17 773 ) . Measures were of pack warning salience ( reading and noticing ) ; cognitive responses ( thoughts of harm and quitting ) ; and two behavioural responses : forgoing cigarettes and avoiding the warnings . Results : All four indicators of impact increased markedly among Australian smokers following the introduction of graphic warnings . Controlling for date of introduction , they stimulated more cognitive responses than the UK ( text-only ) changes , and were avoided more , did not significantly increase forgoing cigarettes , but were read and noticed less . The findings also extend previous work showing partial wear-out of both graphic and text-only warnings , but the Canadian warnings have more sustained effects than UK ones . Conclusions : Australia ’s new health warnings increased reactions that are prospect ively predictive of cessation activity . Warning size increases warning effectiveness and graphic warnings may be superior to text-based warnings . While there is partial wear-out in the initial impact associated with all warnings , stronger warnings tend to sustain their effects for longer . These findings support arguments for governments to exceed minimum FCTC requirements on warnings INTRODUCTION Cigarette packaging is among the most prominent forms of tobacco marketing . This study examined the impact of cigarette pack design among young women in the United States . METHOD A national sample of 18- to 19-year-old females in the United States completed an online survey in February 2010 . Participants were r and omized to view eight cigarette packs design ed according to one of four experimental conditions : fully br and ed female packs , same packs without descriptors ( e.g. , " slims " ) , same packs without br and imagery or descriptors ( " plain " packs ) , and br and ed non-female br and s. Participants rated packs on measures of appeal and health risk and completed a behavioral pack selection task . RESULTS Fully br and ed female packs were rated significantly more appealing than the same packs without descriptors , " plain " packs , and non-female-br and ed packs . Female-br and ed packs were associated with a greater number of positive attributes including glamour , slimness , and attractiveness and were more likely to be perceived as less harmful . Approximately 40 % of smokers and nonsmokers requested a pack at the end of the study ; female-br and ed packs were 3 times more likely to be selected than plain packs . CONCLUSION Plain packaging and removing descriptors such as " slims " from cigarette packs may reduce smoking susceptibility among young women CONTEXT There is no vali date d , theory-based tool for assessing the onset of nicotine dependence . However , the use of all addictive substances can result in a loss of autonomy . We propose that nicotine dependence begins when autonomy is lost , ie , when the sequelae of tobacco use , either physical or psychological , present a barrier to quitting . OBJECTIVES To test the autonomy theory of nicotine dependence , and to evaluate the Hooked on Nicotine Checklist ( HONC ) as a measure of the loss of autonomy over tobacco use . DESIGN The psychometric performance and concept validity of the HONC were evaluated in a 30-month prospect i ve longitudinal study of the natural history of tobacco use in a cohort of 679 seventh- grade students . RESULTS As hypothesized , endorsement of a single item on the HONC was associated with a failed attempt at smoking cessation ( odds ratio [ OR ] , 29 ; 95 % confidence interval [ CI ] , 13 - 65 ) , continued smoking until the end of follow-up ( OR , 44 ; 95 % CI , 17 - 114 ) , and daily smoking ( OR , 58 ; 95 % CI , 24 - 142 ) . Scores on the HONC correlated with the maximum amount smoked ( r = 0.65 ; P<.001 ) and the maximum frequency of smoking ( r = 0.79 ; P<.001 ) . Internal reliability was 0.94 . A 1-factor solution explained 66 % of the total variance . CONCLUSIONS The data support the autonomy theory that dependence begins with the loss of autonomy . The autonomy theory represents a potentially useful alternative to current concepts of nicotine dependence for adolescents , and the HONC appears to measure lost autonomy in adolescents . Construct validity was demonstrated by its utility in predicting failed cessation and the progression of tobacco use . In addition , the psychometric properties were excellent PURPOSE Cigarette packaging is the most prominent form of tobacco marketing remaining in countries such as the United Kingdom . The current study examined perceptions of cigarette packaging among female youth and the potential impact of " plain " cigarette packaging regulations . METHODS A national sample of 947 16- to 19-year-old female subjects in the United Kingdom completed an online survey . Participants were r and omized to view 10 cigarette packs design ed according to one of four experimental conditions : fully br and ed female packs , the same packs without descriptor words , the same packs without br and imagery or descriptors ( " plain " packs ) , and br and ed non-female br and s. Participants rated packs on measures of appeal and health risk , positive smoker image , and completed a behavioral pack selection task . RESULTS Plain packs were rated as the least appealing and worse tasting compared with all other conditions . Plain packs were also associated with fewer false beliefs about health risks compared with br and ed packs . Removing br and descriptors from packs significantly reduced measures of appeal and taste , particularly for br and s with flavor descriptors , such as cherry and vanilla . Plain packs were significantly less likely to be associated with positive images , such as glamour , sophistication , and slimness . Most importantly , respondents were significantly less likely to accept a pack of cigarettes when offered only plain versus br and ed packs ( p = .026 ) . CONCLUSIONS Marketing in the form of pack br and ing remains a potent tool for increasing the appeal of tobacco products to young women . The findings provide empirical support for plain cigarette packaging regulations in Australia to be implemented in 2012 Objectives To measure young people 's perceptions of tobacco packaging according to two current pieces of legislation : The EU Tobacco Products Directive ( TPD ) and Irel and 's Public Health ( St and ardisation of Tobacco Products ) Act . Design Within-subject experimental cross-sectional survey of a representative sample of secondary school students . School-based pen and paper survey . Setting 27 secondary schools across Irel and , r and omly stratified for size , geographic location , gender , religious affiliation and school-level socioeconomic status . Data were collected between March and May 2014 . Participants 1378 fifth year secondary school students aged 16–17 in Irel and . Main outcome measures Young people 's perceptions of attractiveness , health risk and smoker characteristics of packs according to EU and Irish br and ing and packaging guidelines . Results Packs with more br and ing elements were thought to be healthier than st and ardised packs for Silk Cut ( χ2=158.58 , p<0.001 ) , Marlboro ( χ2=113.65 , p<0.001 ) , and Benson and Hedges ( χ2=137.95 , p<0.001 ) br and s. Generalized estimating equation binary regressions found that gender was a significant predictor of pack attractiveness for Silk Cut , with females being more likely to find the EU packs attractive ( β=−0.45 , p=0.007 ) . Gender was a significant predictor for females with regards to the perceived popularity of the Silk Cut br and ( β=−0.37 , p=0.03 ) . Conclusions The removal of br and identifiers , including colour , font and embossing , reduces the perceived appeal of cigarette packs for young people across all three tested br and s. Packs st and ardised according to Irish legislation are perceived as less attractive , less healthy and smoked by less popular people than packs which conform to the EU TPD 2014 guidelines Purpose Pictorial health warnings on cigarette packages are a prominent and effective means of communicating the risks of smoking ; however , there is little research on effective types of message content and socio-demographic effects . This study tested message themes and content of pictorial warnings in Mexico . Methods Face-to-face surveys were conducted with 544 adult smokers and 528 youth in Mexico City . Participants were r and omized to view 5–7 warnings for two of 15 different health effects . Warnings for each health effect included a text-only warning and pictorial warnings with various themes : “ graphic ” health effects , “ lived experience ” , symbolic images , and testimonials . Results Pictorial health warnings were rated as more effective than text-only warnings . Pictorial warnings featuring “ graphic ” depictions of disease were significantly more effective than symbolic images or experiences of human suffering . Adding testimonial information to warnings increased perceived effectiveness . Adults who were female , older , had lower education , and intended to quit smoking rated warnings as more effective , although the magnitude of these differences was modest . Few interactions were observed between socio-demographics and message theme . Conclusions Graphic depictions of disease were perceived by youth and adults as the most effective warning theme . Perceptions of warnings were generally similar across socio-demographic groups Plain cigarette packaging , which seeks to remove all br and imagery and st and ardize the shape and size of cigarette packs , represents a novel policy measure to reduce the appeal of cigarettes . Plain packaging has been studied primarily in high-income countries like Australia and the UK . It is unknown whether the effects of plain packaging may differ in low- and -middle income countries with a shorter history of tobacco regulation , such as Mexico . An experimental study was conducted in Mexico City to examine perceptions of br and ed and plain cigarette packaging among smoking and non-smoking Mexican adolescents ( n = 359 ) . Respondents were r and omly assigned to a br and ed or plain pack condition and rated 12 cigarette packages for appeal , taste , harm to health and smoker-image traits . As a behavioral measure of appeal , respondents were offered ( although not given ) four cigarette packs ( either br and ed or plain ) and asked to select one to keep . The findings indicated that br and ed packs were perceived to be more appealing ( β = 3.40 , p < 0.001 ) and to contain better tasting cigarettes ( β = 3.53 , p < 0.001 ) , but were not perceived as less harmful than plain packs . Participants rated people who smoke the br and ed packs as having relatively more positive smoker-image traits overall ( β = 2.10 , p < 0.001 ) , with particularly strong differences found among non-smokers for the traits ' glamorous ' , ' stylish ' , ' popular ' and ' sophisticated ' ( p < 0.001 ) . No statistically significant difference was found for the proportion of youth that accepted when offered br and ed compared with plain packs . These results suggest that plain packaging may reduce br and appeal among Mexican youth , consistent with findings in high-income countries BACKGROUND Graphical tobacco product labelling is a prominent source of health information and has an important position among tobacco control initiatives . However , little is known about its effectiveness among adolescents . With this above in mind , we aim ed to research into how adolescents perceive the proposed EU graphic tobacco product warning labels as an effective means of preventing smoking initiation in comparison to the current EU text-only warning labels . METHODS Five hundred seventy four adolescents ( 13 - 18 , 54 % male ) from Greece were privately interviewed , with the use of a digital question naire and r and omly shown seven existing EU text-only and proposed EU graphic warning labels . Non-smoking respondents were asked to compare and rate the warnings effectiveness in regard to preventing them from smoking on a 1 - 5 Likert type scale . RESULTS Irrespective of the warning category shown , on all occasions , non-smoking adolescents rated the suggested EU graphic labels as more effective in preventing them from smoking in comparison to the existing EU text-only warnings . Controlling for gender , age , current smoking status and number of cigarettes smoked per month , younger adolescents were found to opt for graphic warnings more often , and also perceive graphic warning labels as a more effective means of preventing them from smoking , in comparison to their elder peers ( P < 0.001 ) . CONCLUSIONS The proposed EU graphic warning labels may play an important role in preventing of smoking initiation during the crucial years of early adolescence when smoking experimentation and early addiction usually take place PURPOSE To examine the effect of plain packaging on adolescents ' perceptions of cigarette packs , attributes of smokers , and expectations of cigarette taste , and to identify the effect of increasing the size of pictorial health warnings on appraisal of plain packs . METHODS We used a 5 ( degree of plain packaging and graphic health warning)x 3 ( br and type ) between-subjects experimental design , using a Web-based methodology to expose adolescents to one r and omly selected cigarette pack , during which respondents completed ratings . RESULTS When br and elements such as color , br and ed fonts , and imagery were progressively removed from cigarette packs , adolescents perceived packs to be less appealing , rated attributes of a typical smoker of the pack less positively , and had more negative expectations of cigarette taste . Pack appeal was reduced even further when the size of the pictorial health warning on the most plain pack was increased from 30 % to 80 % of the pack face , with this effect apparent among susceptible nonsmokers , experimenters , and established smokers . CONCLUSIONS Removing as much br and information from cigarette packs as possible is likely to reduce positive cigarette br and image associations among adolescents . By additionally increasing the size of pictorial health warnings , positive pack perceptions of those who are at greater risk of becoming regular addicted adult smokers are most likely to be reduced INTRODUCTION In 2010 , the U.S. Food and Drug Administration ( FDA ) developed 36 proposed health warnings for cigarette packages , from which 9 were subsequently selected for implementation . The current study aim ed to evaluate the perceived efficacy of the 36 proposed FDA warnings . METHODS Web-based surveys were conducted with 783 adult smokers and 510 youth in United States . Participants were r and omized to view and rate two sets of 6 - 7 warnings , each set corresponding to one of nine health effect statements required under the Tobacco Control Act . Warnings included all 36 FDA -proposed warnings and additional warnings for comparison . RESULTS Youth and adults rated individual warnings similarly ; in all cases where differences were found , youth perceived warnings as more effective . Comparisons on specific elements indicated that warnings were perceived as more effective if they were : full color ( vs. black and white ) , featured real people ( vs. comic book style ) , contained graphic images ( vs. nongraphic ) , and included a telephone " quitline " number or personal information . Few sociodemographic differences were observed in overall perceived effectiveness : younger respondents , non-White respondents , and smokers intending to quit rated warnings higher . CONCLUSIONS Seven of the nine health warnings selected by the FDA for implementation were among the proposed warnings rated as most effective in the current study . However , the warning(s ) added for comparison were rated higher than the FDA -selected warning for five of the nine sets , suggesting some warnings could be improved for greater impact . The findings support the inclusion of a telephone " quitline " number and reinforce the importance of depicting " real " people and health effects |
1,219 | 31,817,324 | Nigella sativa was shown to significantly improve laboratory parameters of hyperglycemia and diabetes control after treatment with a significant fall in fasting blood glucose , blood glucose level 2 h postpr and ial , glycated hemoglobin , and insulin resistance , and a rise in serum insulin .
In conclusion , these findings suggested that Nigella sativa could be used as an adjuvant for oral antidiabetic drugs in diabetes control | Diabetes mellitus is one of the most prevalent metabolic disorders that affect people of all genders , ages , and races .
Medicinal herbs have gained wide attention from research ers and have been considered to be a beneficial adjuvant agent to oral antidiabetic drugs because of their integrated effects .
Concerning the various beneficial effects of Nigella sativa , this systematic review aims to provide comprehensive information on the effects of Nigella sativa on glucose and insulin profile status in humans . | AIM : The seeds of the Nigella sativa plant have been used to promote health and fight disease for centuries , especially in the Middle East and in Southeast Asia . This plant has been a focus of much research . This clinical study was undertaken to know the adjuvant effect of N. sativa oil on various clinical and biochemical parameters of the insulin resistance syndrome . MATERIAL S AND METHODS : This prospect i ve study was conducted at a tertiary health care center in North India . After confirmation of diagnosis , 60 patients who fulfilled the inclusion and exclusion criteria were enrolled in this study . Written informed consent was taken from all the patients enrolled . Approval from the institutional ethical committee was also obtained . The patients were divided into two groups of 30 each . In group I ( the st and ard group ) , patients were advised tablet atorvastatin 10 mg once a day and tablet metformin 500 mg twice a day for a period of 6 weeks . In group II ( the N. sativa group ) , the patients were advised tablet atorvastatin 10 mg once a day , tablet metformin 500 mg twice a day , and N. sativa oil 2.5 ml twice daily for a period of 6 weeks . Fasting and postpr and ial blood glucose , fasting lipid profile , and waist circumference were recorded before therapy and after completion of therapy . RESULT : The treatment group showed significant ( P < 0.05 ) improvement with reference to total cholesterol , low density lipoprotein cholesterol ( LDL-C ) , and fasting blood glucose ( P < 0.05 ) . CONCLUSION : N. sativa oil was found to be effective as an add-on therapy in patients of insulin resistance syndrome . N. sativa oil has a significant activity in diabetic and dyslipidemic patients Abstract Objective : To determine the relation between exposure to glycaemia over time and the risk of macrovascular or microvascular complications in patients with type 2 diabetes . Design : Prospect i ve observational study . Setting : 23 hospital based clinics in Engl and , Scotl and , and Northern Irel and . Participants : 4585 white , Asian Indian , and Afro-Caribbean UKPDS patients , whether r and omised or not to treatment , were included in analyses of incidence ; of these , 3642 were included in analyses of relative risk . Outcome measures : Primary predefined aggregate clinical outcomes : any end point or deaths related to diabetes and all cause mortality . Secondary aggregate outcomes : myocardial infa rct ion , stroke , amputation ( including death from peripheral vascular disease ) , and microvascular disease ( predominantly retinal photo-coagulation ) . Single end points : non-fatal heart failure and cataract extraction . Risk reduction associated with a 1 % reduction in up date d mean HbA1c adjusted for possible confounders at diagnosis of diabetes . Results : The incidence of clinical complications was significantly associated with glycaemia . Each 1 % reduction in up date d mean HbA1c was associated with reductions in risk of 21 % for any end point related to diabetes ( 95 % confidence interval 17 % to 24 % , P<0.0001 ) , 21 % for deaths related to diabetes ( 15 % to 27 % , P<0.0001 ) , 14 % for myocardial infa rct ion ( 8 % to 21 % , P<0.0001 ) , and 37 % for microvascular complications ( 33 % to 41 % , P<0.0001 ) . No threshold of risk was observed for any end point . Conclusions : In patients with type 2 diabetes the risk of diabetic complications was strongly associated with previous hyperglycaemia . Any reduction in HbA1c is likely to reduce the risk of complications , with the lowest risk being in those with HbA1c values in the normal range ( < 6.0 % ) UNLABELLED Diabetes mellitus is a common chronic disease affecting millions of people world wide . St and ard treatment is failing to achieve required correction of blood glucose in many patients . Therefore , there is a need for investigating potential hypoglycemic drugs or herbs to improve glycemic control in diabetic patients . Nigella sativa seeds were used as an adjuvant therapy in patients with diabetes mellitus type 2 added to their anti-diabetic medications . A total of 94 patient were recruited and divided r and omly into three dose groups . Capsules containing Nigella sativa were administered orally in a dose of 1 , 2 and 3 gm/day for three months . The effect of Nigella sativa on the glycemic control was assessed through measurement of fasting blood glucose ( FBG ) , blood glucose level 2 hours postpr and ially ( 2 hPG ) , and glycosylated hemoglobin ( HbA1c ) . Serum C-peptide and changes in body weight were also measured . Insulin resistance and beta-cell function were calculated usin the homeostatic model assessment ( HOMA2 ) . Nigella sativa at a dose of 2 gm/day caused significant reductions in FBG , 2hPG , and HbA1 without significant change in body weight . Fasting blood glucose was reduced by an average of 45 , 62 and 56 mg/dl at 4 , 8 and 12 weeks respectively . HbAlC was reduced by 1.52 % at the end of the 12 weeks of treatment ( P<0.0001 ) . Insulin resistance calculated by HOMA2 was reduced significantly ( P<0.01 ) , while B-cell function was increased ( P<0.02 ) at 12 weeks of treatment . The use of Nigella sativa in a dose of 1 gm/day also showed trends in improvement in all the measured parameters but it was not statistically significant from the baseline . However , no further increment in the beneficial response was observed with the 3 gm/day dose . The three doses of Nigella sativa used in the study did not adversely affect either renal functions or hepatic functions of the diabetic patients throughout the study period . IN CONCLUSION the results of this study indicate that a dose of 2 gm/ day of Nigella sativa might be a beneficial adjuvant to oral hypoglycemic agents in type 2 diabetic patients |
1,220 | 31,949,547 | Conclusion Moxibustion treatment for KOA is more effective than the positive control ( western medicine ) or negative control ( placebo moxibustion or no treatment or UC ) , and there were fewer adverse reactions to moxibustion . | Background Knee osteoarthritis ( KOA ) seriously affects people 's life .
Therefore , it has already become a worldwide health concern .
Moxibustion has a significant clinical effect on KOA .
This systematic review and meta- analysis is performed to renew previous studies and strictly evaluate the quality of RCT and thus test the effect and safety of moxibustion for KOA .
Objective To evaluate the effectiveness and safety of moxibustion treatment for alleviating pain and improving lower limb function for patients with KOA . | Introduction Our objective was to compare the effectiveness and safety of traditional Chinese moxibustion to that of sham moxibustion in patients with chronic knee osteoarthritis ( KOA ) pain . Methods We conducted a r and omized placebo-controlled trial involving 110 patients with KOA who met the inclusion criteria . These patients r and omly received either active moxibustion ( n = 55 ) or sham moxibustion control ( n = 55 ) at acupoints Dubi ( ST 35 ) , extra-point Neixiyan ( EX-LE 4 ) , and an Ashi ( tender ) point three times a week for 6 weeks . Effects were evaluated with Western Ontario and McMaster Universities ’ Osteoarthritis Index ( WOMAC VA 3.1 ) criteria at the end of the course of treatment and 3 , 12 , and 24 weeks after the initial treatment . Results The WOMAC pain scores showed greater improvement in the active treatment group than in control at weeks 3 ( P = 0.012 ) , 6 ( P < 0.001 ) , 12 ( P = 0.002 ) , and 24 ( P = 0.002 ) as did WOMAC physical function scores of the active treatment group at week 3 ( P = 0.002 ) , 6 ( P = 0.015 ) , and 12 ( P < 0.001 ) but not 24 ( P = 0.058 ) . Patients and practitioners were blinded successfully , and no significant adverse effects were found during the trial . Conclusions A 6-week course of moxibustion seems to relieve pain effectively and improve function in patients with KOA for up to 18 weeks after the end of treatment . Moxibustion treatment appears to be safe , and the usefulness of the novel moxa device was vali date d . Trial registration Current controlled trial : IS RCT N68475405 . Registered 4 April 2014 Objective . To observe the effects of traditional Chinese moxibustion , compared with sham moxibustion , on the quality of life ( QOL ) in patients with chronic knee osteoarthritis ( KOA ) . Methods . This is a r and omized double-blinded , placebo-controlled trial . 150 patients with KOA were r and omly allocated to either a true moxibustion treatment ( n = 77 ) or a sham moxibustion treatment ( n = 73 ) three times a week for six weeks . The QOL of patients was evaluated with SF-36 at baseline and 3 , 6 , and 12 weeks after baseline . Results . 136 patients were available for analysis . Participants in the true moxibustion group experienced statistically significantly greater improvement in GH ( general health ) scores than the sham group at week 6 ( P = 0.015 ) and week 12 ( P = 0.029 ) . Participants in the true moxibustion group experienced statistically significantly greater improvement in VT ( vitality ) scores than the sham group at week 12 ( P = 0.042 ) . No significant adverse effects were found during the trial . Conclusion . A 6-week moxibustion treatment seems to improve general health and vitality , which are associated with physical and mental quality of life , in patients with KOA up to 12 weeks , relative to credible sham moxibustion . This trial is registered with Clinical trials.gov IS RCT N68475405 Introduction This study tested the effectiveness of moxibustion on pain and function in chronic knee osteoarthritis ( KOA ) and evaluated safety . Methods A multi-centre , non-blinded , parallel-group , r and omised controlled trial compared moxibustion with usual care ( UC ) in KOA . 212 South Korean patients aged 40–70 were recruited from 2011–12 , stratified by mild ( Kellgren/Lawrence scale grade s 0/1 ) and moderate-severe KOA ( grade s 2/3/4 ) , and r and omly allocated to moxibustion or UC for four weeks . Moxibustion involved burning mugwort devices over acupuncture and Ashi points in affected knee(s ) . UC was allowed . Korean Western Ontario and McMaster Universities Question naire ( K-WOMAC ) , Short Form 36 Health Survey ( SF-36v2 ) , Beck Depression Inventory ( BDI ) , physical performance test , pain numeric rating scale ( NRS ) and adverse events were evaluated at 5 and 13 weeks . K-WOMAC global score at 5 weeks was the primary outcome . Results 102 patients ( 73 mild , 29 moderate-severe ) were allocated to moxibustion , 110 ( 77 mild , 33 moderate-severe ) to UC . K-WOMAC global score ( moxibustion 25.42+/−SD 19.26 , UC 33.60+/−17.91 , p<0.01 , effect size = 0.0477 ) , NRS ( moxibustion 44.77+/−22.73 , UC 56.23+/−17.71 , p<0.01 , effect size = 0.0073 ) and timed-st and test ( moxibustion 24.79+/−9.76 , UC 25.24+/−8.84 , p = 0.0486 , effect size = 0.0021 ) were improved by moxibustion at 5 weeks . The primary outcome improved for mild but not moderate-severe KOA . At 13 weeks , moxibustion significantly improved the K-WOMAC global score and NRS . Moxibustion improved SF-36 physical component summary ( p = 0.0299 ) , bodily pain ( p = 0.0003 ) , physical functioning ( p = 0.0025 ) and social functioning ( p = 0.0418 ) at 5 weeks , with no difference in mental component summary at 5 and 13 weeks . BDI showed no difference ( p = 0.34 ) at 5 weeks . After 1158 moxibustion treatments , 121 adverse events included first ( n = 6 ) and second degree ( n = 113 ) burns , pruritus and fatigue ( n = 2 ) . Conclusions Moxibustion may improve pain , function and quality of life in KOA patients , but adverse events are common . Limitations included no sham control or blinding . Trial Registration Clinical Research Information Service ( CRIS ) OBJECTIVE To observe the effect of Aconite cake-separated moxibustion on primary knee osteoarthritis of liver and kidney deficiency type . METHODS Fifty-six cases of such disease ( 80 knees ) were r and omly divided into a cake-separated moxibustion group ( 41 knees ) with Neixiyan ( EX-LE 5 ) , Dubi ( ST 35 ) , Yinlingquan ( SP 9 ) etc . selected , and a western medicine group ( 39 knees ) were treated with oral administration of Sodium Diclofenate Slow-released Tablet . RESULTS The cumulative score for symptoms and signs was ( 37.41 + /- 6.61 ) points before treatment and ( 9.37 + /- 8.15 ) points after treatment in the cake-separated moxibustion group and ( 37.64 - 6.00 ) points before treatment and ( 12.05 + /- 8.83 ) points after treatment in the western medicine group , with a very significant difference before and after treatment in the two groups ( P < 0.01 ) ; two months after treatment , it was ( 11.71 + /- 8.69 ) points in the cake-separated moxibustion group and ( 15.95 + /- 9.96 ) points in the western medicine group , the former being better than the latter ( P < 0.05 ) . After the end of treatment , there was no significant difference in the comprehensive therapeutic effect between the two groups ( P > 0.05 ) , the cured and markedly effective rate was 63.4 % in the cake-separated moxibustion group and 48.7 % in the western medicine group , but two months after treatment , the cured and markedly effective rate of 56.1 % in the cake-separated moxibustion group was better than 33.3 % in the western medicine group ( P < 0.05 ) . CONCLUSION Aconite cake-separated moxibustion has an ideal therapeutic effect on primary knee osteoarthritis of liver and kidney deficiency type , and the therapeutic effect at anaphase is better than that of Sodium Diclofenate Slow-released Tablet OBJECTIVE To investigate the role of adenosine tri-phosphate ( ATP ) purinergic signaling in mast cells ( MCs ) modulated by heat to further underst and the molecular mechanisms of moxibustion . METHODS Skin temperatures induced by monkshood cake moxibustion were evaluated by measuring the Neiguan acupoint ( PC 6 ) from 31 participants with a digital thermocouple thermometer . Temperatures of 43 ° C and 52 ° C were applied to cultured human leukemia mast cell line HMC-1 in vitro . Calcium fluorescence was applied to detect intracellular Ca2 + ( [ Ca2 + ] ) . Extracellular ATP contents were measured by luciferin-luciferase assay . RESULTS Maximum skin temperatures mostly ranged from 40 - 45 ° C , but some reached up to 50 ° C . Both 43 ° C and 52 ° C induced MC degranulation , which was accompanied by an increase in [ Ca2 + ] and ATP release . Complexing extracellular Ca2 + with 5 mM ethylene glycol-bis ( β-aminoethyl ether)-N , N , N',N'-tetraacetic acid ( EGTA ) inhibited the noxious , heat-induced elevation of [Ca2+]i and prevented the enhanced ATP secretion by those . cells at 52 ° C , but not 43 ° C . CONCLUSION Monkshood cake moxibustion can generate heat sufficient to trigger cellular events of MCs , including degranulation , [Ca2+]i elevation , and ATP release , suggesting that purinergic signals originating from MCs are possibly the initiating response of acupoints to moxibustion OBJECTIVE To evaluate the clinical efficacy of warm-needling moxibustion for knee osteoarthritis ( KOA ) , and to explore its effects on isokinetic strength of lower limb muscle . METHODS Fifty cases of KOA were r and omly divided into an observation group ( 25 cases ) and a control group ( 21 cases ) , but 4 cases lost contact . The observation group was treated with warm-needling moxibustion at Dubi ( ST 35 ) , Neixiyan ( EX-LE 4 ) , Xuehai ( SP 10 ) , Liangqiu ( ST 34 ) , Yinlingquan ( SP 9 ) , Yanglingquan ( GB 34 ) , Weizhong ( BL 40 ) , Heyang ( BL 55 ) and Fengshi ( GB 31 ) for 40 min per treatment . The first 6 treatments were given once a day , and the last 6 treatments were given once every other day . 12 treatments were taken as one course , and totally 3-week treatment was given . No treatment was given in the control group for 3 weeks . The isokinetic strength of extensor muscle and flexor muscle , including the total work , absolute peak torque ( aPT ) and relative peak torque ( rPT ) , and Western Ontario and McMaster Universities Arthritis Index ( WOMAC ) , and comprehensive efficacy were observed and compared in the two groups . RESULTS Compared before treatment , the total work , aPT and rPT of the extensor and flexor muscle increased significantly after treatment in the observation group ( P<0.01 , P<0.05 ) , but the flextion/extention ratio was lowered ( P<0.05 ) . In the control group , aPT and rPT of flexor muscle were reduced after treatment ( P<0.05 , P<0.01 ) . The total work , aPT and rPT of the extensor muscle in the observation group were higher than those in the control group after treatment ( P<0.05 , P<0.01 ) , but the flextion/extention ratio was lowered ( P<0.05 ) . The item score and total score of WOMAC were reduced in the observation group after treatment ( all P<0.01 ) , but no significant change was observed in the control group ( all P>0.05 ) . The pain score , stiffness scores and total score of WOMAC in the observation group were lower than those in the control group ( P<0.01 , P<0.05 ) ; the score of daily function activities was declined in the observation group , but not significantly different from that in the control group ( P>0.05 ) . The total effective rate was 88.0 % ( 22/25 ) in the observation group . CONCLUSIONS Warm-needling moxibustion could relieve pain , improve function and muscle balance , strengthen extensor and flexor muscle power , especially extensor , which has superior clinical efficacy OBJECTIVE To investigate hip or knee symptoms in older persons from a longitudinal , population perspective , and to determine the impact of persistent hip or knee pain on general health status over time . METHODS A postal question naire was sent to a r and om sample of 5,500 individuals ages > or = 65 years containing the Short Form 36 ( SF-36 ) general health survey , Lequesne hip and knee indices , and a hip/knee pain severity item . Respondents reporting hip or knee symptoms at baseline received an identical question naire 12 months later . Respondents were classified into a persistent pain group with either hip or knee pain at both baseline and followup , and a non-persistent pain group who reported hip or knee pain at baseline but no pain at followup . RESULTS At baseline , 1,305 ( 40.7 % ) of 3,210 eligible respondents reported hip or knee pain . At 1 year , 1,072 ( 82.1 % ) of 1,305 individuals responded , of whom 820 ( 76.5 % ) remained symptomatic ( the persistent group ) . In multivariate analysis , baseline factors identified as strongly related to having persistent pain were maximum Lequesne score ( odds ratio [ OR ] 1.09 , P < 0.001 ) , maximum hip/knee pain score ( OR 1.61 , P < 0.001 ) , and number of painful hip and knee joints at baseline ( OR 1.48 , P = 0.004 ) . Following adjustment for age , sex , and baseline score , differences in mean SF-36 change scores of the 2 groups were significant for all dimensions except for mental health . CONCLUSION In older persons , a symptomatic hip or knee frequently progresses in terms of worsening symptoms and accrual of other symptomatic hip or knee joints . The impact of persistent symptoms on general health is substantial OBJECTIVE To assess the short-term and long-term therapeutic effect of warming needle moxibustion for treatment of knee osteoarthritis . METHODS Ninety cases were r and omly divided into a warming needle moxibustion group , a western medicine group and a waiting group , 30 cases in each group . The warming needle moxibustion group was treated with warming needle moxibustion on Xuehai ( SP 10 ) , Dubi ( ST 35 ) and Zusanli ( ST 36 ) , etc . ; the western medicine group was treated with oral administration of Ibuprofen sustained release capsule ; the waiting group did not receive any treatment . Western Ontario and McMaster University Osteoarthritis Index ( WOMAC ) and Chinese version of SF-16 were used to assess the therapeutic effect before treatment , after treatment and 10 weeks after treatment . RESULTS After treatment for 2 weeks , the total effective rate was 86.7 % in the warming needle moxibustion group , 90.0 % in the western medicine group , and 60.0 % in the waiting group , both the warming needle moxibustion group and the western medicine group being significantly better than the waiting group ( both P<0.05 ) and with no significant difference between the warming needle moxibustion group and the western medicine group ( P>0.05 ) ; 10 weeks after treatment , the total effective rate of 83.3 % in the warming needle moxibustion group was better than that of 60.0 % in the western medicine group ( P<0.05 ) . There were no significant differences in comparison of WOMAC and SF-16 scores after treatment between the warming needle moxibustion group and the western medicine group , and the warming needle moxibustion group in improvement of these scores was superior to the western medicine group ( P<0.01 , P<0.05 ) . CONCLUSION The therapy of warming needle moxibustion is effective for treatment of knee osteoarthritis , and the short-term therapeutic effect is same as that of oral administration of Ibuprofen and the long-term therapeutic effect is better than that of Ibuprofen Objective The aim of this study was to investigate the difference of efficacy between conventional moxibustion ( CM ) and smoke-free moxibustion ( SM ) for patients with osteoarthritis of the knee ( KOA ) . Methods This is a multicentre , r and omized , single blinded , parallel-group clinical trial . Patients with KOA were r and omly allocated to CM group ( 69 ) and SM group ( 69 ) in 7 hospitals of China . Moxibustion treatment in 12 sessions over 4 weeks was administrated at 3 acupuncture points ( EX-LE4 , ST35 , and ST36 ) . Patients completed st and ard question naires at baseline and after 2 weeks , 4 weeks , 8 weeks , and 12 weeks . The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) from the baseline to 4 weeks . The secondary outcomes include Visual Analogue Scale ( VAS ) and Patient Global Assessment score ( PGA ) . Results Analyses showed that the WOMAC score improved in pain ( 95 % CI,-0.1[-1.2 to 0.9 ] , p=0.76 ) , stiffness ( 95 % CI,-0.1 [ -0.5 to 0.3 ] , p=0.71 ) , and function ( 95 % CI , 2.2 [ -1.3 to 5.8 ] , p=0.22 ) compared between the two groups at 4 weeks , as well as the VAS score ( 95 % CI,0.1 [ -0.3 to 0.6 ] , p=0.60 ) . Similar results presented at 8 and 12 weeks . No statistically significant difference was observed between CM and SM groups for outcome measurements . Conclusions It suggested that smoke generated during moxibustion treatment does not affect the efficacy of moxibustion in the treatment of KOA , which should be taken into account to be removed for the sake of reducing environmental pollution or moxa smoke exposure of acupuncturists or patients . This trial is registered with Clinical Trials.gov , NCT02772055 |
1,221 | 31,939,522 | CONCLUSIONS SRP has an impact on metabolic control and reduction of systemic inflammation of patients with T2D | OBJECTIVE The evidence is inconclusive regarding the effect of periodontal treatment on glycemic control and systemic inflammation in patients with type 2 diabetes ( T2D ) and periodontitis .
To evaluate the effect of scaling and root planing ( SRP ) on the metabolic control and systemic inflammation of patients with type 2 diabetes ( T2D ) . | Background There is a burglar association between diabetes and periodontitis . Many studies has shown that periodontitis treatment can help improving glycemic control in diabetes patients but little evidence of non-surgical treatment benefit is available in sub Saharan african diabetes patients . We aim ed to assess the effects of non-surgical periodontal treatment ( NSPT ) of chronic periodontitis on glycaemic control in poorly controlled type 2 diabetes patients ( T2D ) in a sub-Saharan Africa urban setting . Methods A total of 34 poorly controlled T2D patients with chronic periodontitis aged 51.4 ± 8.8 years ( mean ± SD ) , with known duration of diabetes of 55.5 ± 42.6 months , and HbA1c of 9.3 ± 1.3 % were r and omly assigned to two groups . The treatment group ( Group 1 , n = 17 ) received immediate ultrasonic scaling , scaling and root planning along with subgingival 10 % povidone iodine irrigation , whereas the control group ( Group 2 , n = 17 ) was assigned to receive delayed periodontal treatment 3 months later . Pharmacological treatment was unchanged and all participants received the same st and ardized education session on diabetes management and dental hygiene . The primary outcome was the 3-month change in HbA1c from baseline . Plaque index ( PI ) , gingival bleeding index ( GBI ) , pocket depth ( PD ) , clinical attachment loss ( CAL ) were also assessed prior to , at 6 and 12 weeks after enrolment . Results Two subjects in each group were excluded from the study . Data were analyzed on thirty patients ( 15 per group ) . Non-surgical periodontal treatment with education for better dental hygiene ( group 1 ) significantly improved all periodontal parameters whereas education only ( group 2 ) improved only the plaque index among all periodontal parameters . Immediate non-surgical periodontal treatment induced a reduction of HbA1c levels by 3.0 ± 2.4 points from 9.7 ± 1.6 % at baseline to 6.7 ± 2.0 % 3 months after NSPT , ( p ˂ 0.001 ) but the change was not significant in group 2 , from mean 8.9 ± 0.9 % at baseline vs 8.1 ± 2.6 % after 3 months ( p = 0.24 ) . Conclusion Non-surgical periodontal treatment markedly improved glycaemic control with an attributable reduction of 2.2 points of HbA1c in poorly controlled T2D patients in a sub Saharan setting .Trial registration Clinical Trials.gov Identifier : NCT02745015 Date of registration : July 17 , 2016 ‘ Retrospectively registered ’ BACKGROUND Cytokine dysregulation plays an important role in Type 2 Diabetes Mellitus ( T2DM ) and Chronic Periodontitis ( CP ) with a commonality in pathogenic mechanisms . CP is considered the sixth complication of diabetes and may have an increased influence on systemic levels of cytokines in individuals with T2DM . OBJECTIVE This study investigated two pro- , and two presumed anti-inflammatory cytokines and their ratios in the serum of healthy individuals , in chronic periodontitis with and without T2DM with , and without CP and in CP alone aim ed at evaluating the systemic inflammatory burden of a local oral infection . METHODS Eighty participants were divided equally into four groups as healthy volunteers ( H ) and patients having T2DM with , and without CP ( T2DM+CP , and T2DM ) and only CP ( CP ) . Serum sample s were collected to measure glycated hemoglobin ( HbA1c ) , R and om Blood Sugar ( RBS ) and also Tumor Necrosis Factor (TNF)-α , Interleukin (IL)-4 , -6 - 10 were assessed using commercially available ELISA kits . RESULTS The cytokines were detected in all groups . Significant differences were observed between groups for all the clinical , biochemical parameters and cytokines . Cytokine levels and the ratios showed significant correlations . The ratios of the cytokines differed significantly amongst groups , were highest in T2DM+CP . CONCLUSION In this study , the cytokine ratios provided a qualitative profile along with the absolute levels in T2DM with periodontitis , indicative of an intensified systemic inflammatory state OBJECTIVE To evaluate the effectiveness of community periodontal care intervention in type 2 diabetic patients with chronic periodontitis who participated in community non-communicable diseases management service . METHODS The r and omized controlled and blinded community trial with a duration of six months was design ed to compare effects of " periodontal initial therapy " on group I(22 cases ) , of " professional mechanical tooth cleaning ( PMTC ) , i.e. coronal scaling " on group II(19 cases ) and of " non- clinical therapy " on the control group(25 cases ) . The clinical periodontal indexes , such as probing depth ( PD ) , attachment loss ( AL ) , modified bleeding index ( mBI ) , plaque index ( PLI ) were obtained with a Williams type periodontal probe ; Laboratory examinations including glycosylated haemoglobin A1(HbA1C ) , glucose assay , were conducted . RESULTS The reductions of PD in groups I and II were 0.71 and 0.70 mm , respectively , which was more significant than in control group ( 0.20 mm ) ; the reductions of AL in groups I , II , and control group were 0.86 , 0.57 , and 0.03 mm , respectively , which showed significance in all the three groups . The subjects of groups I and II had 0.56 % and 1.01 % reductions of HbA1C respectively , and the significance was observed in group II . In addition , the improvement of HbA1C values in group II was highly correlated with the decrease in gingivitis ( r=0.51 , P=0.03 ) . CONCLUSION The community periodontal care approaches implemented in the community health service centers have significantly improved periodontal health as well as reduced glycemic level , which could be regarded as basic health care strategies for the patients with diabetes AIM The aim of this r and omized controlled clinical trial was to evaluate the clinical effects of chlorhexidine ( CHX ) application in a full-mouth disinfection ( FMD ) protocol in poorly controlled type-2 diabetic subjects with generalized chronic periodontitis . MATERIAL AND METHODS Thirty-eight subjects were r and omly assigned into FMD group ( n=19 ) : full-mouth scaling and root planing ( FMSRP ) within 24 h + local application of CHX gel + CHX rinses for 60 days or Control group ( n = 19 ) : FMSRP within 24 h + local application of placebo gel + placebo rinses for 60 days . Clinical parameters , glycated haemoglobin and fasting plasma glucose were assessed at baseline , 3 , 6 and 12 months post-therapies . RESULTS All clinical parameters improved significantly at 3 , 6 and 12 months post-therapies for both groups ( p < 0.05 ) . There were no significant differences between groups for any clinical parameters , and glycemic condition at any time-point ( p > 0.05 ) . CONCLUSIONS The treatments did not differ with respect to clinical parameters , including the primary outcome variable ( i.e. changes in clinical attachment level in deep pockets ) , for up to 12 months post-treatments Background 40 subjects with type 2 diabetes and moderate to severe CP were r and omly distributed to groups receiving either NSPT or OHI . Periodontal parameters , glycosylated haemoglobin ( HbA1c ) and high-sensitivity C-reactive protein ( hs-CRP ) were evaluated at baseline , 2- and 3-months intervals . Methods 40 subjects with type 2 diabetes and moderate to severe CP were r and omly distributed to groups receiving either NSPT or OHI . Periodontal parameters , glycosylated haemoglobin ( HbA1c ) and high-sensitivity C-reactive protein ( hs-CRP ) were evaluated at baseline , 2- and 3-months intervals . Results 15 subjects from NSPT group and 17 from OHI group completed the study . The difference in plaque index ( PI ) between NSPT and OHI groups were significant at 2 months recall ( p = 0.013 ) . There was no significant difference between NSPT and OHI group for all other clinical periodontal parameters , HbA1c and CRP levels . At 3 months post-therapy , periodontal parameters improved significantly in both groups with sites with probing pocket depth ( PPD ) < 4 mm reported as 98 ± 1.8 % in NSPT group and 92 ± 14.9 % in OHI group . Mean PPD and mean probing attachment loss ( PAL ) within the NSPT group reduced significantly from baseline ( 2.56 ± 0.57 mm , 3.35 ± 0.83 mm ) to final visit ( 1.94 ± 0.26 mm , 2.92 ± 0.72 mm ) ( p = 0.003 , p < 0.001 ) . For OHI group , improvements in mean PPD and mean PAL were also seen from baseline ( 2.29 ± 0.69 mm , 2.79 ± 0.96 mm ) to final visit ( 2.09 ± 0.72 mm , 2.62 ± 0.97 mm ) ( p < 0.001 for both ) . Similarly , HbA1c levels decreased in both groups with NSPT group recording statistically significant reduction ( p = 0.038 ) . Participants who demonstrated ≥ 50 % reduction in PPD showed significant reductions of HbA1c and hs-CRP levels ( p = 0.004 and p = 0.012 ) . Conclusion NSPT significantly reduced PI at 2 months post-therapy as compared to OHI . Both NSPT and OHI demonstrated improvements in other clinical parameters as well as HbA1c and CRP levels . Trial registration Clinical Trials.gov : NCT01951547 BACKGROUND AND OBJECTIVE Several studies have shown that periodontitis can complicate the severity of diabetes by worsening the degree of glycemic control . The purpose of this study was to determine the effect of full-mouth tooth extraction on glycemic control among type 2 diabetic patients . MATERIAL AND METHODS A total of 58 patients with type 2 diabetes mellitus and advanced periodontitis who were requiring extraction of all remaining teeth were r and omized consecutively into treatment ( full-mouth tooth extraction ) and control groups ( no treatment ) . Eight patients were lost to follow-up or reported use of antibiotics , leaving 50 patients to be included in the analysis . All patients had all their remaining teeth in a hopeless condition . Relevant data were collected , and glycosylated hemoglobin ( HbA(1c ) ) and fasting blood glucose levels were measured at baseline and at follow-up times of 3 and 6 mo . RESULTS At baseline , the mean ( SD ) HbA(1c ) level was 8.6 % ( 1.24 ) in the treatment group and 7.7 % ( 0.87 ) in the control group . In the treatment group , the mean HbA(1c ) level decreased significantly from 8.6 % at baseline to 7.4 % after 3 mo of denture treatment , and continued to decrease to 7.3 % after 6 mo . In the control group , the mean HbA(1c ) decreased from 7.7 % at baseline to 7.5 % after 3 mo , and remained almost the same after 6 mo . After adjusting for the baseline HbA(1c ) , the mean reduction in HbA(1c ) after 3 mo in the treatment group [ 1.23 % ( 0.79 ) ] was significantly higher than the mean reduction in the control group [ 0.28 % ( 0.87 ) ] . CONCLUSION Full-mouth tooth extraction result ed in an improvement in glycemic control among diabetic patients . Large-scale multicentre clinical trials are needed to confirm the current evidence 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 Patients with diabetes have a poor oral health-related quality of life ( OHRQoL ) . It is not clear if this situation could be changed with effective periodontal treatment . This study examined both patients with diabetes and systemically healthy individuals to discover the impact of a gingivitis treatment protocol on OHRQoL and its relation to objective periodontal parameters . DESIGN After ultrasonic debridement , patients were r and omly assigned to an essential-oils ( EO ) or placebo mouthwash group . At baseline and 3 months , OHRQoL was assessed with the Oral Health and Quality of Life-United Kingdom question naire ( OHQoL-UK ) along with clinical , halitometric , microbiological and inflammatory objective parameters . The primary outcome was a change in OHQoL-UK scores . A factor analysis was performed and the impact of the extracted quality of life factor ( QLF ) and its interactions with diabetes , treatment , and time on the objective parameters , were tested by multiple linear regression models ( p < 0.05 ) . Chi-Square test compared question naire-answering profiles ( p<0.05 ) . RESULTS Combined treatment with EO provided OHQoL improvements in both systemic conditions . Positive effect of oral health status on quality of life increased in EO groups but not in placebo groups . Question I ( self-confidence ) showed the greatest factorial weight , while Question A ( food intake ) showed the lowest factorial weight . All patients who showed OHRQoL improvements and used the EO rinse showed the lowest plaque and gingival indices and lower levels of bacteria and volatile sulfur compounds . CONCLUSIONS OHRQoL positively changed overtime . Most effective treatment protocol s would provide better improvements in OHRQoL which is related to periodontal objective measures BACKGROUND The present clinical trial was design ed to investigate the effectiveness of subgingivally delivered satranidazole ( SZ ) gel as an adjunct to scaling and root planing ( SRP ) in the treatment of chronic periodontitis . METHODS Sixty-four subjects with probing depth ( PD ) ≥ 5 mm and who were diagnosed with type 2 diabetes were selected . Thirty-two subjects each were r and omly assigned to SRP + placebo ( Group 1 ) and SRP + SZ ( Group 2 ) . The clinical outcomes evaluated were plaque index ( PI ) , gingival index ( GI ) , clinical attachment level ( CAL ) and PD at baseline , 1 month , 3-months and 6 months . RESULTS At 6 months , Group 2 had greater mean reduction ( 4.73 mm ) in PD as compared to Group 1 ( 2.09 mm ; p < 0.05 ) and also a greater mean CAL gain ( 3.92 mm versus 1.64 mm ; p < 0.05 ) . CONCLUSION The use of 3 % SZ gel , when used as an adjunct to non-surgical periodontal therapy in subjects with periodontitis , achieves significantly better clinical results than initial periodontal treatment alone In vitro and animal studies suggest a possible role for the tetracycline class of drugs in the inhibition of non-enzymatic protein glycation . We conducted a 3-month , r and omized placebo-controlled pilot clinical trial of conventional sub-gingival debridement ( periodontal therapy ) , combined with either a three month regimen of sub-antimicrobial-dose doxycycline ( SDD ) , a two week regimen of antimicrobial-dose doxycycline ( ADD ) , or placebo in 45 patients with long-st and ing type 2 diabetes ( mean duration 9 years ) and untreated chronic periodontitis . Subjects were taking stable doses of oral hypoglycemic medications and /or insulin . Treatment response was assessed by measuring hemoglobin A1c ( HbA1c ) , plasma glucose , and clinical periodontal disease measures . At one-month and three-month follow-up , clinical measures of periodontitis were decreased in all groups ( data to be presented elsewhere ) . At three months , mean HbA1c levels in the SDD group were reduced 0.9 % units from 7.2 % units±2.2 ( ±SD ) , to 6.3 % units±1.1 , which represents a 12.5 % improvement . In contrast , there was no significant change in HbA1c in the ADD ( 7.5%±2.0 to 7.8%±2.1 ) or placebo ( 8.5%±2.0 to 8.5%±2.6 ) groups . Mean HbA1c change from baseline was significantly greater in the SDD group compared with the ADD group ( p=0.04 ) but not placebo ( p=0.22 ) . Moreover , a larger proportion of subjects in the SDD group experienced improvement ( p<0.05 ) compared to the ADD or placebo groups . Mean plasma glucose levels were not significantly different between or within the groups . The results of this pilot study suggest that the treatment of periodontitis with sub-gingival debridement and 3-months of daily sub-antimicrobial-dose doxycycline may decrease HbA1c in patients with type 2 diabetes taking normally prescribed hypoglycemic agents AIM To evaluate the clinical , microbiological and immunological effects of systemic doxycycline as an adjunct to scaling and root planing ( SRP ) in chronic periodontitis patients with well-controlled type 2 diabetes . MATERIAL S AND METHODS Sixty-six patients compliant to oral hygiene ( Hygiene Index < 20 % ) allocated to either a test ( systemic doxycycline for 21 days ) or a control ( placebo ) group participated in the present r and omized controlled trial ( RCT ) . Clinical assessment s were recorded at baseline , 3 and 6 months after therapy and included clinical attachment level ( CAL ) , set as the primary outcome of the study , probing pocket depth ( PPD ) , recession ( RE ) and bleeding on probing ( BOP ) . At the same time points , counts of 15 subgingival species were evaluated by " checkerboard " DNA-DNA hybridization , gingival crevicular fluid sample s were analysed for matrix metalloproteinase-8 ( MMP-8 ) by ELISA and HbA1c levels were determined . Comparisons between and within groups were performed by non-parametric tests ( Mann-Whitney , Wilcoxon signed-ranks and z-test for proportions with Bonferroni corrections ) at the 0.05 level . RESULTS No major differences were noticed in clinical and microbiological parameters of periodontal disease or levels of MMP-8 between the two groups . CONCLUSIONS Adjunctive systemic doxycycline does not seem to significantly enhance the effects of SRP in well-controlled diabetes type 2 patients Background This study will assess measures of vascular health and inflammation in Aboriginal Australian adults with chronic kidney disease ( CKD ) , and determine if intensive periodontal intervention improves cardiovascular health , progression of renal disease and periodontal health over a 24-month follow-up . Methods The study will be a r and omised controlled trial . All participants will receive the periodontal intervention benefits , with the delayed intervention group receiving periodontal treatment 24 months following baseline . Inclusion criteria include being an Aboriginal Australian , having CKD ( a. on dialysis ; b. eGFR levels of < 60 mls/min/1.73 m2 ( CKD Stages 3 to 5 ) ; c. ACR ≥30 mg/mmol irrespective of eGFR ( CKD Stages 1 and 2 ) ; d. diabetes plus albuminuria ( ACR ≥ 3 mg/mmol ) irrespective of eGFR ) , having moderate or severe periodontal disease , having at least 12 teeth , and living in Central Australia for the 2-year study duration . The intervention involves intensive removal of dental plaque biofilms by scaling , root-planing and removal of teeth that can not be saved . The intervention will occur in three visits ; baseline , 3-month and 6-month follow-up . The primary outcome will be changes in carotid intima-media thickness ( cIMT ) . Secondary outcomes will include progression of CKD or death as a consequence of CKD/cardiovascular disease . Progression of CKD will be defined by time to the development of the first of : ( 1 ) new development of macroalbuminuria ; ( 2 ) 30 % loss of baseline eGFR ; ( 3 ) progression to end stage kidney disease defined by eGFR < 15 mLs/min/1.73 m2 ; ( 4 ) progression to end stage kidney disease defined by commencement of renal replacement therapy . A sample size of 472 is necessary to detect a difference in cIMT of 0.026 mm ( SD 0.09 ) at the significance criterion of 0.05 and a power of 0.80 . Allowing for 20 % attrition , 592 participants are necessary at baseline , rounded to 600 for convenience . Discussion This will be the first RCT evaluating the effect of periodontal therapy on progression of CKD and cardiovascular disease among Aboriginal patients with CKD . Demonstration of a significant attenuation of CKD progression and cardiovascular disease has the potential to inform clinicians of an important , new and widely available strategy for reducing CKD progression and cardiovascular disease for Australia ’s most disadvantaged population .Trial registration This trial is registered with the Australian New Zeal and Clinical Trial Registry ANZCTR12614001183673 Current evidence suggests that periodontal infection may aggravate diabetes control . The aim of this study was to determine the changes in the frequency with which Porphyromonas gingivalis , Tannerella forsythia , Treponema denticola and Aggregatibacter actinomycetemcomitans were detected in patients with diabetes with the use of non-surgical therapy plus azithromycin in a r and omized clinical trial . One hundred and five ( 105 ) patients with diabetes and chronic periodontitis were r and omly assigned to three treatment groups : subgingival mechanical therapy with azithromycin , subgingival mechanical therapy with placebo and supragingival prophylaxis with azithromycin . Complete periodontal clinical examinations and detection of periodontal pathogens using polymerase chain reaction were carried out at baseline , 3 , 6 and 9 months after periodontal therapy . The frequency with which Porphyromonas gingivalis , Treponemadenticola and Aggregatibacter actinomycetemcomitans were detected decreased at 3 months in all groups . Tannerella forsythia increased after3 months in all groups . All organisms had similar frequencies at 9 months in all groups . Subgingival mechanical therapy with adjunctive azithromycin had no additional effect on the frequency with which the periodontal pathogens investigated were detected in patients with diabetes Studies indicate that a dual pathway between diabetes mellitus and periodontal disease exists . Elimination of periodontal infection by using systemic antibiotics in conjunction with scaling and root planing ( SRP ) improved metabolic control in diabetic patients , as defined by reduction in glycated haemoglobin or reduction in insulin requirements ( Grossi and Genco , 1998 ) . The aim of this r and omised pilot clinical trial was to determine if type 1 diabetes patients with periodontitis will experience a reduction in HbA1c levels when treated with locally delivered minocycline microspheres ( Arestin ) as an adjunct to scaling and root planing . Twenty adult patients with poorly controlled diabetes ( HbA1c 7.5 % ) and adult periodontitis , as determined by the presence of four teeth with 5 mm periodontal pockets , two of which had 6 - 9 mm pockets and bleeding on probing , were included in the study . All patients received full mouth SRP at baseline . Arestin was administered to all pockets > or = > or = 5 mm at baseline and again at 12 weeks in the test group . Probing depth ( PD ) , clinical attachment level ( CAL ) , plaque index ( PI ) , gingival index ( GI ) , and HbA1c were evaluated at baseline and at weeks 6 , 12 , 18 and 24 . The results demonstrated that local administration of Arestin as an adjunct to scaling and root planing is significantly more effective in reducing probing depths and providing a gain in clinical attachment levels than scaling and root planing alone in type 1 diabetic patients . Hb1Ac was reduced in all patients ; however the difference between the test and control groups was not significant OBJECTIVE To investigate the effectiveness of short-term adjunctive subantimicrobial dose doxycycline ( SDD ) treatment in patients with diabetes mellitus type 2 and chronic periodontitis ( CP ) . METHODS Thirty-four patients with CP and type 2 diabetes mellitus were included in the placebo-controlled , double-blind study . After scaling and root planing ( SRP ) , patients were r and omly assigned to two groups , receiving either SDD or placebo bid for 3 months . The probing depth ( PD ) , clinical attachment level ( CAL ) , bleeding on probing ( BOP ) , approximal plaque index , glycated hemoglobin ( HbA1c ) level were recorded and gingival crevicular fluid ( GCF ) sample s were collected at baseline and after 3-month therapy for the estimation of matrix metalloproteinase-8 levels . RESULTS Clinical attachment level , PD , and BOP improved significantly in both groups after therapy ( P < 0.05 ) . The statistically significant difference between the two groups after the therapy was observed only in PD in tooth sites with initial PD ≥ 4 mm ( SRP + placebo : 3.41 ± 0.6 mm vs SRP + SDD : 2.92 ± 0.5 mm , P < 0.05 ) . GCF matrix metalloproteinase-8 levels were significantly reduced only in SRP + SDD group ( P < 0.01 ) . There were no changes in HbA1c levels after therapy . CONCLUSION The short-term administration of SDD gives significant benefit at tooth sites with moderate disease ( PD ≥ 4 mm ) when compared to SRP alone in patients with diabetes and CP Periodontal disease is a common infection-induced inflammatory disease among individuals suffering from diabetes mellitus . The purpose of this study was to assess the effects of treatment of periodontal disease on the level of metabolic control of diabetes . A total of 113 Native Americans ( 81 females and 32 males ) suffering from periodontal disease and non-insulin dependent diabetes mellitus ( NIDDM ) were r and omized into 5 treatment groups . Periodontal treatment included ultrasonic scaling and curettage combined with one of the following antimicrobial regimens : 1 ) topical water and systemic doxycycline , 100 mg for 2 weeks ; 2 ) topical 0.12 % chlorhexidine ( CHX ) and systemic doxycycline , 100 mg for 2 weeks ; 3 ) topical povidone-iodine and systemic doxycycline , 100 mg for 2 weeks ; 4 ) topical 0.12 % CHX and placebo ; and 5 ) topical water and placebo ( control group ) . Assessment s were performed prior to and at 3 and 6 months after treatment and included probing depth ( PD ) , clinical attachment level ( CAL ) , detection of Porphyromonas gingivalis in subgingival plaque and determination of serum glucose and glycated hemoglobin ( HbA1c ) . After treatment all study groups showed clinical and microbial improvement . The doxycycline-treated groups showed the greatest reduction in probing depth and subgingival Porphyromonas gingivalis compared to the control group . In addition , all 3 groups receiving systemic doxycycline showed , at 3 months , significant reductions ( P < or = 0.04 ) in mean HbA1c reaching nearly 10 % from the pretreatment value . Effective treatment of periodontal infection and reduction of periodontal inflammation is associated with a reduction in level of glycated hemoglobin . Control of periodontal infections should thus be an important part of the overall management of diabetes mellitus patients BACKGROUND Herbal agents such as Aloe vera ( AV ) have been used in medical and dental therapy for thous and s of years . AV has anti-inflammatory , antioxidant , antimicrobial , hypoglycemic , healing-promoting , and immune-boosting properties . This study aims to investigate the clinical effectiveness of locally delivered AV gel used as an adjunct to scaling and root planing ( SRP ) in the treatment of patients with type 2 diabetes mellitus ( T2DM ) and chronic periodontitis ( CP ) . METHODS Sixty patients with probing depth ( PD ) ≥ 5 mm and clinical attachment level ( CAL ) ≥ 3 mm were r and omly divided into two groups . All patients underwent SRP . Placebo gel was locally delivered to group 1 and AV gel to group 2 . Full-mouth plaque index ( PI ) , modified sulcus bleeding index ( mSBI ) , PD , and CAL were recorded at baseline and 3 and 6 months . RESULTS Patients in group 2 showed significantly greater mean reductions in PI , mSBI , and PD and mean gain in CAL compared with those in group 1 from baseline to 3 months . Gain in CAL was significantly greater in group 2 at all time intervals versus group 1 . CONCLUSION Adjunctive use of locally delivered AV gel , in comparison to locally delivered placebo gel , is associated with greater reduction in PI , mSBI , and PD as well as more gain in CAL in patients with T2DM and CP AIMS : The purpose of this study is to investigate the effect of improved periodontal health on glycemic control in type 2 diabetes mellitus ( type 2 DM ) patients who have generalized periodontitis . MATERIAL S AND METHODS : A total of 45 type 2 DM patients with generalized periodontitis were selected for the study . The selected patients were r and omly assigned to three groups ( groups A , B , and C ) comprising 15 patients each : • Group A received treatment with scaling and root planing only . • Group B received treatment with scaling and root planing followed by systemic doxycycline . • Group C received no treatment ( control group ) . The periodontal parameters recorded included plaque index , gingival index , probing pocket depth , and clinical attachment level . These parameters were recorded at baseline ( day zero ) , at 1 month , and at the end of 3 months . The following metabolic parameters were recorded : fasting blood glucose ( FBG ) , postpr and ial blood glucose ( PPBG ) , and glycated hemoglobin . These were recorded at baseline ( day zero ) and at the end of 3 months . STATISTICAL ANALYSIS : All the parameters were subjected to repeated- measures ANOVA and Scheffe 's post hoc test . RESULTS : A statistically significant effect could be demonstrated for periodontal parameters for both group A and group B ( treatment groups ) . Glycated hemoglobin values showed statistically significant decrease in treatment groups compared to the control group , with group B showing more significant decrease than group A. CONCLUSIONS : The results of this study showed that nonsurgical periodontal treatment is associated with improved glycemic control in type 2 DM patients BACKGROUND Periodontitis is a major cause of tooth loss among adults . Several studies have shown a possible systemic impact of periodontal infection , including poor glycemic control in patients with diabetes . Recently , photodynamic therapy ( PDT ) was used to successfully treat periodontal infection . PDT provides a broad spectrum antimicrobial efficacy with no local or systemic side effects . The objective of this study was to examine the effect of the adjunctive use of PDT on periodontal status and glycemic control of patients with diabetes and periodontitis . METHODS Forty-five patients with type 2 diabetes and moderate to severe chronic periodontitis were selected and r and omly assigned to one of the following three treatment modalities ( 15 subjects each ) : scaling and root planing ( SRP ) only , SRP plus systemic doxycycline , and SRP plus PDT . The plaque and bleeding scores , probing depth , clinical attachment level , and glycosylated hemoglobin ( HbA1c ) level were recorded at baseline and 3 months after periodontal treatment . Descriptive statistics , the paired t test , and analysis of variance ( ANOVA ) were used for data analysis . RESULTS Statistically significant differences in the mean probing depth , clinical attachment level , plaque deposit , and bleeding on probing were found between baseline and 12 weeks post-treatment for all groups . No significant differences in periodontal parameters and glucose levels were detected among the three groups . Reduction in the mean HbA1c level after treatment was observed in all groups but was only significant for the SRP plus doxycycline group . CONCLUSION The results of the present study indicate that PDT does not benefit conventional non-surgical periodontal therapy in patients with diabetes BACKGROUND / AIM There is clear evidence on direct relationship between periodontal disease and diabetes mellitus . Many investigations point out greater prevalence and severity of periodontal disease among diabetic patients . During last decade , low level laser therapy has been used in periodontal therapy . It has biostimulative effect , accelerates wound healing , minimizes pain and swelling , and there is almost no contraindication for its usage . The aim of the paper was to investigate the efficiency of low level laser therapy as adjuvant tool in reduction of gingival inflammation in diabetic patients . METHODS The study incuded 150 participants divided into three groups : group I ( 50 participants with diabetes mellitus type 1 and periodontal disease ) , group II ( 50 participants with diabetes mellitus type 2 and periodontal disease ) , group III ( nondiabetic participants with periodontal disease ) . Gingival health evaluation was done using gingival index Löe-Silness . Soft and hard deposits were removed , periodontal pockets cleaned and GaA1As low level laser therapy ( 5 mW ) applied five consecutive days . In each patient , low level laser therapy was not applied on the left side of the jaw in order to compare the effects of the applied therapy . After the first , third and fifth therapy and one month after the last visit gingival index was evaluated . Before the first and after the fifth therapy exfoliative cytology of gingiva was done and nuclei areal was analyzed morphometrically . RESULTS After all investigated periods , gingival index and nuclei areal were significantly decreased comparing to values before the therapy , at both jaw sides ( p < 0.001 ) . After the 1st , 3rd and 5th therapy , the t-test showed a significantly decreased gingival index at the lased side of jaw comparing to non-lased side . CONCLUSION Low level laser therapy is efficient in gingival inflammation elimination and can be proposed as an adjuvant tool in basic periodontal therapy of diabetic patients AIM The primary aim of this study was to examine the effects of intensive periodontal therapy on HbA(1c ) in a mixed diabetes mellitus ( DM ) ( types 1 and 2 ) population with moderate periodontitis ( PD ) . METHODS A total of 93 subjects with PD and DM , recruited from referrals to the Department of Endocrinology at the Perugia Hospital , were included in a follow-up cohort clinical study comprising two parallel periodontal therapy groups-one receiving intensive periodontal therapy ( IPT , n=44 ) and the other serving as controls ( CPT , n=49)-with an 8-month follow-up . Clinical periodontal examinations and blood sample s were collected 4 and 8 months after the completion of therapy . RESULTS The IPT group presented with greater reductions of all periodontal indices compared with the CPT group at both follow-ups ( P<0.001 ) . Whereas , after 4 months , there were no major differences in HbA(1c ) levels between groups , after 8 months , the IPT group presented with a 0.57 % ( 95 % CI : 0.12 to 1.09 ) greater reduction in HbA(1c ) than the CPT group ( P=0.03 ) . This reduction was independent of age , gender , smoking and body mass index . However , the difference in HbA(1c ) was greater in individuals with type 2 DM ( 0.95 % reduction , 95 % CI : 0.32 to 1.58 ; P=0.004 ) compared with those with type 1 DM . CONCLUSION IPT result ed in greater improvement of gingival health in patients with DM . Improved oral health in those with type 2 DM may have an effect on medium-term glucose management and could possibly lead to long-term health benefits . ( IS RCT N00559156 ) BACKGROUND Propolis is a natural resin made by bees from various plant sources and exerts antimicrobial , anti-inflammatory , immunomodulatory , antioxidant , and antidiabetic properties . The purpose of this study is to assess adjunctive benefit of propolis supplementation in individuals with chronic periodontitis ( CP ) and type 2 diabetes mellitus ( DMt2 ) receiving scaling and root planing ( SRP ) . METHODS A 6-month masked , r and omized clinical trial comparing SRP with placebo ( placebo + SRP group , n = 26 ) or SRP combined with a 6-month regimen of 400 mg oral propolis once daily ( propolis + SRP group , n = 24 ) was performed in patients with long-st and ing DMt2 and CP . Treatment outcomes included changes in hemoglobin ( Hb ) A1c ( primary outcome ) , fasting plasma glucose ( FPG ) , serum N€-(carboxymethyl ) lysine ( CML ) , and periodontal parameters ( secondary outcomes ) . RESULTS After 3 and 6 months , average HbA1c levels in the propolis group decreased significantly by 0.82 % and 0.96 % units , respectively ( P < 0.01 ) ; however , there were no significant differences in the placebo group . Likewise , FPG and CML levels were significantly reduced in the propolis group , but not in the placebo group . After therapy , periodontal parameters of CP were significantly improved in both groups . The propolis group showed significantly greater probing depth reduction and clinical attachment level gain than the control group after 3 and 6 months . CONCLUSION A 6-month regimen of 400 mg propolis once daily is a potentially viable adjunct to SRP that significantly reduces levels of HbA1c , FPG , and CML , and improves periodontal therapy outcome in people with DMt2 and CP AIM the purpose of the present study was to assess the effect of non-surgical periodontal therapy on glycaemic control of type 2 diabetes patients with moderate-to-severe periodontitis . MATERIAL S AND METHODS this was a r and omized , controlled clinical trial of patients with type 2 diabetes . A total of 60 patients with moderate-to-severe periodontal disease were assigned to either a periodontal treatment arm , consisting of scaling and root planing ( intervention group [ IG ] ) , or a delayed treatment arm that received periodontal care after 6 months ( control group [ CG ] ) . Periodontal parameters and glycosylated haemoglobin ( A1C ) were evaluated at 1 , 3 and 6 months . RESULTS all periodontal parameters improved significantly in the IG . A1C levels decreased statistically significantly more in the IG versus the CG ( 0.72%versus 0.13 % ; p<0.01 ) independently of other confounders . CONCLUSIONS this study provides evidence that periodontal treatment contributes to improved glycaemic control in type 2 diabetes mellitus patients . Larger controlled trials are needed to confirm if this finding is generalizable to other population s of patients with type 2 diabetes Aim The purpose of this study was to investigate the effects of non-surgical periodontal treatment on hemoglobinA1c ( HbA1c ) levels , oxidative stress balance and quality of life ( QOL ) in patients with type 2 diabetes mellitus ( T2DM ) compared to no periodontal treatment ( simple oral hygiene instructions only ) . Methods The design was a 6-month , single-masked , single center , r and omized clinical trial . Patients had both T2DM and chronic periodontitis . Forty participants were enrolled between April 2014 and March 2016 at the Nephrology , Diabetology and Endocrinology Department of Okayama University Hospital . The periodontal treatment group ( n = 20 ) received non-surgical periodontal therapy , including scaling and root planing plus oral hygiene instructions , and consecutive supportive periodontal therapy at 3 and 6 months . The control group ( n = 17 ) received only oral hygiene instructions without treatment during the experimental period . The primary study outcome was the change in HbA1c levels from baseline to 3 months . Secondary outcomes included changes in oxidative stress balance ( Oxidative-INDEX ) , the Diabetes Therapy-Related QOL and clinical periodontal parameters from baseline to 3 months and baseline to 6 months . Results Changes in HbA1c in the periodontal treatment group were not significantly different with those in the control group at 3 and 6 months . Systemic oxidative stress balance and QOL significantly improved in the periodontal treatment group compared to the control group at 3 months . In the subgroup analysis ( moderately poor control of diabetes ) , the decrease in HbA1c levels in the periodontal treatment group was greater than that in the control group at 3 months but not significant . Conclusions In T2DM patients , non-surgical periodontal treatment improved systemic oxidative stress balance and QOL , but did not decrease HbA1c levels at 3 months follow-up . Trial registration Current Controlled Trials UMIN-ICDR UMIN 000013278 ( Registered April 1 , 2014 ) Diabetic patients are more prone to develop infections such as periodontal diseases . Bacteriotherapy with the concept of using good bacterial strains to replace the pathogenic ones emerged as a fascinating field due to the increasing incidence of antibiotic resistance . The aim of this study was to evaluate if a particular combination of probiotics ( Lactobacillus Reuteri DSM 17938 and Lactobaciullus Reuteri ATCC PTA 5289 ) is useful in treating gingivitis in diabetic patients . Eighty adult patients with diagnosis of controlled diabetes type II and gingivitis were enrolled for this study and r and omized in two groups . Only oral hygiene instructions were given . Bacteriotherapy ( Lactobacillus Reuteri ) was administered to test group . Outcome measures were presence of Plaque ( P.I. ) and Bleeding on Probing ( B.O.P. ) . Data were collected at baseline and after 30 days . At 30 days , both groups showed a statistically significant clinical indexes reduction from baseline . More reduction was present in the test group for P.I. ( 14%±6 ) and for B.O.P. ( 18%±4 ) and was statistically significant ( p less than 0.05 ) . Within the limitations of this study , bacteriotherapy can be considered effective in reducing plaque and BOP in patients with controlled diabetes type II and gingivitis BACKGROUND Simplified periodontal therapy might be a pragmatic strategy for public health programmes targeting Indigenous Australian adults . The objective of this r and omized controlled trial was to evaluate oral health effects of single-visit , non-surgical periodontal therapy compared to no treatment . METHODS This parallel-group , r and omized , open label clinical trial enrolled 273 Indigenous Australians aged ≥18 years with periodontitis . Intervention participants received full-mouth periodontal scaling and root planing during a single visit while the control group received no treatment . Endpoints were summary variables derived from clinical assessment s of probing depth , clinical attachment loss , plaque , calculus and gingival bleeding before treatment and 3 months later . RESULTS Endpoints could be calculated for 169 participants with follow-up data . Compared to the control group , there were statistically significant reductions in extent of shallow pockets : PD ≥4 mm ( mean difference -2.86 , [ 95 % CI -5.01 to -0.71 ] , p = 0.009 ) and gingival bleeding ( mean difference -0.25 , [ 95 % CI -0.43 to -0.08 ] , p = 0.005 ) but not deeper pockets PD ≥5 mm ( mean difference -0.48 , [ 95 % CI -1.78 to 0.82 ] , p = 0.468 ) or plaque scores . CONCLUSIONS Periodontal therapy produced improvements in shallow periodontal pockets and measures of gingival bleeding in these Indigenous Australians UNLABELLED The AIM of this study was to evaluate the effect of non-surgical therapy on clinical variables and glycemic control on type 2 diabetics with chronic periodontitis . PATIENTS AND METHODS Forty six type 2 diabetics with chronic periodontitis were r and omized into two groups ( group A and group B ) . Treatment included scaling and root planning for group A plus systematic use of doxycycline in both groups . Assessment was made prior to and 16 weeks following the therapy . RESULTS Analysis of data showed that both groups had clinical and glycated hemoglobin ( HbAlc ) improvement after the treatment . Group A had a statistically significant reduction of plaque index and bleeding on probing scores compared with controls ( P < 0.05 ) at 16 weeks . CONCLUSION These results suggest that non-surgical therapy is of value in maintaining periodontal health and may be beneficial in reducing blood glucose level in type 2 diabetics with chronic periodontitis BACKGROUND The literature suggests that an alteration in glucose metabolism occurs as a result of antibacterial periodontal therapy . The objective of this study was to monitor the effect of non-surgical periodontal therapy on glycemic control in patients with type 2 diabetes mellitus ( DM ) . METHODS Thirty type 2 DM subjects with periodontitis were r and omly divided into two groups . Group 1 ( G1 ) , 15 subjects , received one-stage full-mouth scaling and root planing ( FMSRP ) plus amoxicillin/clavulanic acid 875 mg ; group 2 ( G2 ) , 15 patients , received only FMSRP . At baseline and after 3 months , the glycated hemoglobin ( HbA1c ) values , fasting glucose , and clinical parameters ( with computerized probing and individualized acrylic stents ) were recorded . Following therapy , the subjects were enrolled in a 2-week interval maintenance program for 3 months . RESULTS After treatment , both groups showed clinical improvements . A probing depth ( PD ) reduction of 0.8 + /- 0.6 mm ( P < 0.05 ) occurred in G1 and 0.9 + /- 0.4 mm in G2 ( P < 0.05 ) , but there were no significant changes in attachment level . Treatment reduced the HbA1c values after the 3-month observation period in both groups ; however , the reduction in HbA1c values for the G2 group was statistically significant , but not for the G1 group . The changes in fasting glucose levels were not significant for either group . CONCLUSIONS Periodontal therapy improved glycemic control in patients with type 2 DM in both groups ; however , the reduction in HbA1c values reached statistical significance only in the group receiving scaling and root planing alone [ correction ] We evaluated the effects of nonsurgical periodontal therapy in 100 patients with type 2 diabetes and chronic periodontitis . The participants were classified as having good ( n = 48 ) or poor ( n = 52 ) glycemic control and were further r and omly allocated to receive either scaling and root planning treatment group or no treatment ( n = 50 each ) . The effect of nonsurgical periodontal therapy was compared among diabetic patients with good glycemic control , those with poor glycemic control , and 25 nondiabetic individuals . Periodontal and metabolic status was recorded at baseline , 3 months , and 6 months . In patients receiving treatment , periodontal parameters significantly improved and HbA1c decreased by 10.8 % . Improvements in gingival index and bleeding on probing were greater in the nondiabetic participants and the treated patients with good glycemic control than in the treated patients with poor glycemic control ( P < 0.05 ) . Regression analysis showed that improvement in periodontal status was independently associated with glycemic improvement . Nonsurgical periodontal therapy improved glycemic control and periodontal health in patients with type 2 diabetes . However , patients with poor baseline glycemic control had less clinical improvement than did those without diabetes and those with good glycemic control The aim of this study was to assess the changes occurring in subgingival biofilm composition and in the periodontal clinical parameters of subjects with periodontitis and type 2 diabetes mellitus ( DM ) treated by means of scaling and root planing ( SRP ) only or combined with systemic metronidazole ( MTZ ) and amoxicillin ( AMX ) . Fifty-eight subjects were r and omly assigned to receive SRP only ( n = 29 ) or with MTZ ( 400 mg/thrice a day [ TID ] ) and AMX ( 500 mg/TID ) ( n = 29 ) for 14 d. Six subgingival plaque sample s/subject were analyzed by checkerboard DNA – DNA hybridization for 40 bacterial species at baseline and 3 mo , 1 y , and 2 y posttherapy . At 2 y posttherapy , the antibiotic-treated group harbored lower mean proportions ( 5.5 % ) of red complex pathogens than the control group ( 12.1 % ) ( P < 0.05 ) . The proportions of the Actinomyces species remained stable in the antibiotic group but showed a statistically significant reduction in the control group from 1 to 2 y in subjects achieving a low risk clinical profile for future disease progression ( i.e. , ≤4 sites with probing depth [ PD ] ≥5 mm ) . The test group also had a lower mean number of sites with PD ≥5 mm ( 3.5 ± 3.4 ) and a higher percentage of subjects reaching the low risk clinical profile ( 76 % ) than the control group ( 14.7 ± 13.1 and 22 % , respectively ) ( P < 0.05 ) at 2 y posttreatment . MTZ + AMX intake was the only significant predictor of subjects achieving the low risk at 2 y ( odds ratio , 20.9 ; P = 0.0000 ) . In conclusion , the results of this study showed that the adjunctive use of MTZ + AMX improves the microbiological and clinical outcomes of SRP in the treatment of subjects with generalized chronic periodontitis and type 2 DM up to 2 y ( Clinical Trials.gov NCT02135952 ) AIM The aim of the present study was to assess the effectiveness of mechanical debridement ( MD ) with and without adjunct antimicrobial photodynamic therapy ( aPDT ) in the treatment of periodontal inflammation among patients with prediabetes . METHODS Demographic information was collected using a question naire . Hemoglobin A1c ( HbA1c ) levels were measured at baseline and at 3 and 6 months ' follow-up . TREATMENT Individuals were r and omly divided into 2 groups as follows : ( a ) Group-1 , participants underwent full-mouth MD ; and Group-2 : participants underwent full-mouth MD with adjunct aPDT . In groups 1 and 2 , full-mouth plaque index ( PI ) , bleeding on probing ( BOP ) and probing pocket depth ( PPD ) were measured at baseline and at 3 and 6 months ' follow-up . In both groups , full-mouth digital intraoral radiographs were also taken . Sample -size was estimated and statistical analysis was performed with level of significance set as P<0.05 . RESULTS In total , 70 prediabetic male individuals ( 35 patients in group-1 and 35 in group-2 ) were included . At baseline , PI , BOP , number of sites with PPD ≥4 mm were comparable among individuals in groups 1 and 2 . In groups 1 and 2 , PI ( P<0.05 ) , BOP ( P<0.05 ) , number of sites with PPD ≥4 mm ( P<0.05 ) were significantly higher at baseline compared with 3 months ' follow-up . There was no statistically significant difference in PI , BOP , number of sites with PPD ≥4 mm at 3 and 6 months ' follow-up . At 6 months ' follow-up , PI , BOP , number of sites with PPD ≥4 mm were comparable to their respective baseline values . There was no statistically significant difference in CBL in both groups at 3 and 6 months ' follow-up . There was no statistically significant difference in HbA1c levels among individuals in groups 1 and 2 at all-time intervals . CONCLUSION In the short-term , MD is effective in reducing periodontal inflammation among patients with prediabetes . The contribution of adjunct aPDT in this regard is insignificant BACKGROUND Triclosan toothpaste is effective in controlling plaque and gingivitis and slowing progression of periodontitis ; however , its influence on inflammatory biomarkers of cardiovascular disease ( CVD ) , as well as on kidney and liver function , is unknown . METHODS Patients recruited from the Cardiovascular Unit at Prince Charles Hospital , Brisbane , Australia , were r and omized to triclosan ( n = 193 ) or placebo ( n = 190 ) groups and assessed for total cholesterol ( TC ) , high density lipoprotein ( HDL ) and low density lipoprotein ( LDL ) cholesterol , triglycerides , C-reactive protein , erythrocyte sedimentation rate ( ESR ) , hemoglobin , total white cell count ( WCC ) , estimated glomerular filtration rate ( eGFR ) , and liver function enzymes , annually for 5 years . A st and ard mixed model for each marker included group , sex , age , hypertension , diabetes , periodontal status , statin and anti-inflammatory drug use , and smoking as covariates . Changes in eGFR , WCC , and ESR were further analyzed using transition modeling . RESULTS Triclosan toothpaste led to a greater decrease in TC ( P = 0.03 ) , LDL cholesterol ( P = 0.04 ) , and HDL cholesterol ( P = 0.05 ) than placebo toothpaste . ESR increased at a slower rate in the triclosan group ( P ≈ 0.06 ) and was less likely to increase and more likely to improve in males on statins but not anti-inflammatory drugs in the triclosan group versus the placebo group . Markov modeling of the binary response for eGFR ( greater than or less than/equal to the baseline median value ) showed that patients with diabetes in the placebo group were significantly ( P ≈ 0.05 ) more likely to deteriorate than either patients with diabetes in the triclosan group or patients without diabetes in each group . CONCLUSIONS These data suggest that triclosan toothpaste may influence some inflammatory biomarkers of CVD , but not kidney or liver function . However , it is unclear if this influence is clinical ly significant There is scarce evidence on suitable approaches for the treatment of unresponsive or residual periodontal sites in diabetic patients . This study assessed the effects of surgical debridement ( SD ) and nonsurgical debridement ( NSD ) , associated with amoxicillin and metronidazole , on clinical and immunological outcomes of residual pockets and adjacent healthy sites in patients with type 2 diabetes . A split-mouth , r and omized controlled trial was conducted in 21 patients presenting at least 2 residual pockets in contralateral quadrants 12 months after basic nonsurgical periodontal therapy . Patients received systemic antibiotics , and contralateral quadrants were assigned to receive SD or NSD . The changes in clinical parameters were evaluated from baseline to 12 months . Local levels of 14 cytokines and chemokines were measured with multiplex bead immunoassays at baseline and 3 and 12 months after therapy . There were no statistically significant differences between SD and NSD for changes in clinical parameters from baseline to 12 months ( P > 0.05 ) . There was a significantly greater increase in the levels of granulocyte-macrophage colony-stimulating factor and interleukin 6 from baseline to 3 months in the healthy sites adjacent to residual pockets receiving SD ( P < 0.05 ) . A significant decrease in the levels of monocyte chemoattractant protein-1 and macrophage inflammatory protein 1α occurred from baseline to 12 months in the residual pockets treated by SD ( P < 0.05 ) . In conclusion , SD and NSD result ed in similar clinical benefits at 12 months . The short-term increase in the levels of proinflammatory biomarkers in SD sites probably can be attributed to tissue trauma and healing , and the long-term decrease in the levels of chemotactic factors in residual pockets treated by surgery may reflect remission of infection and stable wound healing in these sites at 12 months AIM To evaluate the impact of two non-surgical periodontal treatment modalities on metabolic and periodontal clinical parameters in subjects with type 2 diabetes mellitus ( T2DM ) and poor glycaemic control and chronic periodontitis . MATERIAL AND METHODS A r and omized controlled clinical trial was conducted . Ninety-three T2DM subjects with glycosylated haemoglobin ( HbA1c ) > 7 % were r and omly assigned to one of two groups receiving scaling with root planing in multiple sessions quadrant-by-quadrant ( Q by Q ) or within 24 hr ( one stage ) . Periodontal parameters , HbA1c , glycaemia blood levels ( FPG ) and C-reactive protein ( CRP ) values were assessed at baseline and at 3 and 6 months post-therapy . RESULTS At 6 months , HbA1c had decreased by 0.48 % in the Q by Q group and by 0.18 % in the one-stage group ( p = 0.455 ) . After therapy , subjects with an initial HbA1c < 9 % showed an increase of 0.31 % ( p = 0.145 ) , compared with a decrease of 0.88 % ( p = 0.006 ) in those with an initial HbA1c ≥ 9 % . Periodontal parameters improved significantly ( p < 0.0001 ) post-therapy , with similar results for both treatment modalities . CONCLUSION Periodontal therapy had the greatest impact on HbA1c reduction on patients with an HbA1c > 9 % regardless of treatment modality . Both modalities result ed in significant improvements in periodontal parameters OBJECTIVE In the Mexican-American population , the prevalence of Type 2 diabetes mellitus ( T2DM ) is as high as 50 % of the population . This r and omized controlled clinical trial was design ed to eluci date how treatment of periodontal disease affects HbA1c values in this population . MATERIAL S AND METHODS One hundred and fifty-four T2DM patients with periodontal disease were enrolled in the study . The test group was treated with scaling and root planing ( SRP ) ; the control group received oral hygiene instructions . At baseline and 4 - 6 weeks after therapy , a complete periodontal examination was performed . Blood was collected at baseline and 4 months later for HbA1c levels . RESULTS One hundred and twenty-six individuals completed the study . Baseline mean ± SD HbA1c for the test and control groups were 9.0 ± 2.3 % and 8.4 ± 2.0 % respectively . Non-significant difference in HbA1c reductions ( 0.6 ± 2.1 % and 0.3 ± 1.7 % ) was found between test and control groups at 4 months . Comparisons of the periodontal clinical parameters between the test and control groups found significant differences with improved results in the test subjects . CONCLUSIONS No statistically significant differences were found in the changes of HbA1c levels between test and control groups . Non-surgical periodontal therapy improved the magnitude of change in periodontal parameters as compared to the control subjects . Clinical Trials.gov Identifier : NCT01128374 AIM To evaluate the clinical and microbiological effects of the use of metronidazole ( MTZ ) + amoxicillin ( AMX ) as adjuncts to scaling and root planing ( SRP ) for the treatment of chronic periodontitis ( ChP ) in type 2 diabetic subjects . MATERIAL AND METHODS Fifty-eight type 2 diabetic subjects ( n = 29/group ) with generalized ChP were r and omly assigned to receive SRP alone or with MTZ [ 400 mg/thrice a day (TID)]+AMX ( 500 mg/TID ) for 14 days . Subgingival biofilm sample s were analyzed by qPCR for the presence of seven periodontal pathogens . Subjects were monitored at baseline , 3 , 6 and 12 months post-therapies . RESULTS The group receiving SRP+MTZ+AMX presented greater mean probing depth ( PD ) reduction and clinical attachment gain , a lower number of sites with PD ≥5 mm ( primary outcome variable ) and a reduced number of subjects with ≥9 of these residual pockets than the control group at 1-year post-therapy ( p < 0.05 ) . The antibiotic-treated group also presented reduced levels and greater decreases of the three red complex species , Eubacterium nodatum and Prevotella intermedia , compared to the control group at 1 year ( p < 0.05 ) . CONCLUSIONS The adjunctive use of MTZ+AMX significantly improved the clinical and microbiological outcomes of SRP in the treatment of type 2 diabetic subjects with |
1,222 | 23,861,151 | Overall , most studies reported a significant improvement in symptom scores , decrease in corticosteroid use , and decrease in revision surgery .
Unlike traditional treatments for nasal polyposis , aspirin desensitization targets AERD etiology rather than phenotype and can be an effective therapeutic option . | OBJECTIVES To critically review the current literature regarding aspirin desensitization treatment for nasal polyposis in patients with Aspirin-Exacerbated Respiratory Disease ( AERD ) . | Background : The daily dose of aspirin in desensitization in aspirin‐sensitive asthmatics with nasal polyps is still a matter of debate INTRODUCTION Nasal polyposis associated with aspirin-intolerant asthma tends to be difficult to control , with frequent recurrences . We examined the effect of intranasal lysine-aspirin administration on resistant nasal polyps of asthmatic , aspirin-intolerant patients , when used in addition to routine therapy . PATIENTS AND METHODS Thirteen patients with asthma and intolerance to aspirin were recruited . All but one had undergone numerous polypectomies and were uncontrolled on st and ard therapy with intranasal corticosteroids , leukotriene receptor antagonists and nasal douching . Aspirin treatment involved one drop ( 100 microl ) of 30 mg/ml lysine-aspirin solution to each nostril , initially daily , increased every two or three days up to a maximal of 18 drops ( 54 mg lysine-aspirin ) a day . Nasal symptoms , nitric oxide level , nasal inspiratory peak flow rate , peak expiratory flow rate and nasendoscopic grading were assessed prior to therapy and three months later . We also compared the change in endoscopic polyp scores during three months of lysine-aspirin administration with the changes which had occurred during the three months prior to administration ( during which time other therapies had been identical ) . RESULTS Nasal blockage symptoms tended to decrease ; other nasal symptoms were unchanged . Significant changes were seen in nasal inspiratory peak flow rate ( 103.3 + /- 18.9 and 140.0 + /- 16.7 l/min before and after aspirin , respectively ; p = 0.014 ) , but not in peak expiratory flow rate ( 438.7 + /- 33.4 and 440.0 + /- 28.4 l/min before and after aspirin , respectively ; p = 0.700 ) . Nasal nitric oxide levels rose significantly ( in both sides , p = 0.028 ) . Expired chest nitric oxide levels did not change . Nasal polyp scores on nasendoscopic examination were significantly reduced ( right side , p = 0.027 ; left side , p = 0.018 ) . Compared with the preceding three months , adding intranasal lysine-aspirin application had the effect on decreasing nasal polyp volume ( right side , p = 0.031 ; left side , p = 0.016 ) . CONCLUSION This open study suggests that intranasal lysine-aspirin administration reduces nasal polyp volume in aspirin-intolerant patients , without any adverse affect on concomitant asthma . This was a preliminary study and should be followed by a placebo-controlled , double-blind trial BACKGROUND Patients with aspirin-sensitive rhinosinusitis , which is frequently associated with intrinsic bronchial asthma , can be desensitized by long-term treatment with oral aspirin . The exact mechanisms of this desensitization remain obscure , but modulations of the eicosanoid pathway occur and can be monitored with the help of a practicable in vitro assay on mixed leukocyte cultures . OBJECTIVE To monitor the effect of low-dose aspirin desensitization therapy , 100 mg/d , objective ly by an in vitro assay . DESIGN In a prospect i ve study , 30 patients with aspirin intolerance , who were treated following a desensitization protocol with a dose of oral aspirin of only 100 mg/d were followed up for 1 year and reassessed every 3 months clinical ly and in vitro . RESULTS Twenty-five patients showed a normalization of in vitro eicosanoid levels during this period , 4 showed some improvement , and 1 showed no therapeutic effect on eicosanoid release . Clinical follow-up revealed a low recurrence rate of nasal polyposis , with recurrent disease only in 4 individuals who also showed no normalization of eicosanoid release levels . Furthermore , a reduction of the average incidence of purulent episodes of sinusitis was seen after 1 year . Of 12 patients with asthma , 9 experienced marked improvement in pulmonary function . Of 16 individuals with a marked impairment of nasal breathing , 14 felt an increase of nasal patency , and 7 of 11 patients with pretreatment hyposmia had an improved sense of smell after 1 year . CONCLUSIONS Desensitization therapy in patients with aspirin-sensitive rhinosinusitis can be successfully performed with low oral doses of aspirin , and the individual course throughout the desensitization can be monitored with the help of an in vitro analysis of eicosanoid release from mixed leukocyte cultures OBJECTIVES /HYPOTHESIS Evidence is lacking to guide the postoperative management of Samter 's triad patients with chronic rhinosinusitis with polyposis ( CRSwP ) undergoing endoscopic sinus surgery ( ESS ) . The purpose of this study was to compare three different st and ardized medication regimens prescribed to these patients after ESS . STUDY DESIGN Three-arm , r and omized , double-blinded , controlled trial . METHODS Patients with Samter 's triad undergoing ESS were postoperatively r and omized into three medication regimens , those being saline irrigation alone ( control group A ) , saline irrigation plus separate budesonide nasal spray ( group B ) , and saline irrigation mixed with budesonide nasal spray ( group C ) . Outcome measures were Sino-Nasal Outcome Test scores , Lund-Mackay computed tomography scores , and Lund-Kennedy endoscopic scores taken at preoperative baseline , and then at 6 months and 1 year postoperatively . Side effect profiles were also measured ( adrenocorticotropic hormone blood level ranges and intraocular pressure at the same interval points ) . Analysis of variance and χ(2 ) analyses were conducted using a Bonferroni correction method and routine descriptive statistics . Inter- and intragroup comparisons were made . RESULTS Sixty subjects were recruited . All groups were equivalent at baseline in all outcomes . All intragroup analyses showed statistically and clinical ly significant improvement in disease status as compared to baseline ( P < .0167 ) , with a sustained but lessened improvement at 1 year . However , no statistically or clinical ly significant differences were observed between groups at any time point ( P > .05 ) . There was no treatment effect noted . CONCLUSIONS In this study , nasal steroids did not confer any additional benefit over saline alone as post-ESS care for the Samter 's triad CRSwP patient population 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 Aspirin desensitization followed by daily aspirin therapy is effective add-on treatment for patients with aspirin-exacerbated respiratory disease . Prior studies used 650 mg of aspirin twice daily , but studies at lower dosages were inconclusive . OBJECTIVE We sought to determine the optimal daily dosage of aspirin treatment . METHODS We studied 137 patients who had undergone successful aspirin desensitization and r and omized them into 2 groups , 650 mg twice daily versus 325 mg twice daily . After 1 month , patients either increased or decreased their dosage based on their symptom control and continued that dosage for the remainder of the year . RESULTS Patients taking either 650 mg twice daily or 325 mg twice daily showed significant improvements in number of sinus infections , sinus operations , and hospitalizations for asthma ( all P < .0001 ) . Anosmia , nasal/sinus symptoms , and asthma symptoms also improved in both groups ( all P < .03 ) . Systemic corticosteroid dosages decreased by 3- and 4-fold in the 325 mg twice daily and 650 mg twice daily groups , respectively . Of the 137 patients , 32 had adverse effects from or discontinued aspirin therapy : 14 ( 44 % ) of 32 from the group r and omized to taking 650 mg twice daily and 18 ( 56 % ) of 32 from the group r and omized to 325 mg twice daily . The most common adverse effect was dyspepsia . CONCLUSION Both dosages were efficacious , and side effects occurred in both groups at similar frequencies . Some patients initially taking 325 mg twice daily required an increase to 650 mg twice daily for optimal symptom control . CLINICAL IMPLICATION S We recommend that patients begin daily aspirin therapy with 650 mg twice daily and subsequently decrease to the lowest effective dosage ( usually 325 mg twice daily ) BACKGROUND Aspirin (ASA)-exacerbated respiratory disease ( AERD ) is characterized by aggressive inflammation of the respiratory tract and often requires topical and /or systemic corticosteroids to maintain partial control of this disease . Previous studies have revealed that ASA desensitization and subsequent treatment with ASA is associated with clinical improvement in AERD . OBJECTIVE The aim of the present study was to determine the effect of daily ASA treatment for the first 4 weeks after ASA desensitization . METHODS Thirty-eight patients underwent ASA oral challenge followed by ASA desensitization and daily ASA therapy . Changes in nasal and asthma symptoms , combined with changes in oral prednisone , were recorded daily during 4 weeks before and after desensitization . Severity of symptoms ranged from a scale of 1 to 5 ( 1 = asymptomatic and 5 = most severe symptoms ) . For statistical analyses the sum of nasal symptoms and asthma symptoms was calculated . Olfactory scores were also analyzed . RESULTS Nasal and asthma symptom scores , as well as olfactory scores , improved significantly ( P < 0.0001 ) . For the 15 patients taking prednisone , their mean doses decreased from 10.7 to 5.9 mg daily ( P = 0.0003 ) . CONCLUSIONS Our study suggests that ASA desensitization treatment is effective during the first 4 weeks of daily treatment with ASA Nasal polyposis is a multifactorial disease with a complex and still not completely understood pathogenesis . In more than one third of cases it is associated with intolerance to acetylsalicylic acid ( aspirin , ASA ) or to other non-steroidal anti-inflammatory drugs (NSAIDs).1 In as many as 20 % of cases nasal polyposis is also associated with the presence of bronchial asthma and /or rhinitis , configuring the so-called ASA triad or aspirin disease.2 Nasal polyps may benefit from medical treatment ( corticosteroids ) and surgery,3 but they frequently relapse soon after surgery4 - 9 with significant morbidity and high social and medical costs . Unfortunately , the effect of treatment with steroids is also often temporary.3 10 - 16 In the last two decades it has been observed that , in aspirin sensitive patients , oral aspirin desensitisation ( followed by long term aspirin treatment ) often results in an improvement in the clinical course of nasal polyposis.17 - 21 We have shown that aspirin sensitive patients with nasal polyposis have a higher rate of positive nasal provocation tests ( rhinomanometric measure of nasal airflow reduction after exposure to the drug ) with lysine-acetylsalicylate ( LAS ) than aspirin sensitive patients without nasal polyps.22 - 24 Moreover , LAS has been found to have an in vitro non-specific antiproliferative , dose dependent effect on the growth of fibroblasts of both nasal polyps and normal skin.23 We have shown that long term topical ( endonasal ) treatment with LAS prevents the recurrence of nasal polyps after polypectomy with satisfactory results .24 In this paper we present and discuss the definitive results obtained in two controlled long term prospect i ve follow up studies dealing with the evaluation of relapse rates in nasal polyposis . The first is a six year follow up study of patients with nasal polyps who underwent long term intranasal LAS treatment after surgical polypectomy in comparison with matched controls ( patients who underwent UNLABELLED OBJECTIVES /PROBLEM : To determine the sinonasal effect of aspirin salicylic acid ( ASA ) desensitization in patients with nasal polyps , asthma and aspirin intolerance ( ASA triad ) . METHODS OF STUDY Patients with ASA triad were recruited from the outpatient otolaryngology clinic . They underwent a program of ASA desensitization ( 2005 - 2008 ) with prospect i ve assessment of subjective and objective responses . Incremental doses of aspirin were given to reach a target of 625 mg twice daily during a period of 3 - 5 days . A maintenance dose was then given for the study period . The patients also received inhaled and topical nasal steroids , antihistamines and beta agonists for asthma control , but no systemic steroid treatment . MAIN RESULTS Of the original 27 enrolled subjects , 10 elected to discontinue treatment and five dropped out because of treatment complications . The objective evaluation of the polypoid sinonasal disease in the remaining 12 patients ( 4 males , 8 females , age range 22 - 63 years ) revealed only mild improvement . In contrast , the patients ` subjective feeling of nasal congestion , nasal discharge and overall discomfort improved significantly . CONCLUSIONS Aspirin desensitization has a favorable subjective effect on certain nasal symptoms among ASA triad patients , but the objective effect on polypoid mass is not significant BACKGROUND Patients with aspirin-exacerbated respiratory disease have been shown to benefit clinical ly from aspirin desensitization followed by chronic high-dose aspirin therapy . However , the mechanism of this phenomenon is still unclear . OBJECTIVE The aim of this study was to characterize the airway inflammatory response to aspirin desensitization and after treatment with high-dose aspirin for 6 months . METHODS Twenty-one adult patients with asthma , chronic polypoid sinusitis , and a convincing history of acute respiratory reaction to the ingestion of aspirin or nonsteroidal anti-inflammatory drugs were selected . These patients underwent an oral desensitization to aspirin over a 2-day period , followed by daily ingestion of aspirin 650 mg twice daily . Induced sputum sample s and exhaled nitric oxide measurements were taken before the procedure , during the second day of the procedure , and after 6 months of treatment . RESULTS There was a significant elevation in both the exhaled nitric oxide level ( P = .03 ) and sputum tryptase level ( P = .05 ) during the desensitization process . After 6 months of aspirin treatment , sputum IL-4 ( P = .0007 ) and matrix metalloproteinase 9 ( MMP-9 ; P = .05 ) decreased significantly compared with baseline . Predesensitization to postdesensitization changes in MMP-9 and tissue inhibitors of metalloproteinases 1 were highly correlated ( r = 0.79 ; P = .0003 ) . Immediately after the desensitization , MMP-9 and tryptase were correlated ( r = 0.82 ; P = .001 ) , whereas IL-4 was inversely related with FMS-like tyrosine kinase 3 lig and ( FLT3-L ) ( r = -0.79 ; P = .0008 ) . There was a significant decrease in the average symptom score at 6 months . CONCLUSION Consistent with previous reports , acute aspirin desensitization in patients with aspirin-exacerbated respiratory disease involves mast cell degranulation . In contrast , long-term treatment with aspirin involves suppression of IL-4 as well as downregulation of proinflammatory MMP-9 while T(H)1 marker FLT3-L increases OBJECTIVES /HYPOTHESIS Intranasal lysine-aspirin has been used as a method of desensitization in patients with aspirin-sensitive nasal polyps to control their recurrence and prevent frequent surgical intervention . However , the studies are limited in number , and their design is open to criticisms . Thus , we conducted a controlled trial to study the clinical effectiveness of topical lysine-aspirin in patients with aspirin-sensitive nasal polyposis . STUDY DESIGN Prospect i ve , r and omized , double blind , placebo controlled , crossover trial . METHODS Aspirin-sensitive patients confirmed by intranasal challenge were enrolled and r and omized to receive 16 mg of topical lysine-aspirin every 48 hours or placebo for 6 months before crossover . Polyp growth and nasal and chest symptoms were monitored using acoustic rhinometry , nasal inspiratory peak flow , peak expiratory flow rate , and a daily diary of symptom scores . RESULTS Twenty-two patients were enrolled . After withdrawals and drop outs , data were available on 11 patients for analysis . Multivariate analysis of measured parameters did not reveal a significant clinical benefit to patients receiving topical lysine-aspirin compared with placebo . Deterioration was similar while on lysine-aspirin or placebo . CONCLUSIONS This is the first controlled clinical trial of topical desensitization in aspirin-sensitive nasal polyp patients . Despite the failure to demonstrate clinical benefit , tissue studies have shown a significant improvement at the microscopic level . Further work with larger numbers of patients along with conventional treatment may show a clinical improvement in these patients |
1,223 | 28,485,020 | No difference found on the quantity of CD34 + cells collected , number of apheresis procedure in successful mobilization , level of peak PB CD34 + cells achieved , and day of neutrophil and platelet engraftment | Granulocyte-colony stimulating factor ( G-CSF ) mobilizes and increases the amount of hematopoietic stem cells in peripheral blood , enabling its harvest by few apheresis procedures .
The pegylated G-CSF has longer half-life and is given once only , which is more comfortable for patients , whereas the non-pegylated requires multiple daily injection because of its short half-life .
We summarized results of r and omized trials comparing the efficacy and safety of pegylated and non-pegylated G-CSF for peripheral blood stem cell mobilization . | A r and omised trial in breast cancer patients was design ed to compare the number of peripheral blood progenitor cells collected after mobilisation with a single dose of 10 microg/kg/day granulocyte colony-stimulating factor ( G-CSF ) ( n=14 ) or a split dose of 5 microg/kg twice daily ( n=14 ) . Both groups were well balanced . No significant differences were observed between groups regarding aphereses parameters . The total number of CD34 + cells collected was higher in the split-dose group ( mean of 7.1 and median of 7.4 x 10(6)/kg ) than in the single-dose group ( 5.6 and 5.8 x 10(6)/kg , respectively ) ( P=0.26 ) . The mean of CD34 + cells collected after the first apheresis procedure was 3.9 x 10(6)/kg for the split dose group and 3.1 x 10(6)/kg for the single-dose group ( P=0.24 ) . Circulating CD34 + cells before the first apheresis were higher for the split-dose group ( mean 79.7 vs 59.2 x 10(6)/l ) ( P=0.14 ) . All bone pain scores applied were significantly higher for the split-dose group . Our primary end point of improving the mean of total CD34 + cells collected to 2.5 x 10(6)/kg was not achieved with twice-daily G-CSF administration . Further studies evaluating different mobilisation schedules with G-CSF are needed to determine the optimal regimen AIM To evaluate in a multicentre r and omised study the effect on duration of febrile neutropenia ( FN ) , the safety and cost-effectiveness of a single subcutaneous pegfilgrastim injection compared with daily injections of filgrastim after peripheral blood stem cell transplantation in patients receiving high dose chemotherapy for myeloma and lymphoma . METHODS Patients were r and omly assigned to a single dose of pegfilgrastim at day 5 ( D5 ) or daily filgrastim from D5 to the recovery of absolute neutrophil count ( ANC ) to 0.5 G/L. Duration of FN , of neutrophil and platelet recovery , transfusion and antibiotic requirements were the main end-points of the study . Costs were calculated from D0 until transplant unit discharge . The incremental cost-effectiveness ratio was expressed as the cost per day of FN prevented . Probabilistic sensitivity analysis was performed by non-parametric bootstrap methods . RESULTS Between October 2008 and September 2009 , 10 centres enrolled 151 patients : 80 patients with lymphoma and 71 patients with myeloma . The mean duration of FN was 3.07 days ( st and ard deviation ( SD ) 1.96 ) in the pegfilgrastin arm and 3.29 ( SD 2.54 ) in the filgrastim one . Mean total costs were 23,256 and 25,448 euros for pegfilgrastim and filgrastim patients , respectively . There was a 62 % probability that pegfilgrastim strictly dominates filgrastim . CONCLUDING STATEMENT Pegfilgrastim after PBSC transplantation in myeloma and lymphoma is safe , effective when compared with filgrastim and could represent a cost-effective alternative in this setting Purpose : To compare the effectiveness , tolerance , and pharmacokinetics of a single dose of pegfilgrastim to daily filgrastim in children and young adults with sarcomas treated with dose-intensive combination chemotherapy . Experimental Design : Patients were r and omized to receive a single dose of 100 mcg/kg of pegfilgrastim s.c . or 5 mcg/kg/day of filgrastim s.c . , daily until neutrophil recovery after two treatment cycles with vincristine , doxorubicin , and cyclophosphamide ( VDC ) and two cycles of etoposide and ifosfamide ( IE ) . The duration of severe neutropenia ( absolute neutrophil count , ≤500/mcL ) during cycles 1 to 4 and cycle duration for all cycles were compared . Pharmacokinetics of pegfilgrastim and filgrastim and CD34 + stem cell mobilization were studied on cycle 1 . Growth factor – related toxicity , transfusions , and episodes of fever and neutropenia and infections were collected for cycles 1 to 4 . Results : Thirty-four patients ( median age , 20 years ; range 3.8 - 25.8 ) were enrolled , and 32 completed cycles 1 to 4 . The median ( range ) duration of absolute neutrophil count of < 500/mcL was 5.5 ( 3 - 8 ) days for pegfilgrastim and 6 ( 0 - 9 ) days for filgrastim ( P = 0.76 ) after VDC , and 1.5 ( 0 - 4 ) days for pegfilgrastim and 3.75 ( 0 - 6.5 ) days for filgrastim ( P = 0.11 ) after IE . More episodes of febrile neutropenia and documented infections occurred on the filgrastim arm . Serum pegfilgrastim concentrations were highly variable . Pegfilgrastim apparent clearance ( 11 mL/h/kg ) was similar to that reported in adults . Conclusion : A single dose per cycle of pegfilgrastim was well tolerated and may be as effective as daily filgrastim based on the duration of severe neutropenia and number of episodes of febrile neutropenia and documented infections after dose-intensive treatment with VDC and IE . ( Clin Cancer Res 2009;15(23):7361–7 Patients with lymphoproliferative disorders , c and i date to autologous stem cell transplantation ( ASCT ) , require mobilization with chemotherapy and granulocyte colony -stimulating factor ( G-CSF ) . This study looked for differences in hematopoietic peripheral stem cells ( HPSCs ) mobilization in response to the three available G-CSFs , namely lenograstim , filgrastim , and pegfilgrastim . Between 2000 and 2012 , 146 patients ( 66 M and 80 F ) who underwent ASCT for multiple myeloma , non-Hodgkin ’s lymphoma or Hodgkin ’s lymphoma were studied . All patients received induction therapy and then a mobilization regimen with cyclophosphamide plus lenograstim , or filgrastim , or pegfilgrastim . From days 12 to 14 , HPSCs were collected by two to three daily leukaphereses . Our results show that high-dose cyclophosphamide plus lenograstim achieved adequate mobilization and the collection target more quickly and with fewer leukaphereses as compared to filgrastim and pegfilgrastim . No differences between the three regimens were observed regarding toxicity and days to WBC and platelet recovery . Thus , lenograstim may represent the ideal G-CSF for PBSC mobilization in patients with lymphoproliferative diseases . Further studies are needed to confirm these results and better underst and the biological bases of these differences Ro 25‐8315 is produced by conjugation of rhG‐CSF mutant with polyethylene glycol ( PEG ) . The purpose of this study was to examine the pharmacodynamics and pharmacokinetics of Ro 25‐8315 in comparison with Filgrastim ( rhG‐CSF ) . Subjects received single subcutaneous doses of Ro 25‐8315 ranging from 10 to 150 μg/kg using a double‐blind , r and omized , placebo‐controlled design . Filgrastim was administered as a single dose ( 5 or 10 μg/kg ) and , following a 14‐day washout period , daily for 7 days . Ro 25‐8315 increased absolute neutrophil count ( ANC ) by 6‐ to 8‐fold and CD34 + cell count more than 30‐fold at the highest doses tested . Single doses ( 60–150 μg/kg ) of Ro 25‐8315 and multiple doses of Filgrastim had similar effects on ANC and CD34 + , although Ro 25‐8315 had a greater effect on CFU‐GM . The pharmacokinetics of Ro 25‐8315 were dose‐dependent , with peak concentrations and area under the serum concentration – time curve ( AUC ) increasing 100‐fold over the range of doses studied . Time to reach peak concentration ( Tmax ) and half‐life of Ro 25‐8315 averaged 20–30 hr at all doses , approximately three times longer than with Filgrastim . Adverse events were not serious and occurred with similar frequency with both products . Pegylation of rhG‐CSF mutant results in more desirable pharmacokinetic properties and a longer duration of action with effective increases in ANC and measures of peripheral blood progenitor cell mobilization for at least 1 week . Am . J. Hematol . 66:245–251 , 2001 . © 2001 Wiley‐Liss , Goals of workRecently , 6 cycles of R-CHOP-14 have been recommended as the reference st and ard regimen for the treatment of elderly patients with diffuse large B-cell lymphoma ( DLBCL ) . Pegfilgrastim has been shown to facilitate dose-dense chemotherapy schedules with a single administration per chemotherapy cycle . The aims of this study were to evaluate the use of pegfilgrastim in combination with the R-CHOP-14 regimen in a homogenous group of previously untreated elderly patients with DLBCL and to assess the pharmacokinetics of pegfilgrastim within this patient population . Material s and methods Ten patients with DLBCL between 60 and 80 years of age received a single subcutaneous injection of 6 mg pegfilgrastim 24 h after administration of R-CHOP chemoimmunotherapy , which was repeated for 6 to 8 cycles in two-weekly intervals . A total of 348 blood sample s were collected . Pegfilgrastim plasma levels and absolute neutrophil counts were measured every other day during the first treatment cycle and twice weekly during all consecutive cycles . Main results Sixty-three of 72 cycles ( 87.5 % ) could be delivered on time and at the planned dose . Median absolute neutrophil nadir was 0.32 g/l on day 9 . Grade 3/4 granulocytopenia occurred in all patients . Febrile neutropenia occurred in two patients . Plasma levels of pegfilgrastim remained elevated during the neutropenic phase . At the start of hematologic recovery , plasma concentrations of pegfilgrastim decreased rapidly to baseline levels . Median pegfilgrastim trough plasma level was 0.43 ng/ml on the day preceding the next application . Conclusions A single fixed dose of 6 mg of pegfilgrastim given once per cycle of R-CHOP-14 is effective in supporting neutrophil recovery to allow two-weekly drug administration in previously untreated elderly patients with DLBCL . However , close monitoring for infectious complications is m and atory in this patient population BACKGROUND It is not known whether increasing the dose of filgrastim after mobilizing chemotherapy improves collection of peripheral blood progenitor cells ( PBPC ) and leads to faster hematopoietic engraftment after autologous transplantation . STUDY DESIGN AND METHODS A r and omized , open-label , multicenter trial was carried out in patients with breast cancer , multiple myeloma , and lymphoma , in which patients were r and omized to receive 5 or 10 microg per kg per day of filgrastim after st and ard chemotherapy to mobilize PBPCs . After high-dose chemotherapy , the components from the first two leukapheresis procedures were returned , and all patients received 5 microg per kg day of filgrastim after transplantation . RESULTS A total of 131 patients were r and omized , of whom 128 were mobilized ( Group A , 5 microg/kg , n = 66 ; Group B , 10 microg/kg , n = 62 ) and 112 were transplanted . Only six patients were not transplanted because of insufficient CD34 + cell numbers . The median number of CD34 + cells collected in the first two leukapheresis procedures tended to be higher in Group B than in Group A ( 12.0 vs. 7.2 x 10(6)/kg , NS ) , but after transplantation there was no significant difference in median times to platelet ( 9 days in both groups ) or neutrophil ( 8 days in both groups ) engraftment or the number of platelet transfusions ( three in both groups ) . A subsequent subgroup analysis separating patients transplanted after first- or second-line chemotherapy also showed no measurable impact of filgrastim dose on the median CD34 + cell yield or on platelet engraftment in either subgroup . CONCLUSION PBPC mobilization with chemotherapy and 5 microg per kg of filgrastim is very efficient , and 10 microg per kg of filgrastim does not provide additional clinical benefit Summary . To date , no r and omized study has compared different doses of recombinant human granulocyte colony‐stimulating factor ( rhG‐CSF ) following submyeloablative mobilization chemotherapy . Therefore , we evaluated the effect of different doses of rhG‐CSF following mobilization chemotherapy on yields of CD34 + peripheral blood stem cells ( PBSC ) . Fifty patients were r and omized to receive 8 ( n = 25 ) versus 16 µg/kg/d ( n = 25 ) of rhG‐CSF following mobilization chemotherapy . The median number of CD34 + cells collected after 8 µg/kg/d of rhG‐CSF was 2·36 × 106/kg ( range , 0·21–7·80 ) , compared with 7·99 ( 2·76–14·89 ) after 16 µg/kg/d ( P < 0·001 ) . Twenty out of 25 ( 80 % ) patients in the low‐dose and 23 out of 25 ( 92 % ) in the high‐dose rhG‐CSF arm underwent high‐dose chemotherapy ( HDC ) and autologous stem cell transplantation ( ASCT ) . Median days to white blood cell engraftment in patients mobilized with 8 µg/kg and 16 µg/kg of rhG‐CSF were 12 ( 10–20 ) and 9 ( 8–11 ) respectively ( P < 0·001 ) . There was no difference between the two groups regarding the other parameters of peritransplant morbidity : days to platelet engraftment ( P = 0·10 ) , number of red blood cell ( P = 0·56 ) and platelet transfusions ( P = 0·22 ) , days of total parenteral nutrition requirement ( P = 0·84 ) , fever ( P = 0·93 ) and antibiotics ( P = 0·77 ) , and number of different antibiotics used ( P = 0·58 ) . These data showed that higher doses of rhG‐CSF following submyeloablative mobilization chemotherapy were associated with a clear dose – response effect based on the collected cell yields . Based on the parameters of peritransplant morbidity , 8 µg/kg/d was as effective as 16 µg/kg/d except for a rapid neutrophil engraftment in the high‐dose arm . Therefore , in routine clinical practice , despite some advantage in the use of higher doses of rhG‐CSF , lower doses may be used for PBSC collection s following chemotherapy‐based mobilization regimens in this cost‐conscious era The efficacy of pegfilgrastim±chemotherapy for mobilizing stem cells in patients with solid tumours was assessed . In cycle 0 , a 14-day prechemotherapy cycle , patients ( N=61 ) were r and omized open-label to single doses of pegfilgrastim ( 6 , 12 or 18 mg ) on day 1 , or daily filgrastim ( 10 μg/kg ) for ⩽7 days . Mean peak peripheral CD34 + cell counts increased with pegfilgrastim dose , but were significantly higher than filgrastim only at the 18 mg dose ( 10.17 vs 4.96 × 104/ml ; P=0.014 ) . In the clinical ly relevant period of days 3–7 , both 12 and 18 mg pegfilgrastim doses produced significantly higher peak CD34 + counts ( 8.18 and 9.96 vs 4.51 × 104/ml for filgrastim ; P=0.034 and 0.006 ) . In cycle 1 , patients received carboplatin/paclitaxel on day 1 , followed from day 2 by pegfilgrastim 6–18 mg or daily filgrastim ( 5 μg/kg/day for ⩽14 days ) as per r and omization in cycle 0 . There were no significant differences in mean peak CD34 + count between pegfilgrastim and filgrastim , but there was an advantage for pegfilgrastim 18 mg in the relevant period of days 7–12 ( 3.14 vs 1.19 × 104/ml ; P=0.043 ) . A single pegfilgrastim dose ( ⩾6 mg ) could be substituted for daily filgrastim in cytokine-only peripheral CD34 + cell mobilization High-dose chemotherapy followed by autologous blood stem cell transplantation is the st and ard treatment for myeloma patients . In this study , CAD ( cyclophosphamide , adriamycin , dexamethasone ) chemotherapy and a single dose of pegfilgrastim ( 12 mg ) was highly effective in mobilizing peripheral blood stem cells ( PBSCs ) for subsequent transplantation , with 88 % of patients ( n=26 ) achieving the CD34 + cell harvest target of ⩾7.50 × 106 CD34 + cells/kg body weight , following a median of two apheresis procedures ( range 1–4 ) and with first apheresis performed at a median day 13 after CAD application ( range 10–20 ) . Patients treated with pegfilgrastim showed a reduced time to first apheresis procedure from mobilization compared with filgrastim-mobilized historical matched controls ( n=52 , P=0.015 ) . The pegfilgrastim mobilization regimen allowed for transplantation of a median of 3.58 × 106 CD34 + cells/kg body weight while leaving sufficient stored cells for a second high-dose regimen and back-ups in most patients . Engraftment following transplantation was comparable to filgrastim , with a median time of 14 days to leucocyte ⩾1.0 × 109/l ( range 10–21 ) and 11 days to platelets ⩾20 × 109/l ( range 0–15 ) . The results of this study thus provide further support for the clinical utility of pegfilgrastim for the mobilization of PBSC following chemotherapy in cancer patients scheduled for transplantation OBJECTIVES Prophylaxis with granulocyte-colony stimulating factor ( G-CSF ) reduces the risk of febrile neutropenia ( FN ) in patients receiving myelosuppressive chemotherapy . R and omized clinical trials have shown that pegfilgrastim , a 2nd-generation G-CSF , is at least as effective as the 1st-generation G-CSF filgrastim . In the meta- analysis of trials pegfilgrastim performed better than filgrastim with respect to FN risk . The incremental cost-effectiveness of primary prophylaxis ( starting in cycle 1 and continuing in subsequent cycles of chemotherapy ) with pegfilgrastim versus filgrastim used for 6 days ( as is often used in clinical practice ) was estimated in patients with aggressive non-Hodgkin 's lymphoma ( NHL ) receiving myelosuppressive chemotherapy in the United States . METHODS A decision-analytic model was constructed from a health insurer 's perspective with a life-time study horizon . The model considered direct medical costs and outcomes related to reduced FN and potential survival benefits due to reduced FN-related mortality . Inputs for the model were obtained from the medical literature . Sensitivity analyses were conducted across plausible ranges in parameter values . RESULTS The incremental cost-effectiveness ( ICER ) of pegfilgrastim versus 6-day filgrastim primary prophylaxis was $ 2167/FN episode avoided . Adding survival benefit from avoiding FN mortality yielded an ICER of $ 5532/LY gained or $ 6190/QALY gained . When the potential benefit of optimized chemotherapy was included , the ICER was $ 1494/LY gained or $ 1677/QALY gained . The most influential factors included cost of pegfilgrastim , relative risk of FN between pegfilgrastim and filgrastim , FN case-fatality rate , cost of filgrastim and baseline FN risk . CONCLUSIONS Pegfilgrastim is cost-effective in primary prophylaxis of FN compared to 6 days per cycle of filgrastim , in patients with NHL receiving myelosuppressive chemotherapy ( e.g. , cyclophosphamide + doxorubicin + vincristine + prednisolone [ CHOP-21 ] ) chemotherapy . Study limitations included lack of direct evidence linking G-CSF use with a reduction in FN-related mortality and limited data that show a relationship between relative dose intensity ( RDI ) and cancer-specific patient survival This phase 2 r and omized , double-blind trial examines the efficacy of pegfilgrastim and filgrastim for mobilizing peripheral blood progenitors cells following chemotherapy in patients with non-Hodgkin ’s lymphoma . The results of the study suggest that pegfilgrastim may provide a suitable alternative to filgrastim in this setting . Background Growth factors are frequently used to aid peripheral blood progenitor cell mobilization from bone marrow . This phase 2 study examined the efficacy and safety of pegfilgrastim for mobilizing peripheral blood progenitors cells for autologous transplantation . Design and Methods Patients with non-Hodgkin ’s lymphoma received one cycle of mobilizing chemotherapy ( ifosfamide , carboplatin and etoposide , ICE ) . Twenty-four hours later they were r and omized , double-blind , to receive a single dose of pegfilgrastim 6 mg or 12 mg , or filgrastim 5 μg/kg/day ( until the end of leukapheresis ) . Following leukapheresis ( collection phase ) , patients rested or received one or two ‘ salvage ’ cycles of ICE . High-dose BEAM chemotherapy was then given before peripheral blood progenitor cell transplantation . The primary end-point was the patients ’ mean yield of CD34 + cells/kg during the collection phase . Results Ninety patients were r and omized and received a study drug ; 63 % completed the collection phase . The patients ’ mean ( 95 % CI ) CD34 + cell harvest per leukapheresis was 0.8 ( 0.5–1.4 ) , 0.8 ( 0.5–1.6 ) and 1.2 (0.7–2.0) × 106 cells/kg for the pegfilgrastim 6 mg , pegfilgrastim 12 mg and filgrastim groups , respectively . Twenty ( 69 % ) , 17 ( 59 % ) and 23 ( 72 % ) patients in these three groups achieved the targeted minimum harvest ( ≥2 × 106 cells/kg ) . The mean total harvests were 1.7 , 1.4 and 2.2 × 106 cells/kg , respectively . Post-transplantation , the median days to absolute neutrophil count recovery ( ≥0.5 × 109/L ) were 12 , 11 , and 11 , respectively . Pegfilgrastim and filgrastim were generally well tolerated . Conclusions Pegfilgrastim ( 6 or 12 mg ) was effective for mobilizing peripheral blood progenitors cells in patients with non-Hodgkin ’s lymphoma . These data may aid the design of studies to clarify optimal dosing and leukapheresis with pegfilgrastim Pegfilgrastim has equivalent efficacy to daily G-CSF in enhancing neutrophil recovery after chemotherapy , but conclusive data concerning its use for peripheral blood stem cell ( PBSC ) mobilization are lacking . From 2003 to 2008 we used high-dose chemotherapy in 64 lymphoma patients . At mobilization chemotherapy ( ESHAP ) the first 26 patients used unconjugated G-CSF , while the remaining 38 patients received Pegfilgrastim . At the time of harvest 25 patients collected stem cells after the use of G-CSF and 36 in the Peg group . No statistical by significant differences were observed in median peripheral CD34 + cells mobilized ( 77 μL versus 71 μL ) and in collected PBSC ( 12.3 × 10(6)/kg versus 9.4 × 10(6)/kg p = 0.76 ) . In the PEG group all patients collected the target PBSC with a single apheresis with a greater proportion of " optimal " mobilizers ( 83 % versus 64 % ; p = 0.05 ) . In conclusion a single dose of Pegfilgrastim could be a valid alternative to unconjugated G-CSF to mobilize PBSC in lymphoma patients BACKGROUND Current regimens for peripheral blood progenitor cell ( PBPC ) mobilization in patients with multiple myeloma are based on daily subcutaneous injections of granulocyte-colony-stimulating factor ( G-CSF ) starting shortly after cytotoxic therapy . Recently a polyethylene glycol-conjugated G-CSF ( pegfilgrastim ) was introduced that has a substantially longer t(1/2 ) than the original formula . STUDY DESIGN AND METHODS The use of pegfilgrastim was examined at two dose levels for PBPC mobilization in patients with Stage II or III multiple myeloma . Four days after cytotoxic therapy with cyclophosphamide ( 4 g/m(2 ) ) , a single dose of either 6 mg pegfilgrastim ( n = 15 ) or 12 mg pegfilgrastim ( n = 15 ) or daily doses of 8 microg per kg unconjugated G-CSF ( n = 15 ) were administered . The number of circulating CD34 + cells was determined during white blood cell ( WBC ) recovery , and PBPC harvesting was performed by large-volume apheresis . RESULTS Pegfilgrastim was equally potent at 6 and 12 mg with regard to mobilization and yield of CD34 + cells . No dose dependence was observed because CD34 + cell concentration peaks were 131 and 85 per microL , respectively , and CD34 + cell yield was 10.2 x 10(6 ) and 7.4 x 10(6 ) per kg of body weight , respectively . Pegfilgrastim in either dose was associated with a more rapid WBC recovery ( p = 0.03 ) and an earlier performance of the first apheresis procedure ( p < 0.05 ) in comparison to unconjugated G-CSF . No difference regarding CD34 + cell maximum and yield could be observed . CONCLUSION A single dose of 6 mg pegfilgrastim is equally potent as 12 mg for mobilization and harvest of PBPCs in patients with multiple myeloma . Because no dose dependency was seen at these dose levels , this might be also true for even smaller doses Summary : Following induction therapy and 4 g/m2 cyclophosphamide , a single dose of 12 mg polyethyleneglycol-conjugated G-CSF ( pegfilgrastim ; n=12 ) or daily doses of unconjugated G-CSF ( 8.5 μg/kg/day ) ( n=12 ) were administered to myeloma patients . Pegfilgrastim was associated with an earlier leukocyte recovery ( 12 vs 14 days ) and peripheral blood CD34 + cell peak ( 12 vs 15 days ) . The peripheral blood CD34 + cell peak was lower in the pegfilgrastim group ( 78 vs 111/μl ) . Following high-dose melphalan ( 200 mg/m2 ) and autografting , leukocyte and platelet reconstitution was similar in both groups and stable blood counts were observed 100 days post transplant . In summary , a single dose of pegfilgrastim after chemotherapy is capable of mobilizing a sufficient number of CD34 + cells for successful autografting with early engraftment and sustained hematological reconstitution in patients with myeloma . These data provide the basis for r and omized studies evaluating the optimal dose and time of pegfilgrastim as well as long-term outcome in larger cohorts of patients In patients with hematologic malignancies , granulocyte colony-stimulating factor ( G-CSF ) following chemotherapy is widely used to mobilize peripheral blood progenitor cells ( PBPCs ) , but there have been no trials comparing schedules of G-CSF following chemotherapy . We conducted a prospect i ve r and omized comparative observation of the mobilization with a single dose ( 10 μg kg once a day ) or split dose ( 5 μg kg twice a day ) of lenograstim following chemotherapy in 25 multiple myeloma ( MM ) and 15 non-Hodgkin ’s lymphoma ( NHL ) patients . Chemotherapy was cyclophosphamide 4 g/m2 for MM and ESHAP with or without Rituximab for NHL . The median number of harvested CD34 + cells was 19.4 × 106/kg and 15.8 × 106/kg in the single- and split-dose groups , respectively ( p=0.47 ) . Targeted collection of 5 × 106 CD34 + cells/kg was achieved in 18/20 patients in the single-dose group and in all 20 patients of the split-dose group ( p=0.24 ) , with the median number of sessions 1 and 2 in the single- and split-dose groups , respectively ( p=0.13 ) . We could not observe statistically significant differences between a single-dose and split-dose lenograstim following chemotherapy in enhancing the mobilization of PBPCs in MM or NHL patients PURPOSE To explore the use of SD/01 ( a polyethylene glycol-conjugated filgrastim shown in pre clinical studies to have a prolonged half-life ) in patients with chemotherapy-induced neutropenia . PATIENTS AND METHODS Thirteen patients with non-small-cell lung cancer were r and omized to receive daily filgrastim ( 5 microg/kg/d ) or a single injection of SD/01 ( 30 , 100 , or 300 microg/kg ) 2 weeks before chemotherapy and again 24 hours after administration of carboplatin and paclitaxel . Pharmacodynamic , pharmacokinetic , and safety analyses were performed . RESULTS Peak serum concentrations of SD/01 and the duration of increased serum concentrations were dependent on the SD/01 dose . SD/01 concentrations remained increased longer in patients with chemotherapy-induced neutropenia . Prechemotherapy median absolute neutrophil counts ( ANCs ) in patients receiving SD/01 were increased in a dose-dependent fashion , with the duration of this effect also being dose dependent . After chemotherapy , median ANC nadirs were similar in the filgrastim cohort and the cohort receiving SD/01 30 microg/kg , with higher nadirs seen in the cohorts receiving SD/01 100 or 300 microg/kg . Dose-limiting toxicities were not noted . CD34(+ ) cells were mobilized in all cohorts . CONCLUSION A single dose of SD/01 increases the serum concentration of SD/01 for several days in a dose-dependent fashion and is not associated with significant toxicity . The effects of SD/01 on ANC and CD34(+ ) cell mobilization are comparable or greater than those achieved with daily filgrastim . The self-regulation of this molecule provides a potential therapeutic advantage in a variety of clinical setting s associated with neutropenia To evaluate the schedule dependency of granulocyte colony‐stimulating factor ( G‐CSF ) ( filgrastim ) for stem cell mobilization , we conducted a r and omized comparison in 50 healthy donors , with one subcutaneous daily injection of 10 µg/kg G‐CSF ( n = 25 ) compared with twice injections daily of 5 µg/kg G‐CSF ( n = 25 ) . The two groups were well balanced for age , body weight and sex . G‐CSF application was performed on an out‐patient basis and leukapheresis was started in all donors on day 5 . The most frequent side‐effects of G‐CSF were mild to moderate bone pain ( 88 % ) , mild headache ( 72 % ) , mild fatigue ( 48–60 % ) and nausea ( 8 % ) without differences between the two groups . The CD34 + cell count in the first apheresis was 5·4 × 106/kg donor weight ( range 2·8–13·3 ) in the 2 × 5 µg/kg group compared with 4·0 × 106/kg ( range 0·4–8·8 ) in the 1 × 10µg/kg group ( P = 0·007 ) . The target of collecting > 3·0 × 106 CD34 + cells/kg donor weight with one apheresis procedure was achieved in 24/25 ( 96 % ) donors in the 2 × 5 µg/kg group and in 17/25 ( 68 % ) donors in the 1 × 10 µg/kg group . The target of collecting > 5·0 × 106 CD34 + cells/kg in the first apheresis was achieved in 64 % in the 2 × 5µg/kg group , but in only 36 % in the 1 × 10 µg/kg group . The progenitor cell assay for granulocyte – macrophage colony‐forming units ( CFU‐GM ) and erythroid burst‐forming units ( BFU‐E ) was higher in the 2 × 5 µg/kg group than in the 1 × 10 µg/kg group ( 7·0 vs. 3·5 × 105/kg , P = 0·01 ; 6·6 vs. 5·0 × 105/kg ; P = 0·1 ) . Administering G‐CSF ( filgrastim ) at a dosage of 5 µg/kg twice daily rather than 10 µg/kg once daily is recommended ; this leads to a higher CD34 + cell yield and requires fewer apheresis procedures without increasing toxicity or cost There are few r and omized trials comparing filgrastim and pegfilgrastim in peripheral blood stem cell mobilization ( PBSCM ) . None of the trials studied the effects of the timing of pegfilgrastim administration on the outcomes of mobilization . We conducted a r and omized triple blind control trial comparing the outcomes of filgrastim 5 µg/kg daily from day 3 onwards , ' early ' pegfilgrastim 6 mg on day 3 and ' delayed ' pegfilgrastim 6 mg on day 7 in cyclophosphamide PBSCM in patients with no previous history of mobilization . Peripheral blood ( PB ) CD34 + cell count was checked on day 8 and day 11 onward . Apheresis was started when PB CD34 + ≥ 10/µl from day 11 onward . The primary outcome was the successful mobilization rate , defined as cumulative collection of ≥ 2 × 10(6)/kg CD34 + cells in three or less apheresis . The secondary outcomes were the day of neutrophil and platelet engraftment post transplantation . There were 156 patients r and omized and 134 patients ' data analyzed . Pegfilgrastim 6 mg day 7 produced highest percentage of successful mobilization , 34 out of 48 ( 70.8 % ) analyzed patients , followed by daily filgrastim , 28 out of 44 ( 63.6 % ) and day 3 pegfilgrastim , 20 out of 42 ( 47.6 % ) ( p = 0.075 ) . Pegfilgrastim day 7 and daily filgrastim reported 1.48 ( p = 0.014 ) and 1.49 ( p = 0.013 ) times higher successful mobilization rate respectively as compared to pegfilgrastim day 3 after adjusting for disease , gender and exposure to myelotoxic agent . Multiple myeloma patients were three times more likely to achieve successful mobilization as compared to acute leukemia or lymphoma patients . Pegfilgrastim avoided the overshoot of white cells compared to filgrastim . There was no difference in the duration of both white cells and platelet recovery post transplantation between the three interventional arms |
1,224 | 24,841,952 | Overall , CDSSs for professionals were ineffective .
Usage of the systems was generally low : in the only trial at low risk of bias the CDSS was not used at all .
When a CDSS was used , compliance with the advice offered was also low .
However , if actually used , CDSSs could result in closer guideline adherence ( improve investigating , prescribing and issuing of action plans ) and could improve some clinical outcomes .
The study at moderate risk of bias showed increased prescribing of inhaled steroids .
Conclusions : The current generation of CDSSs is unlikely to result in improvements in outcomes for patients with asthma because they are rarely used and the advice is not followed . | Background : Increasing use of electronic health records offers the potential to incorporate computer decision support systems ( CDSSs ) to prompt evidence -based actions within routine consultations .
Aim : To synthesis e the evidence for the use of CDSSs by professionals managing people with asthma . | Abstract Objective : To evaluate the use of a computerised support system for decision making for implementing evidence based clinical guidelines for the management of asthma and angina in adults in primary care . Design : A before and after pragmatic cluster r and omised controlled trial utilising a two by two incomplete block design . Setting : 60 general practice s in north east Engl and . Participants : General practitioners and practice nurses in the study practice s and their patients aged 18 or over with angina or asthma . Main outcome measures : Adherence to the guidelines , based on review of case notes and patient reported generic and condition specific outcome measures . Results : The computerised decision support system had no significant effect on consultation rates , process of care measures ( including prescribing ) , or any patient reported outcomes for either condition . Levels of use of the software were low . Conclusions : No effect was found of computerised evidence based guidelines on the management of asthma or angina in adults in primary care . This was probably due to low levels of use of the software , despite the system being optimised as far as was technically possible . Even if the technical problems of producing a system that fully supports the management of chronic disease were solved , there remains the challenge of integrating the systems into clinical encounters where busy practitioners manage patients with complex , multiple conditions OBJECTIVE : Asthma continues to be 1 of the most common chronic diseases of childhood and affects ∼6 million US children . Although National Asthma Education Prevention Program guidelines exist and are widely accepted , previous studies have demonstrated poor clinician adherence across a variety of population s. We sought to determine if clinical decision support ( CDS ) embedded in an electronic health record ( EHR ) would improve clinician adherence to national asthma guidelines in the primary care setting . METHODS : We conducted a prospect i ve cluster-r and omized trial in 12 primary care sites over a 1-year period . Practice s were stratified for analysis according to whether the site was urban or suburban . Children aged 0 to 18 years with persistent asthma were identified by International Classification of Diseases , Ninth Revision codes for asthma . The 6 intervention- practice sites had CDS alerts imbedded in the EHR . Outcomes of interest were the proportion of children with at least 1 prescription for controller medication , an up-to- date asthma care plan , and the performance of office-based spirometry . RESULTS : Increases in the number of prescriptions for controller medications , over time , was 6 % greater ( P = .006 ) and 3 % greater for spirometry ( P = .04 ) in the intervention urban practice s. Filing an up-to- date asthma care plan improved 14 % ( P = .03 ) and spirometry improved 6 % ( P = .003 ) in the suburban practice s with the intervention . CONCLUSION : In our study , using a cluster-r and omized trial design , CDS in the EHR , at the point of care , improved clinician compliance with National Asthma Education Prevention Program guidelines AIM To compare the degree of asthma control in 2001 and 2005 in a primary care setting in Sweden . METHOD Two similar question naire surveys were performed in 2001 and 2005 with 1,012 and 224 asthma patients aged 18 - 45 r and omly selected from 42 and 56 primary health care centres , respectively . A classification of asthma control similar to the GINA guidelines was made using information obtained from the question naire . RESULTS In 2001 , 36.6 % had achieved asthma control , 23.8 % were partly controlled and 39.6 % uncontrolled . In 2005 , the corresponding figures were 40.2 % , 26.8 % and 33.0 % , respectively , with no difference between the two surveys ( p=0.114 ) . Uncontrolled asthma was more common in women ( p<0.001 in the first and p<0.05 in the second survey ) and smokers ( p<0.01 in the first and p<0.01 in the second survey ) . The use of combination corticosteroid/long-acting bronchodilator inhalers had increased - 34.2 % and 48.2 % , respectively ( p<0.001 ) - and many patients used their inhaled corticosteroids periodically . CONCLUSION In spite of treatment guidelines many patients in Swedish primary care still have insufficient asthma control Objective To determine whether mobile phone based monitoring improves asthma control compared with st and ard paper based monitoring strategies . Design Multicentre r and omised controlled trial with cost effectiveness analysis . Setting UK primary care . Participants 288 adolescents and adults with poorly controlled asthma ( asthma control question naire ( ACQ ) score ≥1.5 ) from 32 practice s. Intervention Participants were central ly r and omised to twice daily recording and mobile phone based transmission of symptoms , drug use , and peak flow with immediate feedback prompting action according to an agreed plan or paper based monitoring . Main outcome measures Changes in scores on asthma control question naire and self efficacy ( knowledge , attitude , and self efficacy asthma question naire ( KASE-AQ ) ) at six months after r and omisation . Assessment of outcomes was blinded . Analysis was on an intention to treat basis . Results There was no significant difference in the change in asthma control or self efficacy between the two groups ( ACQ : mean change 0.75 in mobile group v 0.73 in paper group , mean difference in change −0.02 ( 95 % confidence interval −0.23 to 0.19 ) ; KASE-AQ score : mean change −4.4 v −2.4 , mean difference 2.0 ( −0.3 to 4.2 ) ) . The numbers of patients who had acute exacerbations , steroid courses , and unscheduled consultations were similar in both groups , with similar healthcare costs . Overall , the mobile phone service was more expensive because of the expenses of telemonitoring . Conclusions Mobile technology does not improve asthma control or increase self efficacy compared with paper based monitoring when both groups received clinical care to guidelines st and ards . The mobile technology was not cost effective . Trial registration Clinical Trials NCT00512837 OBJECTIVE Computer-based clinical decision support systems ( CDSSs ) vary greatly in design and function . Using a taxonomy that we had previously developed , we describe the characteristics of CDSSs reported in the literature . METHODS We search ed PubMed and the Cochrane Library for r and omized controlled trials ( RCTs ) published in English between 1998 and 2003 that evaluated CDSSs . We coded each CDSS using our taxonomy . RESULTS 58 studies met our inclusion criteria . The 74 reported CDSSs varied greatly in context of use , knowledge and data sources , nature of decision support offered , information delivery , and workflow impact . Two distinct subsets of CDSSs were seen : patient-directed systems that provided decision support for preventive care or health-related behaviors via mail or phone ( 38 % of systems ) , and inpatient systems targeting clinicians with online decision support and direct online execution of the recommendations ( 18 % ) . 84 % of the CDSSs required extra staffing for h and ling CDSS-related input or output . CONCLUSION Reported CDSSs are heterogeneous along many dimensions . Caution should be taken in generalizing the results of CDSS RCTs to different clinical or workflow setting Background Computerized clinical decision support systems are information technology-based systems design ed to improve clinical decision-making . As with any healthcare intervention with cl aims to improve process of care or patient outcomes , decision support systems should be rigorously evaluated before widespread dissemination into clinical practice . Engaging healthcare providers and managers in the review process may facilitate knowledge translation and uptake . The objective of this research was to form a partnership of healthcare providers , managers , and research ers to review r and omized controlled trials assessing the effects of computerized decision support for six clinical application areas : primary preventive care , therapeutic drug monitoring and dosing , drug prescribing , chronic disease management , diagnostic test ordering and interpretation , and acute care management ; and to identify study characteristics that predict benefit . Methods The review was undertaken by the Health Information Research Unit , McMaster University , in partnership with Hamilton Health Sciences , the Hamilton , Niagara , Haldim and , and Brant Local Health Integration Network , and pertinent healthcare service teams . Following agreement on information needs and interests with decision-makers , our earlier systematic review was up date d by search ing Medline , EMBASE , EBM Review data bases , and Inspec , and review ing reference lists through 6 January 2010 . Data extraction items were exp and ed according to input from decision-makers . Authors of primary studies were contacted to confirm data and to provide additional information . Eligible trials were organized according to clinical area of application . We included r and omized controlled trials that evaluated the effect on practitioner performance or patient outcomes of patient care provided with a computerized clinical decision support system compared with patient care without such a system . Results Data will be summarized using descriptive summary measures , including proportions for categorical variables and means for continuous variables . Univariable and multivariable logistic regression models will be used to investigate associations between outcomes of interest and study specific covariates . When reporting results from individual studies , we will cite the measures of association and p-values reported in the studies . If appropriate for groups of studies with similar features , we will conduct meta-analyses . Conclusion A decision-maker- research er partnership provides a model for systematic review s that may foster knowledge translation and uptake OBJECTIVE 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 AIM To evaluate patient underst and ing of their asthma and determine patient preferences regarding the delivery of asthma care and treatment . METHODS Adults with asthma receiving treatment for mild to moderate asthma were recruited to a two-part study : a qualitative phase using a semi-structured interview schedule followed by a quantitative phase based on a structured interview schedule . All interviews were undertaken face-to-face . SETTING AND SUBJECTS A r and om sample of 40 patients with mild to moderate asthma from seven areas of the UK took part in the qualitative phase of the study . In the quantitative phase , 517 patients on treatment for mild to moderate asthma were interviewed in person by market research ers . This population was achieved using a quota sampling approach that also achieved a representative demographic profile . Initial contact was made in door-to-door calls . Interviews took place in 64 locations across the UK . RESULTS Ninety-one percent ( n=468 ) of respondents felt their asthma was under control , yet two-thirds ( n=339 ) experienced symptoms at least 2 - 3 times a week . Only 24 % ( n=123 ) felt their asthma could improve over time , and 71 % ( n=366 ) received no advice from healthcare professionals on how their asthma might change in the future . Fourteen percent ( n=74 ) of respondents had no ongoing contact with any healthcare professional regarding their asthma . Fifty-eight percent ( n=301 ) were very satisfied with their asthma care , but this dropped to 33 % ( n=173 ) when respondents were shown asthma guidelines regarding what to expect from treatment . Sixty-two percent ( n=318 ) of respondents said their asthma varied at different times of the day , and 86 % ( n=444 ) stated that their asthma varied at different times of the year . Eighty percent ( n=414 ) of respondents had never been provided with a written , personal asthma action plan recommending changes patients could make themselves to prescribed treatment according to symptom severity , though 68 % ( n=353 ) said they would feel comfortable following such a plan . CONCLUSIONS Most patients have low expectations of what can be achieved by asthma management and do not realise their condition can be improved . Many are resigned to the effects of poor asthma control until made aware that guidelines indicate this can be better . Given that many are receptive to the notion of written , personal asthma action plans , the implementation of these , supported by appropriate education , could help patients achieve improved asthma control OBJECTIVE It is difficult to control drug-prescribing behaviour in general practice , despite the development and distribution of guidelines . The purpose of this study was to assess the effect on drug-prescribing behaviour of implementing prescribing guidelines by means of a reactive computer reminder system ( CRS ) . DESIGN Cluster-r and omised controlled trial with an incomplete block design in the south of the Netherl and s : 25 GPs ( 7 GP practice s ) received reminders about antibiotics and asthma/ COPD prescriptions , 28 GPs ( 7 GP practice s ) received reminders about cholesterol prescriptions . Prescription guidelines were integrated into the computerised GP information system . MEASUREMENTS Both performance indicators and prescription volumes were calculated as the main outcome measures . Next to individual volume measure , sum scores were constructed on the volume measures per drug group ( antibiotics , asthma/ COPD and cholesterol ) . RESULTS Variation between GPs turned out to be larger and more skewed than expected . No differences between groups were found for indicators and volumes related to recommendations advocating certain drugs . Although there was a tendency towards clinical ly relevant results for prescription volumes that were supposed to drop , the difference in sum score between the groups was not significant . For antibiotic prescriptions that were supposed to drop , the sum score for the intervention group was 28.2 ( 95 % CI : 20.8 - 44.5 ) prescriptions per 1000 patients per GP , while this was 39.7 ( 95 % CI : 29.7 - 64.1 ) for the control group ( p 0.2 ) . For prescriptions asthma/ COPD that were supposed to drop , the sum score for the intervention group was 1.1 ( 95 % CI : 0.6 - 2.6 ) prescriptions per 1000 patients per GP , while this was 2.2 ( 95 % CI : 1.4 - 4.3 ) for the control group ( p 0.1 ) . On three specific recommendations ( on quinolones for cystitis , corticosteroids for CPOD , and antibiotics for acute sore throat ) significant differences were found . CONCLUSIONS This study turned out to be underpowered due to high inter doctor variation in prescribing behaviour . Nevertheless , computerised reminders sometimes have a favourable effect on restricting certain drugs that are not or no longer indicated in general practice BACKGROUND AND OBJECTIVE To assess the cost-effectiveness of an intervention based on the Global INitiative for Asthma ( GINA ) recommendations as compared to usual care . SUBJECTS AND METHOD Pragmatic , cluster-r and omised trial . Ten pneumologists and 10 general practitioners were r and omised to an intervention or control group , recruiting 98 and 100 asthma patients , respectively . The intervention consisted of an education program and a clinical decision support system ( CDSS ) providing recommendations based on the GINA . The control group was characterized by usual care . Effectiveness was assessed by the health related quality of life as measured by the St. George 's Respiratory Question naire ( SGRQ ) . Costs were computed from the re source consumption recorded during a 12 months follow-up period , and the cost-effectiveness of the intervention was investigated in an incremental analysis . RESULTS The intervention effect on the SGRQ total score was estimated as a 6.8 point reduction ( 95 % confidence interval , 2.5 - 11.1 ; p = 0.0021 ) , and a significant improvement in the SGRQ subscores and in the symptoms-free periods were also observed . From the social perspective , the mean total costs showed savings of -1,022 Euros ( 95 % confidence interval , -2,165 to 122 ; p = 0.0795 ) in intervention group as compared to usual care . The incremental analysis confirmed that the intervention was cost-effective . CONCLUSIONS The implementation of an asthma management program based in GINA recommendations improved the patient 's health related quality of life and was cost-effective as compared to usual care PRIMARY OBJECTIVE To investigate whether computer decision support software used in the management of patients with asthma improves clinical outcomes . RESEARCH DESIGN R and omized controlled trial with practice s each reporting on 30 patients with asthma over a 6 month period . METHODS AND PROCEDURES 447 patients were r and omly selected from practice asthma registers managed by 17 general practice s from throughout the UK . Intervention practice s used the software during consultations with these patients throughout the study while control practice s did not . MAIN OUTCOMES AND RESULTS Practice consultations , acute exacerbations of asthma , hospital contacts , symptoms on assessment and medication use . A smaller proportion of patients within the intervention group initiated practice consultations for their asthma : 34 ( 22 % ) vs 111 ( 34 % ) , odds ratio ( OR ) = 0.59 , 95 % confidence interval ( CI ) ( 0.37 - 0.95 ) ; and suffered acute asthma exacerbations : 12 ( 8 % ) vs 57 ( 17 % ) , OR = 0.43 , 95 % CI = 0.21 - 0.85 six months after the introduction of the computer decision support software . There were no discernable differences in reported symptoms , maintenance prescribing or use of hospital services between the two groups . CONCLUSION The use of computer decision support software that implements guidelines during patient consultations may improve clinical outcomes for patients with asthma OBJECTIVE Translation of evidence -based guidelines into clinical practice has been inconsistent . We performed a r and omized , controlled trial of guideline -based care suggestions delivered to physicians when writing orders on computer workstations . STUDY SETTING Inner-city academic general internal medicine practice . STUDY DESIGN R and omized , controlled trial of 246 physicians ( 25 percent faculty general internists , 75 percent internal medicine residents ) and 20 outpatient pharmacists . We enrolled 706 of their primary care patients with asthma or chronic obstructive pulmonary disease . Care suggestions concerning drugs and monitoring were delivered to a r and om half of the physicians and pharmacists when writing orders or filling prescriptions using computer workstations . A 2 x 2 factorial r and omization of practice sessions and pharmacists result ed in four groups of patients : physician intervention , pharmacist intervention , both interventions , and controls . DATA EXTRACTION / COLLECTION METHODS : Adherence to the guidelines and clinical activity was assessed using patients ' electronic medical records . Health-related quality of life , medication adherence , and satisfaction with care were assessed using telephone question naires . PRINCIPAL FINDINGS During their year in the study , patients made an average of five scheduled primary care visits . There were no differences between groups in adherence to the care suggestions , generic or condition-specific quality of life , satisfaction with physicians or pharmacists , medication compliance , emergency department visits , or hospitalizations . Physicians receiving the intervention had significantly higher total health care costs . Physician attitudes toward guidelines were mixed . CONCLUSIONS Care suggestions shown to physicians and pharmacists on computer workstations had no effect on the delivery or outcomes of care for patients with reactive airways disease Since the relationships between pulmonary function , exercise capacity , and functional state or quality of life are generally weak , a self report question naire has been developed to determine the effect of treatment on quality of life in clinical trials . One hundred patients with chronic airflow limitation were asked how their quality of life was affected by their illness , and how important their symptoms and limitations were . The most frequent and important items were used to construct a question naire evaluating four dimensions : dyspnoea , fatigue , emotional function , and the patient 's feeling of control over the disease ( mastery ) . Reproducibility , tested by repeated administration to patients in a stable condition , was excellent : the coefficient of variation was less than 12 % for all four dimensions . Responsiveness ( sensitivity to change ) was tested by administering the question naire to 13 patients before and after optimisation of their drug treatment and to another 28 before and after participation in a respiratory rehabilitation programme . In both cases large , statistically significant improvements in all four dimensions were noted . Changes in question naire score were correlated with changes in spirometric values , exercise capacity , and patients ' and physicians ' global ratings . Thus it has been shown that the question naire is precise , valid , and responsive . It can therefore serve as a useful disease specific measure of quality of life for clinical trials OBJECTIVE : The goal was to assess the impact of influenza vaccine clinical alerts on missed opportunities for vaccination and on overall influenza immunization rates for children and adolescents with asthma . METHODS : A prospect i ve , cluster-r and omized trial of 20 primary care sites was conducted between October 1 , 2006 , and March 31 , 2007 . At intervention sites , electronic health record-based clinical alerts for influenza vaccine appeared at all office visits for children between 5 and 19 years of age with asthma who were due for vaccine . The proportion of captured immunization opportunities at visits and overall rates of complete vaccination for patients at intervention and control sites were compared with those for the previous year , after st and ardization for relevant covariates . The study had > 80 % power to detect an 8 % difference in the change in rates between the study and baseline years at intervention versus control practice s. RESULTS : A total of 23 418 visits and 11 919 children were included in the study year and 21 422 visits and 10 667 children in the previous year . The majority of children were male , 5 to 9 years of age , and privately insured . With st and ardization for selected covariates , captured vaccination opportunities increased from 14.4 % to 18.6 % at intervention sites and from 12.7 % to 16.3 % at control sites , a 0.6 % greater improvement . St and ardized influenza vaccination rates improved 3.4 % more at intervention sites than at control sites . The 4 practice s with the greatest increases in rates ( ≥11 % ) were all in the intervention group . Vaccine receipt was more common among children who had been vaccinated previously , with increasing numbers of visits , with care early in the season , and at preventive versus acute care visits . CONCLUSIONS : Clinical alerts were associated with only modest improvements in influenza vaccination rates |
1,225 | 16,344,285 | Carbapenems were associated with fewer treatment modifications , including addition of glycopeptides , than ceftazidime or other comparators .
No significant differences were demonstrated with paucity of data for all-cause mortality .
Empirical use of carbapenems entails fewer treatment modifications , but an increased rate of pseudomembranous colitis .
Ceftazidime , piperacillin/tazobactam , imipenem/cilastatin and meropenem appear to be suitable agents for monotherapy | OBJECTIVES Early , empirical broad-spectrum antibiotic treatment is the established practice for febrile neutropenia .
Several beta-lactams are accepted for monotherapy .
We asked whether patients ' outcomes are influenced by the chosen beta-lactam . | In a prospect i ve , r and omized , controlled trial , we compared sulbactam/cefoperazone with imipenem as empirical monotherapy for febrile , granulocytopenic patients ; 101 patients received sulbactam/cefoperazone ( 2 g/4 g every 12 hours ) and 102 patients received imipenem ( 500 mg every 6 hours ) . Documented infections were present in 40 % of patients treated with sulbactam/cefoperazone ( 40 of 101 ) and in 39 % of patients receiving imipenem ( 40 of 102 ) . The number of pretherapy gram-positive pathogens ( 52 isolates ) was twice the number of pretherapy gram-negative pathogens ( 26 isolates ) . The overall favorable clinical response rates for sulbactam/cefoperazone ( 91 of 103 patients , or 88 % ) and imipenem ( 84 of 104 patients , or 81 % ) were similar . Both drugs were generally well tolerated . However , diarrhea occurred more often in patients treated with sulbactam/cefoperazone ( 31 of 101 patients , or 31 % , vs. 15 of 102 patients , or 15 % ; P = .007 ) , while seizures developed only in patients receiving imipenem ( 0 of 101 patients vs. 3 of 102 patients , or 3 % ) . Superinfections developed in 16 % of patients in both study groups but were infrequently caused by beta-lactam-resistant gram-negative bacilli ( two cases with sulbactam/cefoperazone therapy and six cases with imipenem ) . These results support the efficacy and safety of either sulbactam/cefoperazone or imipenem as empirical monotherapy for febrile granulocytopenic patients OBJECTIVE : To compare the efficacies of cefepime and ceftazidime as empiric therapy during the management of fever in cancer patients with chemotherapy-induced neutropenia . METHODS : A prospect i ve , double-blind , r and omized study of cefepime 2 g every eight hours and ceftazidime 2 g every eight hours was performed in 276 adult neutropenic ( absolute neutrophil count < 500/mm3 ) cancer patients with fever . RESULTS : Median duration of neutropenia was five days . Sixty-one percent ( n = 188 ) of the patients were evaluable . Treatment was successful in 57 % ( 58/101 ) of cefepime-treated patients and 60 % ( 52/87 ) of ceftazidime-treated patients ( 95 % CI −18 to 12 ; p = 0.77 ) . Bacteremic clearance occurred in 71 % ( 12/17 ) of cefepime-treated patients and 40 % ( 6/15 ) of ceftazidime-treated patients ( p = 0.3 ) . Both drugs were well tolerated . CONCLUSIONS : Cefepime appears to be as effective as ceftazidime in the initial treatment of febrile episodes in adult cancer patients with chemotherapy-associated neutropenia of modest duration BACKGROUND With the availability of new broad-spectrum antibiotics , initial therapy with a single agent has become an alternative to classic combinations , especially beta-lactam antibiotics plus aminoglycosides , in the management of febrile neutropenic cancer patients . PROCEDURE Since January 1994 , monotherapy has been used for empiric initial treatment at our center . The aim of this prospect i ve r and omized study is to compare the efficacy of cefepime ( CFP ) , a new fourth-generation cephalosporin , and ceftazidime ( CFZ ) as empirical monotherapy of febrile neutropenic patients with solid tumors . From January 1998 to November 1998 , 63 episodes of fever and neutropenia occurring in 33 children with solid tumors including lymphomas , were r and omized to receive treatment with either CFP or CFZ . The patients were analyzed for leukocyte count and absolute neutrophil count ( ANC ) at entry , days in fever , neutropenia and hospitalization , and side effects of drugs . Success with or without modifications of the initial antibiotic was defined as survival through neutropenia ; failure was death due to infection . RESULTS In our study group , with a median age of 7 [ (1/12)-14 ] years , CFP was administered in 32 , and CFZ in 31 episodes . An infection was documented microbiologically in eight episodes ( 25 % ) in the CFP arm and in nine episodes ( 29 % ) in the CFZ arm . The success rate with initial empiric monotherapy was 62.5 % in the CFP arm and 61.3 % in the CFZ arm respectively ( P > 0.05 ) . The total success rate ( success with or without modification ) was 100 % in both arms . No major adverse effects were observed in either groups . CONCLUSION CFP is as effective and safe as CFZ for the empirical treatment of febrile episodes in neutropenic patients with solid tumors Abstract A total of 101 cancer patients with 121 febrile neutropenia episodes were r and omised to receive empirical treatment with i.v . meropenem ( 1 g/8 h ) or ceftazidime ( 2 g/8 h ) . After 3 days , 89 % of patients were on unmodified therapy in the meropenem group , compared with 83 % in the ceftazidime group . Of the evaluable episodes ( n=106 ) , the success rate with unmodified empirical therapy until the end of the treatment course was slightly higher with meropenem than with ceftazidime ( 48 % vs 38 % , P=0.39 ) . Furthermore , initial success with further infections was observed in 22 % of episodes treated with meropenem and in 13 % of episodes treated with ceftazidime . Glycopeptides were used as first modification in 28 % and 39 % of meropenem and ceftazidime recipients , respectively . Both treatments were well tolerated and there were no reports of drug-related nausea/vomiting or seizures . No significant differences in response rate or in tolerability were observed when analysing only the first febrile episodes . In conclusion , meropenem seems to be as efficacious and well tolerated as ceftazidime and may be associated with a lesser requirement for the addition of glycopeptides Serum procalcitonin ( PCT ) levels have been proposed as a new discriminative marker for bacterial and fungal infections . We analysed the diagnostic relevance of PCT in febrile episodes of neutropenic adult patients after haematopoietic stem cell transplantation ( HSCT ) . PCT was determined prospect ively in 92 febrile episodes , classified according to the final diagnosis as : neutropenic fever of unknown origin ( n = 51 ) , microbiological ( n = 26 ) or clinical ( n = 5 ) documented infection and non‐infectious febrile episodes ( n = 10 ) . On first day of fever , mean ( ±SD ) PCT level was 0·3 ng/ml ( 0·2 ) in neutropenic fever of unknown origin , 0·5 ng/ml ( 0·7 ) in microbiologically confirmed infections , 0·2 ng/ml ( 0·2 ) in clinical ly documented infections and 1·7 ( 4·2 ) in non‐infectious fever ( P = not significant ) . Five days after the antibiotic therapy was started , fever persisted in 29 neutropenic episodes ( 32 % ) . Cases that were eventually diagnosed with invasive aspergillosis had PCT values significantly higher [ 10·1 ng/ml ( 6·7 ) ] than all remaining groups ( P = 0·027 ; Kruskal – Wallis ) . Our analysis indicates that the PCT level on first day of fever did not facilitate the differential diagnosis of neutropenic febrile episode . However , when fever persisted for more than 5 d , PCT values ≥3 ng/ml had a high sensitivity and specificity for the diagnosis of invasive aspergillosis This open , comparative , r and omized , multicentre equivalence study compared cefepime 2 g bd and imipenem-cilastatin 1 g tds ( 50 mg/kg/day ) as empirical monotherapy for febrile episodes in a homogeneous cohort of cancer patients with short duration neutropenia following chemotherapy for solid tumour , lymphoma or myeloma . The study was conducted in 17 French anti-cancer centres in 1995 and 1996 . Response to monotherapy was assessed 7 days after treatment and was based on resolution of fever and signs and symptoms , eradication of pathogens , absence of new infection , relapse , and death of infectious origin , without addition of other antibiotics . Patients were treated for a minimum of 4 days . Of the 400 episodes r and omized , 344 ( 86 % ) were evaluable for efficacy . Patient characteristics were comparable between treatment groups . Success of monotherapy was observed in 79 % of episodes with cefepime and 72 % with imipenem-cilastatin ( equivalence , P < 0.0001 ) . The response rate for microbiologically documented infections was 66 % with cefepime and 61 % with imipenem-cilastatin ( bacteraemic episodes : 63 % for cefepime ; 44 % for imipenem-cilastatin ) . A second antibiotic ( usually a glycopeptide ) was added in 20 % and 21 % of the cases , respectively . Overall , the response to therapy , with or without an additional antibiotic , was 95 % ( cefepime ) and 90 % ( imipenem-cilastatin ) . Survival was similar in both groups ( 95 % and 98 % , respectively ) . Cefepime treatment was better tolerated , with 9 % of the patients experiencing related intercurrent events compared with 19 % in the imipenem-cilastatin group ( P = 0.003 ) . Nausea/vomiting was significantly more frequent in the imipenem-cilastatin group ( 15 % ) than in the cefepime group ( 5 % ; P = 0.001 ) . Cefepime monotherapy was as effective as , and better tolerated than , imipenem-cilastatin in the empirical treatment of fever during short duration neutropenia Background . Monotherapy with cefepime or ceftazidime is an effective alternative to combination therapy for the treatment of febrile neutropenic adult cancer patients . We compared the efficacy and safety of cefepime and ceftazidime as empiric monotherapy of febrile neutropenia in children with cancer . Material s and methods . A prospect i ve , open label , r and omized , comparative study in pediatric cancer patients was conducted at Chang Gung Children ’s Hospital from January 1 , 2000 , to April 15 , 2001 . Patients with fever and neutropenia ( absolute neutrophil count of ≤500/mm3 ) were r and omized to receive either intravenous cefepime or ceftazidime ( 50 mg/kg/dose as two or three doses daily ) . Febrile episodes were classified as microbiologically documented infection , clinical ly documented infection or unexplained fever . Clinical response to therapy was classified as success and failure . Results . Ninety-five pediatric cancer patients with 120 febrile neutropenic episodes were r and omized to receive empiric treatment with cefepime or ceftazidime . After 72 h of treatment , 82.8 % ( 48 of 58 ) of the eligible patients in the cefepime group continued with unmodified therapy , compared with 87.9 % ( 51 of 58 ) in the ceftazidime group . The neutrophil count was < 100/mm3 at r and omization for 76 % of the patients in the cefepime group and 83 % of those in the ceftazidime group ; the median duration s of neutropenia ( < 500/mm3 ) were 8.5 and 6.5 days , respectively . Of the 96 evaluable episodes the overall success rate with unmodified empiric therapy until the end of the treatment course in the cefepime group was comparable with that in the ceftazidime group ( 69%vs . 71 % , P = 0.95 ) . The response rate after glycopeptides were added to the regimens was 79.2 % for the cefepime group and 77.1 % for the ceftazidime group . The bacterial eradication rate was 33 % for the cefepime group and 20 % for the ceftazidime group ( P = 0.85 ) , and the rates of new infections were 10.4%vs . 4.2 % ( P = 0.67 ) , respectively . Both study drugs were well-tolerated . Three ( 6.4 % ) patients in the cefepime group and 2 ( 4.3 % ) patients in the ceftazidime group died . Conclusion . Cefepime appeared to be as effective and safe as ceftazidime for empiric treatment of febrile episodes in neutropenic pediatric cancer patients 1998 , a consensus meeting was held in Miyazaki , Japan , to develop an approach to management of febrile neutropenia ( FN ) . The K‐HOT study group decided to examine whether this proposal was applicable to clinical practice in a multicenter study . Patients who developed fever with neutrophil counts < 1,000/μL were r and omized to receive either a single antibiotic , cefepime or one of the carbapenems , or a combination of cefepime and an aminoglycoside . Patients who became afebrile within the first 3 days were continued on the same treatment . Patients who remained febrile were switched to a combination regimen if they were r and omized to receive a single agent , and patients on combination medication were changed from cefepime to another cephalosporin . A total of 165 patients were entered into the trial . One hundred fifty‐three patients were evaluable for response . The average age was 52 years , and 70 % of the patients had acute leukemia . Severe neutropenia , defined as < 100/μL at the time of FN , was seen in 62 % of the patients on entry and during the course of treatment 71 % of patients experienced neutrophil counts of < 100/μL. Microbiologically documented infection was seen in 6.5 % for monotherapy , and 10.5 % for a combination treatment , and fever of unknown origin occurred in 75.3 % and 59.2 % of the patients in each regimen , respectively . Excellent to good response was seen in two‐thirds of the patients in all treatment groups . Adverse events were minimal , and three early deaths were observed at days 9 , 16 , and 16 among patients treated with a single antibiotic and three in the combination regimen group at days 14 , 15 , and 20 . These results indicate that cefepime or a carbapenem alone is as effective as a combination of cefepime and an aminoglycoside for treating FN . Am . J. Hematol . 71:248–255 , 2002 . © 2002 Wiley‐Liss , BACKGROUND Fluoroquinolone prophylaxis during neutropenia in patients with cancer has been associated with decreased incidence of gram-negative bacteremia . Bacterial antimicrobial resistance is likely to cause a progressive lack of efficacy of fluoroquinolones , but no convincing evidence from clinicoepidemiologic observations has proved this hypothesis . METHODS This prospect i ve observational study assessed the impact of discontinuing fluoroquinolone prophylaxis on the incidences of fever and bacteremia and on mortality among patients with neutropenia , after chemotherapy for hematologic malignancies . RESULTS After a 12-month baseline period of levofloxacin prophylaxis , a period of discontinuation of fluoroquinolone prophylaxis was planned but was stopped prematurely after 9 neutropenic episodes over 3 weeks , because the mortality rate ( 33.3 % ) was higher than that with routine fluoroquinolone prophylaxis ( 2.9 % ) ( odds ratio [ OR ] , 16.6 ; 95 % confidence interval [ CI ] , 3.6 - 77.2 ) . Fewer patients had gram-negative bacteremia during the baseline period ( 4.8 % ; n=15 ) than during the discontinuation period ( 44.4 % ; n=4 ) ( OR , 16.9 ; 95 % CI , 4.1 - 70.0 ) . After levofloxacin therapy was reintroduced , the incidence of gram-negative bacteremia and the mortality rate were comparable to those during the first period . Escherichia coli isolated during the discontinuation period was susceptible to levofloxacin in vitro , whereas all E. coli isolates isolated during both prophylaxis periods were resistant . Bloodstream infections were caused by a single agent when the patient had received levofloxacin prophylaxis , whereas most cases of gram-negative bacteremia were polymicrobial after discontinuation . CONCLUSIONS These findings suggest that , despite increasing rates of antimicrobial resistance , levofloxacin prophylaxis during neutropenia may have a beneficial impact on morbidity and infection-related mortality . Continued monitoring of the rate of gram-negative bacteremia is warranted for timely detection of the loss of efficacy of fluoroquinolone prophylaxis PURPOSE Febrile neutropenia remains a potentially life-threatening complication of anticancer chemotherapy , but some patients are at low risk for serious medical complications . The purpose of this study was to develop an internationally vali date d scoring system to identify these patients . MATERIAL S AND METHODS Febrile neutropenic cancer patients were observed in a prospect i ve multinational study . Independent factors assessable at fever onset , predicting low risk of complications , on a r and omly selected derivation set , were assigned integer weights to develop a risk-index score , which was subsequently tested on a validation set . RESULTS On the derivation set ( 756 patients ) , predictive factors were a burden of illness indicating absence of symptoms or mild symptoms ( weight , 5 ; odds ratio [ OR ] , 8.21 ; 95 % confidence interval [ CI ] , 4.15 to 16.38 ) or moderate symptoms ( weight , 3 ; OR , 3.70 ; 95 % CI , 2.18 to 6.29 ) ; absence of hypotension ( weight , 5 ; OR , 7.62 ; 95 % CI , 2.91 to 19.89 ) ; absence of chronic obstructive pulmonary disease ( weight , 4 ; OR , 5 . 35 ; 95 % CI , 1.86 to 15.46 ) ; presence of solid tumor or absence of previous fungal infection in patients with hematologic malignancies ( weight , 4 ; OR , 5.07 ; 95 % CI , 1.97 to 12.95 ) ; outpatient status ( weight , 3 ; OR , 3.51 ; 95 % CI , 2.02 to 6.04 ) ; absence of dehydration ( weight , 3 ; OR , 3.81 ; 95 % CI , 1.89 to 7.73 ) ; and age less than 60 years ( weight , 2 ; OR , 2.45 ; 95 % CI , 1.51 to 4.01 ) . On the validation set , a Multinational Association for Supportive Care in Cancer risk-index score > /= 21 identified low-risk patients with a positive predictive value of 91 % , specificity of 68 % , and sensitivity of 71 % . CONCLUSION The risk index accurately identifies patients at low risk for complications and may be used to select patients for testing therapeutic strategies that may be more convenient or cost-effective The efficacies of meropenem , a novel carbapenem , and ceftazidime , as empirical therapy of febrile neutropenic patients , were compared in a prospect i ve , r and omized clinical trial . One hundred and twelve adult patients were given meropenem 1 g tds iv for 153 episodes of fever , while 109 patients received ceftazidime 2 g tds iv for 151 episodes . All patients survived the first 3 days of therapy and , by the end of the treatment courses , 67 ( 44 % ) episodes had responded to meropenem , compared with 62 ( 41 % ) to ceftazidime . Eighty ( 53 % ) episodes initially treated with ceftazidime and 63 ( 41 % ) episodes treated with meropenem were considered to have failed treatment because it was thought necessary to administer additional antibacterial agents ; however , modifications were made twice as often because of fever that persisted beyond 2 - 3 days than because of obvious causes of failure such as persistent infection . Three patients in the ceftazidime group and five in the meropenem group died . Meropenem was well tolerated , with no reports of nausea or toxicity to the central nervous system . Although ceftazidime was shown in the present study to be as effective as meropenem , the broader spectrum of activity of meropenem against Gram-positive cocci suggests that it might be more appropriate as empirical therapy of febrile neutropenic patients who are at high risk of acquiring infections caused by these bacteria This trial assessed the efficacy and safety of meropenem versus ceftazidime as empirical monotherapy for febrile neutropenia in paediatric cancer patients . In a prospect i ve r and omized study , 172 evaluable febrile episodes in the meropenem arm and 170 episodes in the ceftazidime arm were analysed for the clinical and microbiological response dependent on the kind of infection . About half the episodes were classified as fever of unknown origin ( FUO ) and the remainder as microbiologically or clinical ly documented infections . The most frequently documented infections in both arms were bacteraemias ( 22.1 versus 26.5 % ) , predominantly caused by Gram-positive organisms ( 57.9 versus 71.1 % ) . The success rate of the initial monotherapy differed significantly between the two arms and was 55.8 % in the meropenem and 40.0 % in the ceftazidime arm ( P = 0.003 ) . In addition , a significantly longer duration of fever and of antimicrobial therapy was observed in the ceftazidime arm than in the meropenem arm ( median 5 versus 4 days , P = 0.022 , and 7 versus 6 days , P = 0.009 , respectively ) . With respect to the kind of infection , differences between the two arms were significant only in episodes classified as FUO but not in documented infections . In both arms , side effects were minimal . Despite the greater response rate for meropenem in FUO , the fact that ceftazidime has been proven to be as effective as meropenem in documented infections in the present study suggests that both drugs are useful as empirical monotherapy in febrile paediatric cancer patients Between July 1993 and September 1996 , 107 consecutive febrile episodes in 83 neutropenic cancer patients with a median age of 41 years were r and omized to treatment either with piperacillin/tazobactam 4.5 g every 8 h i.v . or ceftazidime 2 g every 8 h plus amikacin 15 mg/kg i.v . per day . In the case of fever > 38 ° C 48 h after initiation of the antibiotic therapy , vancomycin 500 mg every 6 h i.v . was added . The study population was at serious risk of a poor outcome , since 67 % of the patients had leukemia or lymphoma , 19 % of the febrile events occurred after autologous bone marrow or blood stem cell transplantation , the median total duration of neutropenia was 16 days , and the median neutrophil count at study inclusion was 0.09 × 109/l . The two patient groups were comparable in terms of risk factors . Bacteremia was found in 37 % , other microscopically documented infections in 16 % , and clinical ly documented infections in 26 % of the febrile episodes . Most ( 96 ) febrile episodes were evaluable for response . No significant difference was found between piperacillin/ tazobactam and ceftazidime plus amikacin in terms of success rate ( 81 % versus 83 % ) , empirical addition of vancomycin ( 42 % versus 38 % ) , median time to fever defervescence ( 3.3 versus 2.9 days ) or median duration of antibiotic therapy ( 7.2 versus 7.4 days ) . No patient died from the infection . Both antibiotic regimens were well tolerated , the study treatment being stopped only in 1 patient because of toxicity ( cutaneous allergy to piperacillin/tazobactam ) . On the basis of the 107 febrile events encountered , we conclude that piperacillin/tazobactam is a safe and effective monotherapy . To define the definitive value of piperacillin/ tazobactam as a monotherapy for febrile neutropenic patients a large r and omized trial is warranted PURPOSE To compare the efficacy of ceftazidime and imipenem monotherapy for fever and neutropenia , and to determine whether fewer antimicrobial modifications ( additions or changes ) are required by the broader-spectrum agent , imipenem . PATIENTS AND METHODS Adult and pediatric patients undergoing chemotherapy for solid tumors , leukemias , or lymphomas were r and omized to receive open-label ceftazidime or imipenem on presentation with fever and neutropenia . Success with or without modifications of the initial antibiotic was defined as survival through neutropenia ; failure was death due to infection . Comparisons were based on numbers of modifications made to each monotherapy during the course of neutropenia , in patients stratified as having unexplained fever or a documented infection . RESULTS Among 204 ceftazidime and 195 imipenem recipients , the overall success rate with or without modification was more than 98 % , regardless of initial antibiotic regimen . Modifications occurred in half of all episodes , primarily in patients with documented infections on either monotherapy . Antianaerobic agents were more frequently added to ceftazidime ( P < .001 ) , but addition of other antibiotics , including vancomycin and aminoglycosides , was similar between the two monotherapy groups . Imipenem therapy was associated with significantly greater toxicity , manifested by Clostridium difficile-associated diarrhea and by nausea and vomiting , which required discontinuation of imipenem in 10 % of recipients . CONCLUSION Ceftazidime and imipenem are both effective in the management of fever and chemotherapy-related neutropenia , provided that modifications are made in response to clinical and microbiologic data that emerge during the course of neutropenia . Imipenem , despite its broader antimicrobial spectrum , does not significantly decrease the overall need for antibiotic modifications and is more often complicated by gastrointestinal toxicity The objective of the presented prospect i ve , r and omized study was to compare the efficacy of empirical antimicrobial monotherapy with piperacillin/tazobactam ( PIP/TAZ ) to cefepime ( CEFP ) for treatment of infections in neutropenic patients . From a total of 102 febrile episodes 100 were evaluable . The most frequent microorganisms were gram-negative , documented in 22 % vs. 24 % of the febrile episodes ( gram-positives 18 % vs. 16 % , fungi 2 % vs. 4 % ) . The response rate was similar with 22/51 ( 43 % ) of episodes treated with PIP/TAZ vs. 19/49 ( 39 % ) with CEFP . Of the different infection types classified at the end of the febrile episodes , patients with fever of unknown origin ( FUO ) and primary bacteremias showed the best initial responses with 25/44 ( 57 % ) and 11/22 ( 50 % ) . Lower initial response rates were found in pneumonias with totally 3/13 ( 23 % ) and other clinical ly documented infections with 2/21 ( 10 % ) , without any difference between both groups . Gram positive infections showed a higher response with PIP/TAZ than with CEFP ( 4/9 vs. 0/8 ) , gram negative responded less frequently ( 3/11 vs. 7/13 ) . The median time until persistent defervescence was equal in both groups ( 2.5 vs. 2 days ) , likewise the response rates after the different steps of therapy modifications ( change to imipenem or ceftazidim , or addition of gentamycin , vancomycin or amphotericin B ) . Totally , 96 % of febrile episodes responded in both therapy arms . Overall , we found no significant differences in efficacy between the two therapeutic regimens . In conclusion , PIP/TAZ as well as CEFP might be a sufficient initial therapy for febrile neutropenia , but further r and omized trials with larger patient numbers are necessary In this Swedish multicentre study we compared the efficacy of meropenem with ceftazidime for treatment of febrile neutropenia . 192 patients were r and omized and the number of evaluable patients was 92 in the meropenem group and 95 in the ceftazidime group . 40 ( 43 % ) patients in the meropenem arm and 49 ( 52 % ) in the ceftazidime arm had acute leukaemia . 56 ( 61 % ) and 52 ( 55 % ) patients respectively had a neutrophil count of < 0.1 x 10(9)/l at r and omization and the median duration of neutropenia was 6.5 and 8 d , respectively . Thirty-one ( 34 % ) and 28 ( 29 % ) patients had a microbiologically defined infection , 14 ( 15 % ) and 17 ( 18 % ) a clinical ly defined infection and the remaining 47 ( 51 % ) and 50 ( 53 % ) had unexplained fever . After 72 h of treatment , 46 ( 50 % ) patients in the meropenem arm and 53 ( 56 % ) patients in the ceftazidime arm were alive on unmodified monotherapy . 42 ( 46 % ) and 47 ( 49 % ) of these completed the study on monotherapy alone . Only 2 patients ( 2 % ) in each arm had to stop treatment owing to allergic reactions . None of the observed differences were statistically significant and we therefore conclude that meropenem was an effective and safe alternative to ceftazidime for empiric treatment of fever during neutropenia With the availability of new , broad-spectrum antibiotics , initial therapy with a single agent has become an alternative to classic combinations in the management of febrile , neutropenic cancer patients . The aims of this study were to compare the efficacy of ceftazidime and imipenem as empirical monotherapy of febrile episodes in neutropenic patients , and to examine the frequency with which second-line antibiotics ( amikacin , vancomycin , or both ) were required . A prospect i ve clinical trial was carried out in a single centre . Eligible patients with solid tumours or lymphoma were r and omised to receive monotherapy with ceftazidime or imipenem . In the event of no response , amikacin and /or vancomycin were added in 48 - 72 h intervals ( sequentially , or according to clinical or microbiological data ) . Efficacy was evaluable for 111 assessable episodes . Median neutrophil count at entry was 100 cells/microliters and median duration of neutropenia was 4 days . Febrile episodes were classified as microbiologically ( 34 % ) or clinical ly documented ( 42 % ) , and fever of unknown origin ( 24 % ) . Gram-negative infections ( 57 % ) predominated over gram-positive isolates ( 30 % ) . The overall success rate with monotherapy ( 69 % versus 70 % ) , or with modification ( 20 % versus 23 % ) were equivalent for ceftazidime and imipenem ( P = 0.75 ) . The mortality in this series was 5 % . Single-agent therapy with either ceftazidime or imipenem is effective for the empirical treatment of febrile episodes in neutropenic patients with solid tumours . Early addition of amikacin and /or vancomycin resolves most failures of the first step A prospect i ve , open label , r and omized , multicentre study was conducted , comparing the efficacy and safety of cefepime with that of imipenem-cilastatin for the management of febrile neutropenia in patients with haematological malignancies . Furthermore , the safety of early discontinuation of antibiotic therapy in patients with fever of undetermined origin ( FUO ) was assessed . A total of 180 patients with 207 febrile episodes were r and omized at start of fever ( 105 episodes for cefepime and 102 episodes for imipenem ) . The 2 groups were comparable in terms of age , gender , underlying malignancy , prior transplantation , and presence of central venous catheters . All patients were neutropenic at inclusion with median absolute neutrophil count ( ANC ) 0.1 × 109/l(range 0–1 × 109/l ) , and ANC ≤0.1 × 109/l in 77 % of included patients . The mean duration of neutropenia , with ANC < 0.5 × 109/l was 6.2 d. Febrile episodes were classified as microbiologically documented infection ( 47 % ) , FUO ( 43 % ) , or clinical ly documented infection ( 10 % ) . At final evaluation 1–2 weeks after completion of antibiotic therapy , monotherapy success rates were 40 % and 51 % in the cefepime and imipenem-cilastatin groups respectively ( p=0.33 ) . The 4-week overall mortality rate was 5 % . Three ( 2 % ) of the cefepime treated patients and 4 ( 3 % ) of the imipenem-cilastatin treated patients died as a result of infection . Adverse events directly related to antibiotic treatment were uncommon and did not differ between groups . Early discontinuation of antibiotic therapy in 31 patients with FUO 48 h after defervescence was not associated with an increased rate of fever relapse or mortality compared with a subgroup of 29 patients where therapy was continued PURPOSE To compare meropenem , a carbapenem antibiotic , with ceftazidime for the empirical treatment of patients with febrile neutropenia . PATIENTS AND METHODS A prospect i ve , double-blind , r and omized clinical trial was conducted at medical centers in North America and the Netherl and s. A total of 411 cancer patients ( 196 treated with meropenem and 215 treated with ceftazidime ) , who had 471 episodes of fever , participated in the trial . For each neutropenic episode , patients were allocated at r and om to receive intravenous administration of meropenem ( 1 g every 8 hours ) or ceftazidime ( 2 g every 8 hours ) . Treatment could be modified at any time . Key end points were clinical and bacteriologic outcomes , eradication of infecting organism , and adverse events . RESULTS The rate of successful clinical response at the end of therapy was significantly higher for patients treated with meropenem than for those on ceftazidime for all episodes ( 54 % v 44 % , respectively ) and for episodes of fever of unknown origin ( 62 % v 46 % , respectively ) , but differences between groups were not statistically significant for clinical ly defined or microbiologically defined infections . Meropenem was significantly more effective than ceftazidime in severely neutropenic ( < /= 100 cells/microliter ) patients ( 55 % v 43 % , respectively ) , bone marrow transplant patients ( 73 % v 27 % , respectively ) , and patients given antibiotic prophylaxis before study entry ( 71 % v 52 % , respectively ) . Common adverse effects of meropenem and ceftazidime therapy were rash , diarrhea , and nausea and vomiting . CONCLUSION Monotherapy with meropenem represents a suitable choice for initial empirical antibiotic therapy for febrile episodes in neutropenic cancer patients A total of 535 evaluable febrile episodes in neutropenic patients were r and omly assigned to treatment with ticarcillin-clavulanate plus vancomycin ( TV ) , ceftazidime plus vancomycin ( CV ) , or all three antibiotics ( TCV ) . The TCV regimen was significantly more effective than TV , considering all evaluable episodes , documented infections , gram-negative infections , and infections in patients with persistent severe neutropenia ( less than 100 neutrophils/mm3 ) . The results with CV were intermediate between TV and TCV . The toxicities were similar with all three regimens and consisted primarily of skin rashes . The TCV regimen is effective for empiric therapy of fever in neutropenic patients and probably should be utilized in preference to CV or TV , although its superiority over CV in this study was inconclusive BACKGROUND Neutropenic patients with cancer are traditionally treated with empiric antibiotic combinations when they become febrile . The availability of broad-spectrum antibiotics such as ceftazidime and imipenem has made it possible to initiate therapy with a single agent ( monotherapy ) . The objectives of this trial were to compare ceftazidime and imipenem as single agents for the therapy of febrile episodes in neutropenic patients and to ascertain whether the addition of an aminoglycoside ( amikacin ) to either of these agents would provide an advantage . METHODS A prospect i ve clinical trial was conducted in which eligible neutropenic patients with cancer were r and omized to one of four treatment arms : ceftazidime alone ; imipenem alone ; ceftazidime plus amikacin ; and imipenem plus amikacin . Efficacy analysis was done for 750 assessable episodes . A multivariate logistic-regression analysis was also performed to examine the unique contribution of various prognostic factors . RESULTS The overall response rates were 76 % with imipenem plus amikacin , 72 % with imipenem , 71 % with ceftazidime plus amikacin , and 59 % with ceftazidime alone . Single-organism gram-positive infections occurred in 101 of 750 episodes . Without a change in antibiotics , the response rates were 50 % with imipenem , 40 % with imipenem plus amikacin , 39 % with ceftazidime plus amikacin , and 38 % with ceftazidime . Most responded to vancomycin or other antibiotics , and the mortality associated with gram-positive infections was only 5 % . Regardless of the antibiotic regimen , the majority of uncomplicated gram-negative infections responded to therapy and the majority of complicated gram-negative infections failed to respond . Multivariate logistic-regression analysis showed that recovery of the neutrophil count was the most favorable prognostic factor in a patient 's response to infection , whereas the presence of gram-positive infection , acute leukemia , pulmonary or enteric infection , and therapy with ceftazidime were unfavorable factors . CONCLUSIONS Single-agent therapy with imipenem is as effective as more conventional combination antibiotic therapy for the empirical treatment of febrile episodes in neutropenic patients with cancer An open-label , r and omized comparative study was conducted to evaluate the efficacy and safety of cefepime ( 2.0 g q. 8 h ) and ceftazidime ( 2.0 g q. 8 h ) in the empiric therapy of febrile neutropenic patients . A total of 45 eligible febrile episodes were r and omized ( 1:1 ) to be treated with the study regimen . Nineteen febrile episodes treated with cefepime and 22 febrile episodes treated with ceftazidime were evaluable for efficacy . The two groups were comparable in terms of age , sex , height , weight , underlying neoplasm , number of pretherapy neutrophil , duration of neutropenia and types of infections . The overall therapeutic success rate of the cefepime group ( 53 % ) was comparable to the ceftazidime group ( 50 % ) . It did not differ significantly ( 95 % confidence interval : –0.28 to 0.34 , p = 0.85 ) . Eighty-eight percent of pathogens in each group were bacteriologically eradicated . The safety profile was similar in both groups . No patients in either group discontinued the therapy because of adverse events . None ( 0 % ) of the cefepime patients and 2 ( 9 % ) of the ceftazidime patients died of infection . The results of this study suggest that cefepime is an effective and safe agent in the empiric therapy of febrile episodes in neutropenic patients The objective of the current study was to compare the efficacy and safety of imipenem and cefepime in the treatment of adult patients with cancer who had fever and neutropenia requiring hospitalization according to Infectious Disease Society of America criteria |
1,226 | 25,164,590 | Based on current literature , intravenous sodium bicarbonate does not seem to be more efficient than saline for the prevention of contrast-media-induced AKI , cardiac surgery-associated AKI , pigment nephropathy or septic AKI .
However , some cohort studies or prospect i ve r and omized trials did track and report serious adverse events , such as higher rates of AKI or higher in-hospital mortality . | Abstract The best “ treatment ” of acute kidney injury ( AKI ) is prevention .
Patients who are at high risk of AKI should have an assessment of their volume status and receive appropriate volume expansion .
The most effective type of intravenous fluid remains unclear .
Innumerable studies have compared sodium bicarbonate and isotonic saline and have combined fluid hydration with pharmacological interventions , particularly N-acetyl-cysteine . | Introduction Cardiac-surgery-associated-acute-kidney-injury ( CSA-AKI ) is associated with increased morbidity and mortality . Recent data from patients undergoing on-pump coronary artery bypass grafting suggest that a perioperative infusion of sodium-bicarbonate may decrease the incidence of CSA-AKI . The present study aims to analyze the renoprotective effects of a 24h infusion of sodium-bicarbonate in a large , heterogeneous group of cardiac surgical patients Methods Starting in 4/2009 , all patients undergoing cardiac surgery at our institution were enrolled in a prospect i ve trial analyzing the relationship between preoperative cerebral oxygen saturation and postoperative organ dysfunction . We used this prospect ively sample d data set to perform a cohort analysis of the renoprotective efficiency of a 24h continuous perioperative infusion of sodium-bicarbonate on the incidence of CSA-AKI that was routinely introduced in 7/2009 . After exclusion of patients with endstage chronic kidney disease , off-pump procedures , and emergency cases , perioperative changes in renal function were assessed in 280 patients treated with a perioperative infusion of 4 mmol sodium-bicarbonate / kg body weight in comparison with a control cohort of 304 patients enrolled from April to June in this prospect i ve cohort study .Postoperative changes in urine flow , plasma creatinine , estimated creatinine clearance , and the need for renal replacement therapy were determined according to AKI injury network criteria . Concomitantly , hemodynamics , treatments , complications , and clinical outcomes were recorded . Univariate statistical analyses were performed para- and nonparametrically , as appropriate . Results With the exception of a lower prevalence of a history of myocardial infa rct ion and a lower preoperative use of intravenous heparin in the bicarbonate-group , no significant between group differences in patient demographics , surgical risk , type , and duration of surgery were observed . Patients in the bicarbonate group had a lower mean arterial blood pressure after induction of anesthesia , needed more fluids , more vasopressors , and a longer treatment time in the high dependency unit . Despite a higher postoperative diuresis , no differences in the incidence of AKI grade 1 to 3 and the need for renal replacement were observed . Conclusions Routine perioperative administration of sodium bicarbonate failed to improve postoperative renal function in a large population of cardiac surgical patients " Recommendations for the management of crush victims in mass disasters " aims to assist medics , paramedics and rescue team members who provide care during disasters . Development of the recommendations followed an explicit process of literature review and , also internet and face-to-face discussion s. The chapters cover medical and logistic measures , to be taken both at the disaster field and in the hospitals , to cope with the problems created by a catastrophe . Recommendations were based on retrospective analyses and case reports on past disasters , and also expert judgment or opinion . Since there are no r and omized controlled trials , no GRADE approach was used to develop the recommendations , and no strengths of recommendations or levels of evidence are provided CONTEXT Contrast-induced nephropathy remains a common complication of radiographic procedures . Pretreatment with sodium bicarbonate is more protective than sodium chloride in animal models of acute ischemic renal failure . Acute renal failure from both ischemia and contrast are postulated to occur from free-radical injury . However , no studies in humans or animals have evaluated the efficacy of sodium bicarbonate for prophylaxis against contrast-induced nephropathy . OBJECTIVE To examine the efficacy of sodium bicarbonate compared with sodium chloride for preventive hydration before and after radiographic contrast . DESIGN , SETTING , AND PATIENTS A prospect i ve , single-center , r and omized trial conducted from September 16 , 2002 , to June 17 , 2003 , of 119 patients with stable serum creatinine levels of at least 1.1 mg/dL ( > or = 97.2 micromol/L ) who were r and omized to receive a 154-mEq/L infusion of either sodium chloride ( n = 59 ) or sodium bicarbonate ( n = 60 ) before and after iopamidol administration ( 370 mg iodine/mL ) . Serum creatinine levels were measured at baseline and 1 and 2 days after contrast . INTERVENTIONS Patients received 154 mEq/L of either sodium chloride or sodium bicarbonate , as a bolus of 3 mL/kg per hour for 1 hour before iopamidol contrast , followed by an infusion of 1 mL/kg per hour for 6 hours after the procedure . MAIN OUTCOME MEASURE Contrast-induced nephropathy , defined as an increase of 25 % or more in serum creatinine within 2 days of contrast . RESULTS There were no significant group differences in age , sex , incidence of diabetes mellitus , ethnicity , or contrast volume . Baseline serum creatinine was slightly higher but not statistically different in patients receiving sodium bicarbonate treatment ( mean [ SD ] , 1.71 [ 0.42 ] mg/dL [ 151.2 [ 37.1 ] micromol/L ] for sodium chloride and 1.89 [ 0.69 ] mg/dL [ 167.1 [ 61.0 ] micromol/L ] for sodium bicarbonate ; P = .09 ) . The primary end point of contrast-induced nephropathy occurred in 8 patients ( 13.6 % ) infused with sodium chloride but in only 1 ( 1.7 % ) of those receiving sodium bicarbonate ( mean difference , 11.9 % ; 95 % confidence interval [ CI ] , 2.6%-21.2 % ; P = .02 ) . A follow-up registry of 191 consecutive patients receiving prophylactic sodium bicarbonate and meeting the same inclusion criteria as the study result ed in 3 cases of contrast-induced nephropathy ( 1.6 % ; 95 % CI , 0%-3.4 % ) . CONCLUSION Hydration with sodium bicarbonate before contrast exposure is more effective than hydration with sodium chloride for prophylaxis of contrast-induced renal failure In a double-blinded r and omized controlled trial , Anja Haase-Fielitz and colleagues find that an infusion of sodium bicarbonate during open heart surgery did not reduce the risk for acute kidney injury , compared with saline control Background Acute kidney injury ( AKI ) requiring renal replacement therapy ( RRT ) is associated with high in-hospital morbidity and mortality in critically ill patients . Long-term outcomes have received little attention . Methods The aim of this study was to characterize AKI – chronic kidney disease ( CKD ) nexus in critically ill patients with AKI ( RIFLE class F ) . We performed a single-centre prospect i ve observational study of 425 consecutive critically ill patients with AKI requiring RRT . None of these patients had pre-existing kidney disease . Primary outcomes were vital status and renal function at hospital discharge and at 5 and 10 years of follow-up . Results The overall in-hospital mortality of the study cohort was 47 % , the mortality rates at 1 , 5 and 10 years were 65 , 75 and 80 % , respectively . At hospital discharge , recovery of renal function was complete in 56 % of survivors . None of these patients developed CKD during follow-up . Ninety percent of the 100 survivors with partial recovery of renal function had ongoing CKD during long-term follow-up . CKD progressed to end-stage renal disease ( ESRD ) in 12 patients ( 3 % of the cohort or 5 % of survivors ) . The patients with post-AKICKD had a higher prevalence of hypertension , a higher rate of fatal cardiac diseases and a higher all-cause death rate . Conclusion Long-term survival of critically ill patients with AKI requiring RRT is poor and determined by the development of de novo CKD . There is a need for close follow-up of patients surviving AKI to prevent progressive CKD and to reduce associated lethal cardiac events Iodine and gadolinium-based contrast induced nephropathy is the third leading cause of hospital-acquired acute kidney injury . It is essentially observed in patients with defined risk factors and is associated with increased morbidity and mortality . The prevention of contrast induced nephropathy consists in volume expansion through intravenous sodium chloride 0.9 % or sodium bicarbonate 1.4 % . Comparative r and omized controlled trials appear to show a benefit in favor of sodium bicarbonate over saline fluids . According to last evidence , N-acetylcysteine does not provide additional benefit over intravenous fluids BACKGROUND There is controversy about the prophylactic measures proposed for the prevention of contrast-induced nephropathy ( CIN ) . We aim to compare the efficacy of the combination of sodium bicarbonate and isotonic saline and that of isotonic saline alone in preventing CIN . STUDY DESIGN R and omized double-blind controlled trial . SETTING & PARTICIPANTS 265 consecutive patients 18 years or older with a serum creatinine level of 1.5 mg/dL or greater undergoing elective coronary angiography from August 2007 to June 2008 in Tehran Heart Center , Tehran , Iran . INTERVENTION Study participants were r and omly assigned to receive either 75 mL of 8.4 % sodium bicarbonate added to 1 L of isotonic saline ( n = 135 ) or isotonic saline alone ( n = 130 ) as a bolus of 3 mL/kg for 1 hour before contrast injection , followed by an infusion of 1 mL/kg/h for 6 hours after the procedure . OUTCOMES & MEASUREMENTS The primary end point was an absolute ( > or=0.5 mg/dL ) or relative ( > or=25 % ) increase in serum creatinine level 48 hours after the procedure ( CIN ) . RESULTS There were no significant differences between the bicarbonate and saline groups regarding baseline demographic and biochemical characteristics , including baseline serum creatinine level ( 1.63 + /- 0.32 [ SD ] versus 1.66 + /- 0.50 mg/dL ) , baseline glomerular filtration rate ( 46.4 + /- 12 versus 45.4 + /- 12 mL/min/1.73 m(2 ) ) , and baseline urine pH ( 5.42 + /- 0.6 versus 5.46 + /- 0.8 ) . Nine patients ( 7.4 % ) receiving sodium bicarbonate developed CIN as opposed to 7 patients ( 5.9 % ) in the saline group , which was not statistically different ( odds ratio , 1.26 ; 95 % confidence interval , 0.45 to 3.50 ; P = 0.6 ) . LIMITATIONS The trial did not follow up participants to assess need for dialysis and mortality rate . CONCLUSION The combination therapy of sodium bicarbonate plus saline does not offer additional benefits over hydration with saline alone in the prevention of CIN Objectives : Cardiac surgery – associated acute kidney injury occurs in up to 50 % of patients and is associated with increased mortality and morbidity . This study aim ed to discover if perioperative urinary alkalinization with sodium bicarbonate infusion reduces the prevalence of cardiac surgery – associated acute kidney injury . Design : This study was a phase IIb multicenter double-blind r and omized controlled trial . Setting : This study was conducted in three tertiary hospitals in New Zeal and and Australia . Patients : A total of 427 patients scheduled to undergo elective cardiac surgery , who were at increased risk of development of cardiac surgery – associated acute kidney injury using recognized risk factors . Measurements and Main Results : Patients were r and omly allocated to receive either sodium bicarbonate ( n = 215 ) or sodium chloride ( n = 212 ) infusion , commencing at the start of anesthesia , in a dose of 0.5 mEq/kg/hr for the first hour and then 0.2 mmol/kg/hr for 23 hours . The primary outcome measure was the number of patients with development of cardiac surgery – associated acute kidney injury , defined as an increase in creatinine greater than 25 % or 0.5 mg/dL ( 44 µmol/L ) from baseline to peak value within the first five postoperative days . Significant differences among the groups in both plasma and urinary biochemistry were achieved 6 hours after commencement of the infusion , and these changes persisted for more than 24 hours . A total of 100 out of 215 patients ( 47 % [ 95 % CI , 40%–53 % ] ) in the sodium bicarbonate group and 93 of 212 patients ( 44 % [ 95 % CI , 37%–51 % ] ) in the sodium chloride group with development of acute kidney injury within the first five postoperative days ( p = 0.58 ) . There were also no significant differences in ventilation hours , ICU or hospital length of stay , or mortality . Conclusions : Perioperative alkalinization of blood and urine using an infusion of sodium bicarbonate did not result in a decrease in the prevalence of acute kidney injury in patients following cardiac surgery BACKGROUND The contrast-induced nephropathy ( CIN ) is the third most common cause of acute renal failure ( ARF ) and the worsening in a pre-existing chronic renal failure ( CRF ) , with a foreseeable increase of morbidity , mortality , length of the stay in hospital and , as a consequence , of the health costs . We studied the effectiveness of N-acetylcysteine ( NAC ) associated with sodium bicarbonate ( Na2HCO3 ) infusion in order to prevent CIN in patients undergoing coronary angiography with administration of contrast medium . MATERIAL S AND METHODS 296 patients with indication to perform coronary angiography were included in a r and omized , observational study . All patients were r and omly assigned to receive pre- and post-contrast hydration with 1500 ml of 0.9 % saline solution infusion ( Group A ) or NAC ( 1200 mg × 2 days ) + Na2HCO3 ( Group B ) . The primary end-point was to examine CIN appearance , defined as a raise in serum values of Cr ( Creatinine ) ≥ 0.5 mg/dl or ≥ 25 % within 24 - 72 hours after the exposure to the contrast medium . RESULTS It has been observed a frequency of CIN of 9.4 % in Gr . A compared to 7.2 % in Gr . B. Nevertheless , when we put these results through a more accurate screening according to gender , degree of raise in creatinine levels and the extent of change in GFR ( glomerular filtration rate ) , we observed a very different behaviour . In patients with normal Cr and CrCl ( Clearance of Creatinine ) the frequency of CIN was similar in both group A and B ( approximately 5 % ) . In patients with normal Cr but reduced ClCr the use of NAC was more effective than hydration in preventing CIN ( 0 % vs 18 % in prevalence respectively in B and A group ) . In patients with moderately reduced Cr and CrCl , hydration with saline solution was more effective than NAC + Na2HCO3 ( 8.6 % vs 17.6 % ) while in patients with severe CRF the combined use of NAC + Na2HCO3 showed off to be very successful in preventing CIN compared to the merely hydration ( 0 % vs 50 % ) . CONCLUSIONS In patients affected by severe CRF who are undergoing investigations with contrast medium administration , such as coronary angiography , the combined use of NAC + Na2HCO3 infusion significantly reduces the risk of developing CIN . In other circumstances the final result is related to the degree of previous GFR or creatinine values alteration or to gender . In such situations the combined use of both substances is more question able and sometimes ineffective BACKGROUND Sodium bicarbonate has been recently proposed as a prophylactic measure for the prevention of contrast-induced nephropathy ( CIN ) . We aim ed to compare the efficacy of the combination of sodium bicarbonate with half saline , and half saline alone in preventing CIN in patients having uncontrolled hypertension , compensated severe heart failure or a history of pulmonary edema . METHODS Seventy-two patients undergoing elective coronary angiography with a serum creatinine level > or = 1.5 mg/dL who had uncontrolled hypertension , compensated severe heart failure or a history of pulmonary edema were prospect ively enrolled in a single-center , double-blind , r and omized , controlled trial from August 2007 to July 2008 and were assigned to either an infusion of sodium bicarbonate plus half saline ( n=36 ) or half saline alone ( n=36 ) . The primary end point was an absolute ( > or = 0.5 mg/dL ) or relative ( > or = 25 % ) increase in serum creatinine 48 hours after the procedure ( CIN ) . RESULTS There were no significant differences between the groups regarding their baseline demographic and biochemical characteristics , as well as the underlying disease . A total of 6.1 % of the patients receiving sodium bicarbonate plus half saline developed CIN as opposed to 6.3 % of the patients in the half saline group , which was not statistically different ( odds ratio = 0.97 ; 95 % confidence interval , 0.13 - 7.3 ; p=1.0 ) . CONCLUSION The combination therapy of sodium bicarbonate plus half saline does not offer additional benefits over hydration with half saline alone in the prevention of CIN Objective : We compared use of intravenous ( IV ) normal saline ( NS ) to sodium bicarbonate ( NaHCO3 ) with or without oral N‐acetylcysteine ( NAC ) for prevention of contrast‐induced acute kidney injury ( CI‐AKI ) . Background : CI‐AKI is associated with significant adverse clinical events . Use of NAC has produced variable results . Recently , intravenous hydration with NaHCO3 for CI‐AKI prophylaxis has been adopted as st and ard treatment for patients with stable chronic renal disease undergoing catheterization procedures . Methods : We prospect ively enrolled 320 patients with baseline renal insufficiency scheduled to undergo catheterization . Patients were r and omly assigned to receive either IV NS ± NAC ( n = 161 ) or IV dextrose 5 % in water containing 154 mEq/l of NaHCO3 ± NAC ( n = 159 ) . IV NS was administered at 1 ml/kg body weight for 12 hr preprocedure and 12 more hr postprocedure . IV NaHCO3 was administered at 3 ml/kg body weight for 1 hr preprocedure followed by 1 ml/kg body weight postprocedure . A 1,200 mg oral dose of NAC was given 2–12 hr preprocedure and 6–12 hr postprocedure in 50 % of patients in each study arm . CI‐AKI was defined as an increase of > 0.5 mg/dl or > 25 % above baseline creatinine . Results : Overall incidence of CI‐AKI was 10.3 % . There was no significant difference in incidence among the two groups ( NS ± NAC 11.8 % vs. NaHCO3 ± NAC 8.8 % , p = ns ) . Incidence of CI‐AKI increased with increasing age ( p = 0.001 ) , contrast agent use > 3 ml/kg body weight ( p = 0.038 ) and diuretic use ( p = 0.005 ) . Conclusion : Incidence of CI‐AKI was no different in the NaHCO3 group compared to NS group , and NAC did not reduce CI‐AKI in the two study arms . © 2011 Wiley Periodicals , INTRODUCTION Contrast-induced acute kidney injury ( CI-AKI ) is one of the leading causes of hospital-acquired acute kidney injury . Multiple clinical studies have proposed several preventive strategies . AIMS To examine the efficacy of sodium bicarbonate compared with sodium chloride and oral N-acetylcysteine ( NAC ) for preventive hydration after cardiac catheterization . METHODS We conducted a prospect i ve , single-center trial . Patients with chronic kidney disease ( CKD ) stage III-IV undergoing cardiac catheterization were allocated to receive either an infusion of 0.9 % sodium chloride and oral NAC or 154 mEq/L sodium bicarbonate . MAIN : Outcome measure CI-AKI , defined as an increase of 25 % or 0.3 mg/dL or more in plasma creatinine within 2 days of contrast administration . RESULTS Ninety-three patients were allocated to one of the two groups : 42 patients in the saline plus NAC group and 51 patients in the bicarbonate group . There were no statistically significant differences between the groups in the most important clinical and procedural characteristics . Baseline plasma creatinine levels , estimated glomerular filtration rate , incidence of diabetes mellitus , hypertension , congestive heart failure , and contrast medium volume were similar . Mean plasma creatinine concentration was 1.76 + /- 0.54 mg/dL in the saline and NAC group and 1.9 + /- 1 mg/dL in the bicarbonate group ( P = 0.23 ) . The rate of CI-AKI was 9.8 % in the bicarbonate group and 8.4 % in the saline plus NAC group . No patient required renal replacement therapy . CONCLUSION Hydration with sodium bicarbonate is not more effective than hydration with sodium chloride and oral NAC for prophylaxis of CI-AKI in patients with CKD stage III-IV undergoing cardiac catheterization AIMS Diabetes mellitus and decreased renal function are important risk factors for contrast-induced nephropathy ( CIN ) in which oxidative stress damage may play a role . Alkalinization with sodium bicarbonate ( NaHCO₃ ) has been proposed as a means of reducing free-radical mediated renal injury ; however , the effectiveness of NaHCO₃ treatment to prevent CIN in high-risk patients remains uncertain . METHODS We performed a prospect i ve , r and omized , double blind , sodium chloride ( NaCl ) hydration-controlled study of NaHCO₃ in 120 diabetic patients with impaired renal function ( serum creatinine ≥100 μmol/L ) undergoing an elective procedure with use of low-osmolar contrast media . The primary endpoint was the incidence of CIN defined as creatinine increase of ≥25 % and /or ≥44 μmol/L within 2 days after contrast . Secondary end-points were maximal changes in serum creatinine and estimated glomerular filtration rate . Urine F₂-isoprostane levels were also assessed as measure of oxidative stress . RESULTS There were no significant group differences in baseline characteristics except for the marginally lower age of the NaHCO₃ treated patients ( 63 ± 11 vs. 67 ± 10 years ; p=0.05 ) . CIN occurred in 7 ( 11.5 % ) and 5 ( 8.5 % ) patients of the NaHCO₃ and NaCl groups , respectively ( p=0.76 ; incidence rate ratio 1.35 ; 95 % CI 0.37 - 5.41 ) . No significant differences were seen in secondary outcome measures and changes in the parameter of oxidative stress . CONCLUSIONS In diabetic patients with renal function impairment sodium bicarbonate does not confer protection against contrast-induced nephropathy greater than sodium chloride-based hydration . Its specific role in mitigating oxidative stress damage in CIN is also not supported by our data Background Contrast-induced nephropathy ( CIN ) is commonly encountered . Because the therapy of choice for prevention of CIN is controversial , in this study we compared the preventive efficacy of bicarbonate ( Bi ) infusion in dextrose water versus normal saline ( NLS ) infusion alone or in combination with oral acetazolamide ( AZ ) . Methods In a double-blind and r and omized clinical trial , all patients undergoing coronary angiography or percutaneous coronary intervention received NLS ( NLS group ) , its combination with AZ ( AZ group ) or infusion of Bi ( Bi group ) before the procedures . RIFLE ( risk of renal failure , injury to the kidney , failure of kidney function , loss of kidney function , and end-stage renal disease ) criteria were used to define CIN-associated acute kidney injury ( AKI ) . Results The risk of AKI in CIN was significantly lower in the Bi and AZ groups than in the NLS group ( P ≤ 0.04 ) . Comparing pre-treatment and post-treatment values in each group the following results were obtained : serum creatinine ( Scr ) increased and eGFR decreased significantly in the NLS group ( P = 0.04 ) and in all patients ( P = 0.001 , P = 0.02 , respectively ) . In addition , serum potassium decreased significantly in the Bi and NLS groups ( P ≤ 0.02 ) . Also , serum Bi increased significantly in the Bi group ( P = 0.001 ) whereas it decreased significantly in the AZ group ( P = 0.001 ) . Urinary pH also increased in all groups ( P ≤ 0.04 ) except the NLS group ( P > 0.05 ) . Conclusions It seems that both Bi and AZ reduce the risk of CIN-related AKI , and close monitoring of serum potassium is needed during bicarbonate infusion BACKGROUND Urine alkalinisation with sodium bicarbonate decreases renal oxidative stress and might attenuate sepsisassociated acute kidney injury ( s-AKI ) . The safety and feasibility of urine alkalinisation in patients at risk of s-AKI has never been tested . METHODS We r and omly assigned patients at risk of s-AKI ( those with systemic inflammatory response syndrome [ SIRS ] , oliguria and elevated [ ≥150 µg/L ] serum neutrophil gelatinase-associated lipocalin [ sNGAL ] concentration ) to receive sodium bicarbonate ( treatment group ) or sodium chloride ( placebo group ) in a 0.5 mmol/kg bolus followed by an infusion of 0.2 mmol/kg/hour . RESULTS Among 50 patients with SIRS and oliguria , 25 ( 50 % ) had an elevated sNGAL concentration . Of these , 13 were r and omised to receive sodium bicarbonate and 12 to receive sodium chloride infusion . Study drugs were infused for a mean period of 25.9 hours ( SD , 10 hours ) . Severe electrolyte abnormalities occurred in seven patients ( 28 % ) ( four [ 30.8 % ] in the treatment group and three [ 25 % ] in the placebo group ) . These abnormalities result ed in early protocol cessation in six patients ( 24 % ) and study drug suspension in one patient ( 4 % ) . This adverse event rate was judged to be unacceptable and the study was terminated early . There was no difference between the two groups in sNGAL or urinary NGAL concentrations over time , occurrence of acute kidney injury , requirement for renal replacement therapy , hospital length-of-stay or mortality . CONCLUSION Administration of sodium bicarbonate and sodium chloride solutions to patients at risk of s-AKI was associated with frequent major electrolyte abnormalities and early protocol cessation . The tested protocol does not appear safe or feasible BACKGROUND Radiographic contrast media exposition can cause acute renal function impairment . There is limited and conflicting evidence that hydration with sodium bicarbonate prevents contrast-induced nephropathy ( CIN ) in patients undergoing cardiac catheterization . OBJECTIVE The present study was aim ed at determining whether sodium bicarbonate is superior to hydration with saline to prevent nephropathy in patients at risk undergoing cardiac catheterization . METHODS Three hundred and one patients undergoing coronary angiography or percutaneous coronary intervention with serum creatinine > 1.2mg/dL or glomerular filtration rate ( GFR ) < 50 ml/min were r and omized to receive hydration with sodium bicarbonate starting 1 hour before the procedure and 6 hours after the procedure , or hydration with 0.9 % saline . CIN was defined as an increase of 0.5mg/dL in creatinine in 48 h RESULTS Eighteen patients ( 5.9 % ) developed contrast induced nephropathy : 9 patients in the bicarbonate group ( 6.1 % ) and 9 patients in the saline group ( 6.0 % ) , p = 0.97 . The change in serum creatinine was similar in both groups , 0.01 ± 0.26 mg/dL in the bicarbonate group and 0.01 ± 0.35 mg/dL in the saline group , p = 0.9 . No statistical difference was observed between the change in glomerular filtration rate ( 0.89 ± 9 ml/min vs. 2.29 ± 10 ml/min , p = 0.2 bicarbonate group and saline group , respectively ) . CONCLUSION Hydration with sodium bicarbonate was not superior to saline to prevent contrast media induced nephropathy in patients at risk undergoing cardiac catheterization Objective : To test whether perioperative sodium bicarbonate infusion can attenuate postoperative increases in serum creatinine in cardiac surgical patients . Design : Double-blind , r and omized controlled trial . Setting : Operating rooms and intensive care unit at a tertiary hospital . Patients : Cohort of 100 cardiac surgical patients at increased risk of postoperative acute renal dysfunction . Intervention : Patients were r and omized to either 24 hrs of intravenous infusion of sodium bicarbonate ( 4 mmol/kg ) or sodium chloride ( 4 mmol/kg ) . Measurements and Main Results : The primary outcome measure was the proportion of patients developing acute renal dysfunction defined as a postoperative increase in plasma creatinine concentration > 25 % of baseline within the first five postoperative days . Secondary outcomes included changes in plasma creatinine , plasma urea , urinary neutrophil gelatinase-associated lipocalin , and urinary neutrophil gelatinase-associated lipocalin/urinary creatinine ratio . Patients were well balanced for baseline characteristics . Sodium bicarbonate infusion increased plasma bicarbonate concentration ( p < 0.001 ) , base excess ( p < 0.001 ) , plasma pH ( p < 0.001 ) , and urine pH ( p < 0.001 ) . Fewer patients in the sodium bicarbonate group ( 16 of 50 ) developed a postoperative increase in serum creatinine compared with control ( 26 of 50 ) ( odds ratio 0.43 [ 95 % confidence interval 0.19–0.98 ] ) , ( p = 0.043 ) . The increase in plasma creatinine , plasma urea , urinary neutrophil gelatinase-associated lipocalin , and urinary neutrophil gelatinase-associated lipocalin/urinary creatinine ratio was less in patients receiving sodium bicarbonate , ( p = 0.014 ; p = 0.047 ; p = 0.009 ; p = 0.004 ) . There were no significant side effects . Conclusions : Sodium bicarbonate loading and continuous infusion was associated with a lower incidence of acute renal dysfunction in cardiac surgical patients undergoing cardiopulmonary bypass . The findings of this pilot study justify further investigation . ( Clinical Trials.gov , NCT00334191 ) Introduction Contrast-induced nephropathy ( CIN ) is a leading cause of acute renal failure and affects mortality and morbidity . Although the incidence of CIN is quite low in the general population , CIN incidence is significantly increased in patients with diabetes mellitus ( DM ) . Objectives We compared the efficacy of prophylactic use consisting of a saline infusion or a sodium bicarbonate infusion for the prevention of CIN in patients with DM . Material s and Methods A total of 195 DM patients who had unselected renal function were r and omized into 2 groups : 101 patients were assigned to saline infusion , and 94 patients were assigned to bicarbonate infusion . The primary end point was the maximum increase in the serum creatinine ( SCr ) level , whereas the secondary end point was the development of CIN after the procedure . Results The maximum increase in SCr levels was significantly lower in the saline group than in the bicarbonate group : −0.03 mg/dL ( IQR , −0.09 to 0.10 mg/dL ) versus 0.02 mg/dL ( IQR , −0.09 to 0.13 mg/dL ) ( P = 0.014 ) . The rate of CIN was significantly lower in the saline group than in the bicarbonate group ( 5.9 % vs 16 % , P = 0.024 ) . In the subset of study participants with a baseline creatinine clearance of less than 60 mL/min , the maximum increase in SCr levels was significantly lower , −0.08 mg/dL ( IQR , −0.13 to −0.04 mg/dL ) , in the saline group than in the bicarbonate group , 0.03 mg/dL ( IQR , −0.13 to 0.12 mg/dL ) ( P = 0.004 ) . Conclusions The use of prophylactic hydration with isotonic saline before coronary procedures may decrease SCr levels and reduce the incidence of CIN in patients with DM with unselected renal functions to a greater extent than sodium bicarbonate can |
1,227 | 28,653,751 | VSL#3 may be effective in inducing remission in active UC .
Probiotics may be as effective as 5-ASAs in preventing relapse of quiescent UC . | BACKGROUND Ulcerative colitis ( UC ) and Crohn 's disease ( CD ) are inflammatory bowel diseases ( IBD ) .
Evidence implicates disturbances of the gastrointestinal microbiota in their pathogenesis .
AIM To perform a systematic review and meta- analysis to examine the efficacy of probiotics in IBD . | Eighty-nine patients who had been treated by ileal resection for Crohn 's disease between 1979 and 1984 were included in a prospect i ve cohort follow up to study the natural course of early postoperative lesions . Recurrent lesions were observed endoscopically in the neoterminal ileum within 1 year of surgery in 73 % of the patients , although only 20 % of the patients had symptoms . Three years after surgery , the endoscopic recurrence rate had increased to 85 % and symptomatic recurrence occurred in 34 % . The ultimate course of the disease was best predicted by the severity of the early postoperative lesions , as observed at ileoscopy . Clinical parameters that influenced outcome were preoperative disease activity , the indication for surgery , and the number of surgical resections . When patients were stratified for preoperative disease activity , the severity of lesions found at endoscopy remained a strong predictive factor for symptomatic recurrence . In 22 other patients su bmi tted to " curative " ileal resection and ileocolonic anastomosis , the segment to be used as neoterminal ileum was carefully examined during surgery , and two large biopsies were taken before making the anastomosis . An ileoscopy was performed 6 months after surgery . Although all patients had a macroscopically normal neoterminal ileum and 19 had entirely normal biopsies at the time of surgery , 21 patients were found at ileoscopy to have developed ileitis involving a 15-cm segment ( range , 4 - 30 cm ) , and 20 had unequivocal microscopic lesions on biopsies . These studies suggest that early lesions in the neoterminal ileum after Crohn 's resection do not originate from microscopic inflammation present in this bowel segment at the time of surgery . The early postoperative lesions in the neoterminal ileum seem to be a suitable model to study the pathogenesis of Crohn 's disease and also to evaluate new therapeutic modalities , either to prevent development of these early lesions or to treat progressive recurrence Background : Probiotics are efficacious for treating and maintaining remission of ulcerative colitis OBJECTIVES : VSL#3 is a high-potency probiotic mixture that has been used successfully in the treatment of pouchitis . The primary end point of the study was to assess the effects of supplementation with VSL#3 in patients affected by relapsing ulcerative colitis ( UC ) who are already under treatment with 5-aminosalicylic acid ( ASA ) and /or immunosuppressants at stable doses . METHODS : A total of 144 consecutive patients were r and omly treated for 8 weeks with VSL#3 at a dose of 3,600 billion CFU/day ( 71 patients ) or with placebo ( 73 patients ) . RESULTS : In all , 65 patients in the VSL#3 group and 66 patients in the placebo group completed the study . The decrease in ulcerative colitis disease activity index ( UCDAI ) scores of 50 % or more was higher in the VSL#3 group than in the placebo group ( 63.1 vs. 40.8 ; per protocol ( PP ) P=0.010 , confidence interval (CI)95 % 0.51–0.74 ; intention to treat ( ITT ) P=0.031 , CI95 % 0.47–0.69 ) . Significant results with VSL#3 were recorded in an improvement of three points or more in the UCDAI score ( 60.5 % vs. 41.4 % ; PP P=0.017 , CI95 % 0.51–0.74 ; ITT P=0.046 , CI95 % 0.47–0.69 ) and in rectal bleeding ( PP P=0.014 , CI95 % 0.46–0.70 ; ITT P=0.036 , CI95 % 0.41–0.65 ) , whereas stool frequency ( PP P=0.202 , CI95 % 0.39–0.63 ; ITT P=0.229 , CI95 % 0.35–0.57 ) , physician 's rate of disease activity ( PP P=0.088 , CI95 % 0.34–0.58 ; ITT P=0.168 , CI95 % 0.31–0.53 ) , and endoscopic scores ( PP P=0.086 , CI95 % 0.74–0.92 ; ITT P=0.366 , CI95 % 0.66–0.86 ) did not show statistical differences . Remission was higher in the VSL#3 group than in the placebo group ( 47.7 % vs. 32.4 % ; PP P=0.069 , CI95 % 0.36–0.60 ; ITT P=0.132 , CI95 % 0.33–0.56 ) . Eight patients on VSL#3 ( 11.2 % ) and nine patients on placebo ( 12.3 % ) reported mild side effects . CONCLUSIONS : VSL#3 supplementation is safe and able to reduce UCDAI scores in patients affected by relapsing mild-to-moderate UC who are under treatment with 5-ASA and /or immunosuppressants . Moreover , VSL#3 improves rectal bleeding and seems to reinduce remission in relapsing UC patients after 8 weeks of treatment , although these parameters do not reach statistical significance BACKGROUND & AIMS Saccharomyces boulardii is a probiotic yeast that has been shown to have beneficial effects on the intestinal epithelial barrier and digestive immune system . There is preliminary evidence that S boulardii could be used to treat patients with Crohn 's disease ( CD ) . We performed a r and omized , placebo-controlled trial to evaluate the effects of S boulardii in patients with CD who underwent remission during therapy with steroids or aminosalicylates . METHODS We performed a prospect i ve study of 165 patients who achieved remission after treatment with steroids or salicylates ; they were r and omly assigned to groups given S boulardii ( 1 g/day ) or placebo for 52 weeks . The primary end point was the percentage of patients in remission at week 52 . Time to relapse , Crohn 's disease activity index scores , and changes in parameters of inflammation were secondary end points . RESULTS CD relapsed in 80 patients , 38 in the S boulardii group ( 47.5 % ) and 42 in the placebo group ( 53.2 % , a nonsignificant difference ) . The median time to relapse did not differ significantly between patients given S boulardii ( 40.7 weeks ) vs placebo ( 39.0 weeks ) . There were no significant differences between groups in mean Crohn 's disease activity index scores or erythrocyte sedimentation rates or in median levels of C-reactive protein . In a post hoc analysis , nonsmokers given S boulardii were less likely to experience a relapse of CD than nonsmokers given placebo , but this finding requires confirmation . CONCLUSIONS Although the probiotic yeast S boulardii is safe and well tolerated , it does not appear to have any beneficial effects for patients with CD in remission after steroid or salicylate therapies AIM To investigate the effects of probiotic on intestinal mucosae of patients with ulcerative colitis ( UC ) , and to evaluate the role of probiotic in preventing the relapse of UC . METHODS Thirty patients received treatment with sulphasalazine ( SASP ) and glucocorticoid and then were r and omly administered bifid triple viable capsule ( BIFICO ) ( 1.26 g/d ) , or an identical placebo ( starch ) for 8 wk . Fecal sample s were collected for stool culture 2 wk before and after the r and omized treatments . The patients were evaluated clinical ly , endoscopically and histologically after 2 mo of treatment or in case of relapse of UC . p65 and IkappaB expressions were determined by Western blot analysis . DNA-binding activity of NF-kappaB in colonic nuclear extracts was detected by electrophoretic mobility shift assay ( EMSA ) . mRNA expressions of cytokines were identified by semi-quantitative assay , reverse transcriptase- polymerase chain reaction ( RT-PCR ) . RESULTS Three patients ( 20 % ) in the BIFICO group had relapses during 2-mo follow-up period , compared with 14 ( 93.3 % ) in placebo group ( P<0.01 ) . The concentration of fecal lactobacilli , bifidobacteria was significantly increased in BIFICO-treated group only ( P<0.01 ) . The expressions of NF-kappaB p65 and DNA binding activity of NF-kappaB were significantly attenuated in the treatment group than that in control ( P<0.05 ) . The mRNA expression of anti-inflammatory cytokines was elevated in comparison with the control group . CONCLUSION The probiotic could impede the activation of NF-kappaB , decrease the expressions of TNF-alpha and IL-1beta and elevate the expression of IL-10 . These results suggest that oral administration of this new probiotic preparation is effective in preventing flare-ups of chronic UC . It may become a prophylactic drug to decrease the relapse of UC Background and aims : Experimental studies have shown that luminal bacteria may be involved in Crohn 's disease . Probiotics are a possible alternative to antibiotics . The aim of this r and omised placebo controlled study was to determine if Lactobacillus GG , given by mouth for one year , could prevent Crohn 's recurrent lesions after surgery or to reduce their severity . Methods : Patients operated on for Crohn 's disease in whom all of the diseased gut had been removed were r and omly allocated to receive 12 billion colony forming units of Lactobacillus or identical placebo for one year . Ileocolonoscopy was performed at the end of the trial or at the onset of symptoms . Endoscopic recurrence was defined as grade 2 or higher of Rutgeerts scoring system . Results : Eight of 45 patients were excluded from the trial ( three for non-compliance and five for protocol violations ) . Clinical recurrence was ascertained in three ( 16.6 % ) patients who received Lactobacillus and in two ( 10.5 % ) who received placebo . Nine of 15 patients in clinical remission on Lactobacillus ( 60 % ) had endoscopic recurrence compared with six of 17 ( 35.3 % ) on placebo ( p=0.297 ) . There were no significant differences in the severity of the lesions between the two groups . Conclusions : Lactobacillus GG seems neither to prevent endoscopic recurrence at one year nor reduce the severity of recurrent lesions Background Experimental studies have shown that luminal antigens are involved in chronic intestinal inflammatory disorders such as Crohn 's disease and ulcerative colitis . Alteration of the intestinal microflora by antibiotic or probiotic therapy may induce and maintain remission . The aim of this r and omized , placebo-controlled trial was to determine the effect of oral Lactobacillus GG ( L. GG ) to induce or maintain medically induced remission . Methods Eleven patients with moderate to active Crohn 's disease were enrolled in this trial to receive either L. GG ( 2 × 109 CFU/day ) or placebo for six months . All patients were started on a tapering steroid regime and received antibiotics for the week before the probiotic/placebo medication was initiated . The primary end point was sustained remission , defined as freedom from relapse at the 6 months follow-up visit . Relapse was defined as an increase in CDAI of > 100 points . Results 5/11 patients finished the study , with 2 patients in each group in sustained remission . The median time to relapse was 16 ± 4 weeks in the L. GG group and 12 ± 4.3 weeks in the placebo group ( p = 0.5 ) . Conclusion In this study we could not demonstrate a benefit of L. GG in inducing or maintaining medically induced remission in CD Guidelines for clinical practice are intended to suggest preferable approaches to particular medical problems as established by interpretation and collation of scientifically valid research , derived from extensive review of published literature . When data that will withst and objective scrutiny are not available , a recommendation may be made based on a consensus of experts . Guidelines are intended to apply to the clinical situation for all physicians without regard to specialty . Guidelines are intended to be flexible , not necessarily indicating the only acceptable approach , and should be distinguished from st and ards of care that are inflexible and rarely violated . Given the wide range of choices in any health-care problem , the physician should select the course best suited to the individual patient and the clinical situation presented . These guidelines are developed under the auspices of the American College of Gastroenterology and its Practice Parameters Committee . Expert opinion is solicited from the outset for the document . The quality of evidence upon which a specific recommendation is based is as follows : Grade A : Homogeneous evidence from multiple well- design ed r and omized ( therapeutic ) or cohort ( descriptive ) controlled trials , each involving a number of participants to be of sufficient statistical power . Grade B : Evidence from at least one large well- design ed clinical trial with or without r and omization , from cohort or case – control analytic studies , or well- design ed meta- analysis . Grade C : Evidence based on clinical experience , descriptive studies , or reports of expert committees . The Committee review s guidelines in depth , with participation from experienced clinicians and others in related fields . The final recommendations are based on the data available at the time of the production of the document and may be up date d with pertinent scientific developments at a later time BACKGROUND AND AIM Ulcerative colitis ( UC ) is a chronic inflammatory bowel disease . The probiotic bacterium Escherichia coli Nissle 1917 ( EcN ) has been used to maintain and induce clinical remission in UC . Our aim was to test the effect of Ciprofloxacin and /or orally administered EcN as add-on to conventional therapies in patients with active UC . PATIENTS AND METHODS Our single center double-blinded r and omized placebo controlled study included patients with a Colitis Activity Index ( CAI ) score of at least 6 . Patients were r and omized to Ciprofloxacin or placebo for 1week followed by EcN or placebo for 7weeks . All 4 treatments were given as add-on treatments . RESULTS One hundred subjects with active UC were recruited . In the per- protocol analysis we , surprisingly , found that in the group receiving placebo/EcN fewer patients , 54 % , reached remission compared to the group receiving placebo/placebo , 89 % , p<0.05 . Among patients treated with Cipro/placebo and Cipro/EcN , 78 % and 66 % reached remission , respectively . Furthermore , the group receiving placebo/EcN had the largest number of withdrawals , 11 of 25 ( 44 % ) , compared to 15 of 75 ( 20 % ) in any of the other groups , p<0.05 . Indication of lack of mucosal healing was found in the group treated with placebo/Nissle , since only 4 ( 29 % ) of the 14 patients , who completed the study , reported no blood in stools at week 12 ( p<0.02 ) , compared to 63 % , 67 % and 65 % in groups treated with Cipro/Nissle , Cipro/placebo and placebo/placebo , respectively . CONCLUSIONS Our data suggest that there is no benefit in the use of E. coli Nissle as an add-on treatment to conventional therapies for active ulcerative colitis . Furthermore , treatment with E. coli Nissle without a previous antibiotic cure result ed in fewer patients reaching clinical remission Background and aims : Early endoscopic recurrence is frequent after intestinal resection for Crohn ’s disease . Bacteria are involved , and probiotics may modulate immune responses to the intestinal flora . Here we tested the probiotic strain Lactobacillus johnsonii LA1 in this setting . Patients and methods : This was a r and omised , double blind , placebo controlled study . Patients were eligible if they had undergone surgical resection of < 1 m , removing all macroscopic lesions within the past 21 days . Patients were r and omised to receive two packets per day of lyophilised LA1 ( 2 × 109 cfu ) or placebo for six months ; no other treatment was allowed . The primary endpoint was endoscopic recurrence at six months , with grade > 1 in Rutgeerts ’ classification or an adapted classification for colonic lesions . Endoscopic score was the maximal grade of ileal and colonic lesions . Analyses were performed primarily on an intent to treat basis . Results : Ninety eight patients were enrolled ( 48 in the LA1 group ) . At six months , endoscopic recurrence was observed in 30/47 patients ( 64 % ) in the placebo group and in 21/43 ( 49 % ) in the LA1 group ( p = 0.15 ) . Per protocol analysis confirmed this result . Endoscopic score distribution did not differ significantly between the LA1 and placebo groups . There were four clinical recurrences in the LA1 group and three in the placebo group . Conclusion : L johnsonii LA1 ( 4 × 109 cfu/day ) did not have a sufficient effect , if any , to prevent endoscopic recurrence of Crohn ’s disease Background Probiotics are effective in inflammatory bowel diseases . Clinical effectiveness and dose dependency of E. coli Nissle ( EcN ) enemas were investigated in ulcerative colitis ( UC ) . Methods In a double-blind study , 90 patients with moderate distal activity in UC were r and omly assigned to treatment with either 40 , 20 , or 10 ml enemas ( N = 24 , 23 , 23 ) containing 10E8 EcN/ml or placebo ( N = 20 ) . The study medication was taken once daily for at least 2 weeks . After 2 , 4 and /or 8 weeks the clinical DAI was assessed together with tolerance to treatment . Patients who reached clinical DAI ≤ 2 within that time were regarded as responders . Results According to ITT analysis the number of responders was not significantly higher in the EcN group than in the placebo group ( p = 0.4430 , 2-sided ) . However , the Jonckheere-Terpstra rank correlation for dose-dependent efficacy indicated a significant correlation of per- protocol responder rates ( p = 0.0446 , 2-sided ) . Time to remission was shortest with EcN 40 ml , followed by EcN 20 ml . The number of adverse events did not differ notably . Conclusion In contrast to ITT analysis , efficacy of rectal EcN application was significant in PP and points to EcN as a well tolerated treatment alternative in moderate distal UC.Trial registration German Clinical Trials Register DRK00000234 Guidelines for clinical practice are aim ed to indicate preferred approaches to medical problems as established by scientifically valid research . Double-blind placebo controlled studies are preferable , but compassionate-use reports and expert review articles are used in a thorough review of the literature conducted through Medline with the National Library of Medicine . When only data that will not withst and objective scrutiny are available , a recommendation is identified as a consensus of experts . Guidelines are applicable to all physicians who address the subject regardless of specialty training or interests and are aim ed to indicate the preferable but not necessarily the only acceptable approach to a specific problem . Guidelines are intended to be flexible and must be distinguished from st and ards of care , which are inflexible and rarely violated . Given the wide range of specifics in any health-care problem , the physician must always choose the course best suited to the individual patient and the variables in existence at the moment of decision . Guidelines are developed under the auspices of the American College of Gastroenterology and its Practice Parameters Committee and approved by the board of trustees . Each has been intensely review ed and revised by the Committee , other experts in the field , physicians who will use them , and specialists in the science of decision analysis . The recommendations of each guideline are therefore considered valid at the time of composition based on the data available . New developments in medical research and practice pertinent to each guideline will be review ed at a time established and indicated at publication to assure continued validity . The recommendations made are based on the level of evidence found . Grade A recommendations imply that there is consistent level 1 evidence ( r and omized controlled trials ) , grade B indicates that the evidence would be level 2 or 3 , which are cohort studies or case – control studies . Grade C recommendations are based on level 4 studies , meaning case series or poor- quality cohort studies , and grade D recommendations are based on level 5 evidence , meaning expert opinion Background Probiotics confer health benefits to the host . However , its clinical effect on irritable bowel syndrome ( IBS ) is controversial . Aims This study was aim ed to evaluate the effects of Saccharomyces boulardii on quality of life ( QOL ) and symptoms in patients with diarrhea-predominant IBS or mixed-type IBS . Methods Sixty-seven patients with IBS were r and omized either to receive S. boulardii at 2 × 1011 live cells as a daily dose ( n=34 ) , or placebo ( n=33 ) for 4 weeks . IBS-QOL was assessed at the beginning and end of the treatment phase . IBS-related symptoms , bowel movement frequency , and stool consistency were recorded on a daily basis and assessed each week . Results The overall improvement in IBS-QOL was higher in S. boulardii group than placebo ( 15.4 % vs 7.0 % ; P<0.05 ) . All eight domains of IBS-QOL were significantly improved in S. boulardii group ; however , placebo group only showed improvements in dysphoria and health worry . Composite scores for IBS symptoms were significantly reduced in both groups to a similar extent . Bowel frequency and stool consistency did not change in either group . Conclusions S. boulardii improved IBS-QOL better than placebo but was not superior for individual symptoms in patients with diarrhea-predominant IBS or mixed-type IBS BACKGROUND Seventy percent of Crohn 's disease ( CD ) patients exhibit anastomotic recurrence within 1 year after ileo-caecal surgery . Recent clinical trials suggest the beneficial use of probiotics in the control of intestinal inflammation in pouchitis and ulcerative colitis . This study is a multicenter clinical trial evaluating the efficacy of an oral administration of the probiotic LAl on early post-operative endoscopic recurrence of CD . METHODS Seventy patients with CD were enrolled prior to elective ileo-caecal resection and r and omly assigned after surgery to daily treatment with either Lactobacillus johnsonii , LA1 , Nestle ( 1010 colony-forming units , CFU ) ( group A , n = 34 ) or placebo ( group B , n = 36 ) for 12 weeks . The primary objective was to assess the effect of LAl on the endoscopic recurrence rate at 12 weeks . Stratification was performed according to smoking status at r and omization . RESULTS Seven and 14 patients were excluded in the LA1 and placebo groups , respectively . In intention-to-treat analysis , the mean endoscopic score was not significantly different between the two treatment groups at 3 months ( LA1 versus placebo : 1.50 + /- 1.32 versus 1.22+/-1.37 , treatment effect : P = 0.48 , smoke effect : P = 0.72 ) . The percentage of patients with severe recurrence ( i3 + i4 ) was 21 % and 15 % in the LAl and placebo groups , respectively ( P = 0.33 ) . Using a per- protocol ( PP ) analysis , the mean endoscopic score was not significantly different between the two treatment groups ( LAl versus placebo groups : 1.44 + /-1.31 versus 1.05 + /- 1.21 , P = 0.32 ) . The percentage of patients with severe recurrence ( i3 + i4 ) was 19 % and 9 % in the LAl and placebo groups , respectively ( P = 0.054 ) . Clinical relapse rate ( CDAI [ CD activity index ] > 150 , with an increase of CDAI > 70 points or greater from baseline ) in the LAl and placebo groups was 15 % ( 4/27 ) and 13.5 % ( 3/22 ) , respectively ( PP analysis : chi-square test , P = 0.91 and log-rank test : P = 0.79 ) . CONCLUSION Oral administration of the probiotic LA1 in patients with CD failed to prevent early endoscopic recurrence at 12 weeks after ileo-caecal resection AIM To evaluate the effectiveness of probiotic therapy for suppressing relapse in patients with inactive ulcerative colitis ( UC ) . METHODS Bio-Three tablets , each containing 2 mg of lactomin ( Streptococcus faecalis T-110 ) , 10 mg of Clostridium butyricum TO-A , and 10 mg of Bacillus mesentericus TO-A , were used as probiotic therapy . Sixty out patients with UC in remission were r and omly assigned to receive 9 Bio-Three tablets/day ( Bio-Three group ) or 9 placebo tablets/day ( placebo group ) for 12 mo in addition to their ongoing medications . Clinical symptoms were evaluated monthly or on the exacerbation of symptoms or need for additional medication . Fecal sample s were collected to analyze bacterial DNA at baseline and 3-mo intervals . Terminal restriction fragment length polymorphism and cluster analyses were done to examine bacterial components of the fecal microflora . RESULTS Forty-six patients , 23 in each group , completed the study , and 14 were excluded . The relapse rates in the Bio-Three and placebo groups were respectively 0.0 % vs 17.4 % at 3 mo ( P = 0.036 ) , 8.7 % vs 26.1 % at 6 mo ( P = 0.119 ) , and 21.7 % vs 34.8 % ( P = 0.326 ) at 9 mo . At 12 mo , the remission rate was 69.5 % in the Bio-Three group and 56.6 % in the placebo group ( P = 0.248 ) . On cluster analysis of fecal flora , 7 patients belonged to cluster I , 32 to cluster II , and 7 to cluster III . CONCLUSION Probiotics may be effective for maintaining clinical remission in patients with quiescent UC , especially those who belong to cluster I on fecal bacterial analysis BACKGROUND AND AIM We conducted a r and omized , double-blinded , placebo-controlled trial to investigate the efficacy of Bifidobacterium longum 536 ( BB536 ) supplementation for induction of remission in Japanese patients with active ulcerative colitis ( UC ) . METHODS Fifty-six patients with mild to moderate UC were enrolled . Three patients had pancolitis , 36 had left-sided colitis , and 17 had proctitis . Patients were r and omly treated with 2 - 3 × 10(11 ) freeze-dried viable BB536 ( 28 patients ) or placebo ( 28 patients ) for 8 weeks . RESULTS In total , 63 % of patients receiving BB536 showed clinical remission ( UC disease activity index [ UCDAI ] ≤2 ) at week 8 compared to 52 % of those receiving placebo ( P = 0.395 ) . We observed a significant decrease of UCDAI scores ( 3.8 ± 0.4 at baseline to 2.6 ± 0.4 at week 8) in the BB536 group ( P < 0.01 ) , whereas there was no significant decrease in the placebo group ( P = 0.88 ) . There was also a significant decrease in the Rachmilewitz endoscopic index ( EI ) and the Mayo subscore at week 8 in the BB536 group , whereas there was no significant decrease in the placebo group . A single patient in the BB536 group complained of a mild side-effect , but no other adverse effects were observed . CONCLUSION Supplementation with BB536 was well tolerated and reduced UCDAI scores , EI and Mayo subscores after 8 weeks in Japanese patients with mild to moderately active UC BACKGROUND & AIMS Probiotics can maintain ulcerative colitis ( UC ) in remission effectively , but little is known of their ability to induce remission . We conducted a multicenter , r and omized , double-blind , placebo-controlled trial of a high-potency probiotic , VSL#3 , for the treatment of mild-to-moderately active UC . METHODS Adult patients with mild-to-moderate UC were assigned r and omly to groups that were given 3.6 x 10(12 ) CFU VSL#3 ( n = 77 ) or placebo ( n = 70 ) , twice daily for 12 weeks . The primary end point was a 50 % decrease in the Ulcerative Colitis Disease Activity Index ( UCDAI ) at 6 weeks . The secondary end points included remission by 12 weeks and reduction in total individual UCDAI parameters from baseline at 12 weeks . Intention-to-treat analysis was performed . RESULTS At week 6 , the percentage of patients with an improvement in UCDAI score that was greater than 50 % was significantly higher in the group given VSL#3 ( 25 ; 32.5 % ) than the group given placebo ( 7 ; 10 % ) ( P = .001 ) . At week 12 , there were 33 patients given VSL#3 ( 42.9 % ) who achieved remission , compared with 11 patients given placebo ( 15.7 % ) ( P < .001 ) . Furthermore , significantly more patients given VSL#3 ( 40 ; 51.9 % ) achieved a decrease in their UCDAI that was greater than 3 points , compared with those given placebo ( 13 ; 18.6 % ) ( P < .001 ) . The VSL#3 group had significantly greater decreases in UCDAI scores and individual symptoms at weeks 6 and 12 , compared with the placebo group . CONCLUSIONS VSL#3 is safe and effective in achieving clinical responses and remissions in patients with mild-to-moderately active UC Involvement of pathogenic or potentially pathogenic bacteria in the pathogenesis of inflammatory bowel disease has long been suggested because , among other reasons , the inflammatory response resembles that in infectious bowel diseases . Elevated antibody levels to pathogen antigens and a changed metabolic activity of the intestinal microflora have been detected in patients with Crohn 's disease . Several studies have revealed a possible etiologic link between intestinal microorganisms and inflammatory bowel disease . Therefore , several therapeutic strategies , including reduction or dilution of bacterial components in the intestine by antibiotics or intestinal lavage , respectively , inactivation of inflammatory bacterial products , and reconstitution of intestinal microflora have been employed , substantiating the idea that dysfunction of the intestinal mucosal barrier and an alteration of bacterial composition contribute to the inflammatory disease . However , the beneficial effect of restoration of the physiologic intestinal microflora in colonic inflammation by exogenous administration of a viable nonpathogenic bacterium has not been investigated before in a placebo-controlled study . Promising results came from the present pilot study in which the nonpathogenic Escherichia coli strain Nissle 1917 was tested for efficacy and tolerance in maintaining remission in patients with colonic Crohn 's disease . Application of the physiologic bacteria reduced the risk for relapse and minimized the need for glucocorticoids . Therefore we are convinced that in Crohn 's disease parts of the intestinal microflora , including the host 's immune response toward indigenous flora or an impairment of the gut flora 's metabolic activity are involved in the development or at least in the onset of relapse from remissive of colonic Crohn 's disease . However , more data are necessary to prove the benefit of E. coli strain Nissle 1917 as a new therapy to maintain remission of colonic Crohn 's disease BACKGROUND & AIMS Probiotic formulations of single species of bacteria have not been effective in preventing the recurrence of Crohn 's disease after surgery . We investigated the ability of VSL#3 , a mixture of 8 different bacterial probiotic species , to prevent Crohn 's disease recurrence after surgery in a multicenter , r and omized , double-blind , placebo-controlled trial . METHODS Within 30 days of ileocolonic resection and re-anastomosis , patients with Crohn 's disease were r and omly assigned to groups given 1 sachet of VSL#3 ( 900 billion viable bacteria , comprising 4 strains of Lactobacillus , 3 strains of Bifidobacterium , and 1 strain of Streptococcus salivarius subspecies thermophilus ) ( n = 59 ) or matching placebo ( n = 60 ) . Colonoscopy was performed at days 90 and 365 to evaluate the neoterminal ileum for disease recurrence and obtain mucosal biopsies for cytokine analysis . Patients from both groups with either no or mild endoscopic recurrence at day 90 received VSL#3 until day 365 . The primary outcome was the proportion of patients with severe endoscopic recurrence at day 90 . RESULTS At day 90 , the proportion of patients with severe endoscopic lesions did not differ significantly between VSL#3 ( 9.3 % ) and placebo ( 15.7 % , P = .19 ) . The proportions of patients with non-severe lesions at day 90 who had severe endoscopic recurrence at day 365 were 10.0 % in the early VSL#3 group ( given VSL#3 for the entire 365 days ) and 26.7 % in the late VSL#3 group ( given VSL#3 from days 90 through 365 ) ( P = .09 ) . Aggregate rates of severe recurrence ( on days 90 and 365 ) were not statistically different , 20.5 % of subjects in the early VSL#3 group and 42.1 % in the late VSL#3 group . Patients receiving VSL#3 had reduced mucosal inflammatory cytokine levels compared with placebo at day 90 ( P < .05 ) . Crohn 's disease activity index and inflammatory bowel disease quality of life scores were similar in the 2 groups . CONCLUSIONS There were no statistical differences in endoscopic recurrence rates at day 90 between patients who received VSL#3 and patients who received placebo . Lower mucosal levels of inflammatory cytokines and a lower rate of recurrence among patients who received early VSL#3 ( for the entire 365 days ) indicate that this probiotic should be further investigated for prevention of Crohn 's disease recurrence . Clinical trials.gov number : NCT00175292 BACKGROUND AND AIMS To investigate the clinical effect of treatment with Lactobacillus acidophilus La-5 and Bifidobacterium animalis subsp . lactis BB-12 ( Probio-Tec AB-25 ) to maintain remission in patients with ulcerative colitis . METHODS Patients with left-sided ulcerative colitis in remission - including proctitis and at least one relapse within the last year were r and omised ( 2:1 ) in a double-blind placebo-controlled study to Probio-Tec AB-25 or placebo for 52 weeks . The patients were evaluated clinical ly , endoscopically and histologically at entry and if relapsing . No other medication for ulcerative colitis than the study drug was allowed during the study . Primary endpoint was maintenance of clinical remission , secondary endpoints comparisons of days to relapse , and safety and tolerability of the study drug . The concentrations of the probiotic bacterial strains in stool were analysed in a subset of patients . RESULTS Thirty-two patients were r and omised . Twenty patients received Probio-Tec AB-25 and twelve patients received placebo . Five patients ( 25 % ) in the Probio-Tec AB-25 group and one patient ( 8 % ) in the placebo group maintained remission after 1 year of treatment ( p=0.37 ) . The median time to relapse was 125.5days ( range 11 - 391 days ) in the probiotic group and 104 days ( range 28 - 369 days ) in the placebo group respectively , ( p=0.683 ) . Probio-Tec AB-25 was overall well tolerated . CONCLUSIONS In this small r and omised placebo-controlled trial no significant clinical benefit of Probio-Tec AB-25 could be demonstrated in comparison with placebo for maintaining remission in patients with left-sided ulcerative colitis . A difference may be achieved in larger studies , but the clinical significance of this would be question able . This study was registered in Clinical Trial.gov ( NCT00268164 ) BACKGROUND Ulcerative colitis has been suggested to be caused by infection and there is circumstantial evidence linking Escherichia coli with the condition . Our aim was to find out whether the administration of a non-pathogenic strain of E. coli ( Nissle 1917 ) was as effective as mesalazine in preventing relapse of ulcerative colitis . We also examined whether the addition of E. coli to st and ard medical therapy increased the chance of remission of active ulcerative colitis . METHODS This was a single-centre , r and omised , double-dummy study in which 120 patients with active ulcerative colitis were invited to take part . 116 patients accepted ; 59 were r and omised to mesalazine and 57 to E. coli . All patients also received st and ard medical therapy together with a 1-week course of oral gentamicin . After remission , patients were maintained on either mesalazine or E. coli and followed up for a maximum of 12 months . A two-stage , conditional , intention-to-treat analysis was done . FINDINGS 44 ( 75 % ) patients in the mesalazine group attained remission compared with 39 ( 68 % ) in the E. coli group . Mean time to remission was 44 days ( median 42 ) in the mesalazine group and 42 days ( median 37 ) for those treated with E. coli . In the mesalazine group , 32 ( 73 % ) patients relapsed compared with 26 ( 67 % ) in the E. coli group . Mean duration of remission was 206 days in the mesalazine group ( median 175 ) and 221 days ( median 185 ) in the E. coli group . INTERPRETATION Our results suggest that treatment with a non-pathogenic E. coli has an equivalent effect to mesalazine in maintaining remission of ulcerative colitis . The beneficial effect of live E. coli may provide clues to the cause of ulcerative colitis Aminosalicylates are used as st and ard treatment for maintaining remission in ulcerative colitis . As yet , there is no other existing alternative with proven efficacy . In light of the hypothesis that the intestinal environment may contribute to the pathophysiology of ulcerative colitis , a trial was conducted to test the effects of probiotic treatment with an oral preparation of non‐pathogenic E. coli |
1,228 | 24,986,117 | The RE- AIM MDIC can be successfully applied to review ing literature in this context | Background Team ball sports such as soccer , basketball and volleyball have high participation levels worldwide .
Musculoskeletal injuries are common in team ball sports and are associated with significant treatment costs , participation loss and long-term negative side effects .
The results of recent r and omized controlled trials provide support for the protective effect of injury-prevention exercise programmes ( IPEPs ) in team ball sports , but also highlight that achieving adequate compliance can be challenging .
A key process in enhancing the ultimate impact of team ball sport IPEPs is identifying the specific implementation components that influence the adoption , execution and maintenance of these interventions .
Despite this , no systematic review focussing on the specific implementation components of team ball sport IPEPs has been conducted .
Objectives Our objective was to assess the reporting of specific implementation components in the published literature on team ball sport IPEPs using the Reach Efficacy Adoption Implementation Maintenance ( RE- AIM ) framework . | Background Players are the targeted end-users and beneficiaries of exercise-training programmes implemented during coach-led training sessions , and the success of programmes depends upon their active participation . Two variants of an exercise-training programme were incorporated into the regular training schedules of 40 community Australian Football teams , over two seasons . One variant replicated common training practice s , while the second was an evidence -based programme to alter biomechanical and neuromuscular factors related to risk of knee injuries . This paper describes the structure of the implemented programmes and compares players ’ end-of-season views about the programme variants . Methods This study was nested within a larger group-clustered r and omised controlled trial of the effectiveness of two exercise-training programmes ( control and neuromuscular control ( NMC ) ) for preventing knee injuries . A post-season self-report survey , derived from Health Belief Model constructs , included questions to obtain players ’ views about the benefits and physical challenges of the programme in which they participated . Results Compared with control players , those who participated in the NMC programme found it to be less physically challenging but more enjoyable and potentially of more benefit . Suggestions from players about potential improvements to the training programme and its future implementation included reducing duration , increasing range of drills/exercises and promoting its injury prevention and other benefits to players . Conclusions Players provide valuable feedback about the content and focus of implemented exercise-training programmes , that will directly inform the delivery of similar , or more successful , programmes in the future Background A protective effect on injury risk in youth sports through neuromuscular warm-up training routines has consistently been demonstrated . However , there is a paucity of information regarding the quantity and quality of coach-led injury prevention programmes and its impact on the physical performance of players . Objective The aim of this cluster-r and omised controlled trial was to assess whether different delivery methods of an injury prevention programme ( FIFA 11 + ) to coaches could improve player performance , and to examine the effect of player adherence on performance and injury risk . Method During the 2011 football season ( May – August ) , coaches of 31 tiers 1–3 level teams were introduced to the 11 + through either an unsupervised website or a coach-focused workshop with and without additional on-field supervisions . Playing exposure , adherence to the 11 + , and injuries were recorded for female 13-year-old to 18-year-old players . Performance testing included the Star Excursion Balance Test ( SEBT ) , single-leg balance , triple hop and jumping-over-a-bar tests . Results Complete preseason and postseason performance tests were available for 226 players ( 66.5 % ) . Compared to the unsupervised group , single-leg balance ( OR=2.8 ; 95 % CI 1.1 to 4.6 ) and the anterior direction of the SEBT improved significantly in the onfield supervised group of players ( OR=4.7 ; 95 % CI 2.2 to 7.1 ) , while 2-leg jumping performance decreased ( OR=−5.1 ; 95 % CI −9.9 to −0.2 ) . However , significant improvements in 5 of 6 reach distances in the SEBT were found , favouring players who highly adhered to the 11 + . Also , injury risk was lower for those players ( injury rate ratio , IRR=0.28 , 95 % CI 0.10 to 0.79 ) . Conclusions Different delivery methods of the FIFA 11 + to coaches influenced players ’ physical performance minimally . However , high player adherence to the 11 + result ed in significant improvements in functional balance and reduced injury risk Background Knee injuries in football are common regardless of age , gender or playing level , but adolescent females seem to have the highest risk . The consequences after severe knee injury , for example anterior cruciate ligament ( ACL ) injury , are well-known , but less is known about knee injury prevention . We have design ed a cluster r and omized controlled trial ( RCT ) to evaluate the effect of a warm-up program aim ed at preventing acute knee injury in adolescent female football . Methods In this cluster r and omized trial 516 teams ( 309 clusters ) in eight regional football districts in Sweden with female players aged 13–17 years were r and omized into an intervention group ( 260 teams ) or a control group ( 256 teams ) . The teams in the intervention group were instructed to do a structured warm-up program at two training sessions per week throughout the 2009 competitive season ( April to October ) and those in the control group were informed to train and play as usual . Sixty-eight sports physical therapists are assigned to the clubs to assist both groups in data collection and to examine the players ' acute knee injuries during the study period . Three different forms are used in the trial : ( 1 ) baseline player data form collected at the start of the trial , ( 2 ) computer-based registration form collected every month , on which one of the coaches/team leaders documents individual player exposure , and ( 3 ) injury report form on which the study therapists report acute knee injuries result ing in time loss from training or match play . The primary outcome is the incidence of ACL injury and the secondary outcomes are the incidence of any acute knee injury ( except contusion ) and incidence of severe knee injury ( defined as injury result ing in absence of more than 4 weeks ) . Outcome measures are assessed after the end of the 2009 season . Discussion Prevention of knee injury is beneficial for players , clubs , insurance companies , and society . If the warm-up program is proven to be effective in reducing the incidence of knee injury , it can have a major impact by reducing the future knee injury burden in female football as well as the negative long-term disabilities associated with knee injury . Trial registration Objective To assess the effect of a neuromuscular training program on the incidence of anterior cruciate ligament injuries in female team h and ball players . Design Prospect i ve intervention study . Setting Female team h and ball : Division I – III in Norway . Participants Players from the three top divisions : control season ( 1998–1999 ) , 60 teams ( 942 players ) ; first intervention season ( 1999–2000 ) , 58 teams ( 855 players ) ; second intervention season ( 2000–2001 ) , 52 teams ( 850 players ) . InterventionA five-phase program ( duration , 15 min ) with three different balance exercises focusing on neuromuscular control and planting/l and ing skills was developed and introduced to the players in the autumn of 1999 and revised before the start of the season in 2000 . The teams were instructed in the program and supplied with an instructional video , poster , six balance mats , and six wobble boards . Additionally , a physical therapist was attached to each team to follow up with the intervention program during the second intervention period . Main Outcome Measures The number of anterior cruciate ligament injuries during the three seasons and compliance with the program . Results There were 29 anterior cruciate ligament injuries during the control season , 23 injuries during the first intervention season ( OR , 0.87 ; CI , 0.50–1.52 ; p = 0.62 ) , and 17 injuries during the second intervention season ( OR , 0.64 ; CI , 0.35–1.18 ; p = 0.15 ) . In the elite division , there were 13 injuries during the control season , six injuries during the first intervention season ( OR , 0.51 ; CI , 0.19–1.35 ; p = 0.17 ) , and five injuries in the second intervention season ( OR , 0.37 ; CI , 0.13–1.05 ; p = 0.06 ) . For the entire cohort , there was no difference in injury rates during the second intervention season between those who complied and those who did not comply ( OR , 0.52 ; CI , 0.15–1.82 ; p = 0.31 ) . In the elite division , the risk of injury was reduced among those who completed the anterior cruciate ligament injury prevention program ( OR , 0.06 ; CI , 0.01–0.54 ; p = 0.01 ) compared with those who did not . Conclusions This study shows that it is possible to prevent anterior cruciate ligament injuries with specific neuromuscular training Background This study was conducted to investigate whether the most common injuries in soccer could be prevented , and to determine if a simple question naire could identify players at increased risk . Hypothesis Introduction of targeted exercise programs to male soccer players with a history of previous injury or reduced function in the ankle , knee , hamstring , or groin will prevent injuries . Study Design R and omized controlled trial ; Level of evidence , 2 . Methods A total of 508 players representing 31 teams were included in the study . A question naire indicating previous injury and /or reduced function as inclusion criteria was used to divide the players into high-risk ( HR ) ( 76 % ) and low-risk ( LR ) groups . The HR players were r and omized individually into an HR intervention group or HR control group . Results A total of 505 injuries were reported , sustained by 56 % of the players . The total injury incidence was a mean of 3.2 ( 95 % confidence interval [ CI ] , 2.5–3.9 ) in the LR control group , 5.3 ( 95 % Cl , 4.6–6.0 ) in the HR control group ( P = .0001 vs the LR control group ) , and 4.9 ( 95 % Cl , 4.3–5.6 ) in the HR intervention group ( P = .50 vs the HR control group ) . For the main outcome measure , the sum of injuries to the ankle , knee , hamstring , and groin , there was also a significantly lower injury risk in the LR control group compared with the 2 other groups , but no difference between the HR intervention group and the HR control group . Compliance with the training programs in the HR intervention group was poor , with only 27.5 % in the ankle group , 29.2 % in the knee group , 21.1 % in the hamstring group , and 19.4 % in the groin defined as having carried out the minimum recommended training volume . Conclusion The players with a significantly increased risk of injury were able to be identified through the use of a question naire , but player compliance with the training programs prescribed was low and any effect of the intervention on injury risk could not be detected Abstract . This prospect i ve r and omized intervention investigated whether training on a balance board could reduce the amount of traumatic injuries of the lower extremities in female soccer players . A total of 221 female soccer players from 13 different teams playing in the second and third Swedish divisions volunteered to participate in the study . Seven teams ( n=121 ) were r and omized to an intervention group and six teams ( n=100 ) to a control group and were followed during one outdoor season ( April – October ) . Before and after the season muscle flexibility and balance/postural sway of the lower extremities were measured in the players . There were no significant differences in age , height , weight , muscle flexibility and balance/postural sway of the lower extremities between the intervention and the control group . During the season the players in the intervention group performed a special training program consisting of 10–15 min of balance board training in addition to their st and ard soccer practice and games . After a 37 % drop-out the intervention group consisted of 62 players and the control group of 78 players . The results showed no significant differences between the groups with respect either to the number , incidence , or type of traumatic injuries of the lower extremities . The incidence rate of " major " injuries was higher in the intervention group than in the control group . Four of five anterior cruciate ligament injuries occurred in the intervention group , which means that we could not prevent severe knee injuries in female soccer players with balance board training . However , among the players who had been injured during the 3-month period prior to this investigation there were significantly more players from the control group than from the intervention group who sustained new injuries during the study period Objective To evaluate the effectiveness of neuromuscular training in reducing the rate of acute knee injury in adolescent female football players . Design Stratified cluster r and omised controlled trial with clubs as the unit of r and omisation . Setting 230 Swedish football clubs ( 121 in the intervention group , 109 in the control group ) were followed for one season ( 2009 , seven months ) . Participants 4564 players aged 12 - 17 years ( 2479 in the intervention group , 2085 in the control group ) completed the study . Intervention 15 minute neuromuscular warm-up programme ( targeting core stability , balance , and proper knee alignment ) to be carried out twice a week throughout the season . Main outcome measures The primary outcome was rate of anterior cruciate ligament injury ; secondary outcomes were rates of severe knee injury ( > 4 weeks ’ absence ) and any acute knee injury . Results Seven players ( 0.28 % ) in the intervention group , and 14 ( 0.67 % ) in the control group had an anterior cruciate ligament injury . By Cox regression analysis according to intention to treat , a 64 % reduction in the rate of anterior cruciate ligament injury was seen in the intervention group ( rate ratio 0.36 , 95 % confidence interval 0.15 to 0.85 ) . The absolute rate difference was −0.07 ( 95 % confidence interval −0.13 to 0.001 ) per 1000 playing hours in favour of the intervention group . No significant rate reductions were seen for secondary outcomes . Conclusions A neuromuscular warm-up programme significantly reduced the rate of anterior cruciate ligament injury in adolescent female football players . However , the absolute rate difference did not reach statistical significance , possibly owing to the small number of events . Trial registration Clinical trials NCT00894595 Background A recent study published in The American Journal of Sports Medicine showed that asymptomatic soccer players with an increased risk of developing Achilles and patellar tendon injuries within the next 12 months can be identified with use of ultrasonography . Hypothesis Prophylactic eccentric training and stretching can reduce both the frequency of asymptomatic ultrasonographic changes in Achilles and patellar tendons in soccer players and the risk of these asymptomatic intratendinous changes becoming symptomatic . Study Design R and omized controlled trial ; Level of evidence , 1 . Methods Two hundred and nine Danish professional soccer players from the best national league ( Super League ) were followed over 12 months with use of ultrasonography and injury registration . Half the teams were r and omized to an intervention group with prophylactic eccentric training and stretching of the Achilles and patellar tendons during the soccer season . Results The eccentric training and stretching did not reduce the injury risk , and , contrary to all expectations , the injury risk during the season was increased in players with abnormal patellar tendons at the beginning of the study in January . Eccentric training and stretching in players with normal patellar tendons significantly reduced the proportion of players with ultrasonographic changes in the patellar tendons at the end of the season ( risk difference [ RD ] = 12 % ; 95 % confidence interval [ CI ] , 2%–22 % ; P = .02 ) , but the training had no effect on the Achilles tendons ( RD = 1 % ; 95 % CI , −7 % to 9 % ; P = .75 ) . The presence of preseason ultrasonographic abnormalities in the tendons significantly increased the risk of developing tendon symptoms during the season ( relative risk = 1.9 ; 95 % CI , 1.2–3.1 ; P = .009 ) . Conclusions This study demonstrates that with the use of ultrasonography , tendon changes in soccer players can be diagnosed before they become symptomatic . The prophylactic eccentric training and stretching program reduces the risk of developing ultrasonographic abnormalities in the patellar tendons but has no positive effects on the risk of injury . On the contrary , in asymptomatic players with ultrasonographically abnormal patellar tendons , prophylactic eccentric training and stretching increased the injury risk Background Participants ' compliance , attitudes and beliefs have the potential to influence the efficacy of an intervention greatly . Objective To characterise team and player compliance with a comprehensive injury prevention warm-up programme for football ( The 11 + ) , and to assess attitudes towards injury prevention among coaches and their association with compliance and injury risk . Study Design A prospect i ve cohort study and retrospective survey based on a cluster-r and omised controlled trial with teams as the unit of r and omisation . Methods Compliance , exposure and injuries were registered prospect ively in 65 of 125 football teams ( 1055 of 1892 female Norwegian players aged 13–17 years and 65 of 125 coaches ) throughout one football season ( March – October 2007 ) . St and ardised telephone interviews were conducted to assess coaches ' attitudes towards injury prevention . Results Teams completed the injury prevention programme in 77 % ( mean 1.3 sessions per week ) of all training and match sessions , and players in 79 % ( mean 0.8 sessions per week ) of the sessions they attended . Compared with players with intermediate compliance , players with high compliance with the programme had a 35 % lower risk of all injuries ( RR 0.65 , 95 % CI 0.46 to 0.91 , p=0.011 ) . Coaches who had previously utilised injury prevention training coached teams with a 46 % lower risk of injury ( OR 0.54 , 95 % CI 0.33 to 0.87 , p=0.011 ) . Conclusions Compliance with the injury prevention programme was high , and players with high compliance had significantly lower injury risk than players with intermediate compliance . Positive attitudes towards injury prevention correlated with high compliance and lower injury risk Groin injuries cause major problems in sports and particularly in football . Exercise is effective in treating adductor-related groin pain , but no trials have been published regarding the specific prevention of groin pain or prevention specifically targeting overuse injuries in sport using exercise programs . We performed a cluster-r and omized trial including 55 football clubs representing 1211 players . The clubs were r and omized to an exercise program aim ed at preventing groin injuries ( n=27 ) or to a control group training as usual ( n=28 ) . The intervention program consisted of six exercises including strengthening ( concentric and eccentric ) , coordination , and core stability exercises for the muscles related to the pelvis . Physiotherapists assigned to each club registered all groin injuries . Twenty-two clubs in each group completed the study , represented by 977 players . There was no significant effect of the intervention ( HR=0.69 , 95 % CI 0.40 - 1.19 ) . The risk of a groin injury was reduced by 31 % , but this reduction was not significant . A univariate analysis showed that having had a previous groin injury almost doubles the risk of developing a new groin injury and playing at a higher level almost triples the risk of developing a groin injury The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement is used worldwide to improve the reporting of r and omized , controlled trials . Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . Background The incidence rate of soccer injuries is among the highest in sports , particularly for adult male soccer players . Purpose To investigate the effect of the ‘ The11 ’ injury prevention programme on injury incidence and injury severity in adult male amateur soccer players . Study design Cluster-r and omised controlled trial . Methods Teams from two high-level amateur soccer competitions were r and omly assigned to an intervention ( n=11 teams , 223 players ) or control group ( n=12 teams , 233 players ) . The intervention group was instructed to perform The11 in each practice session during one soccer season . The11 focuses on core stability , eccentric training of thigh muscles , proprioceptive training , dynamic stabilisation and plyometrics with straight leg alignment . All participants of the control group continued their practice sessions as usual . Results In total , 427 injuries were recorded , affecting 274 of 456 players ( 60.1 % ) . Compliance with the intervention programme was good ( team compliance=73 % , player compliance=71 % ) . Contrary to the hypothesis , injury incidences were almost equal between the two study groups : 9.6 per 1000 sports hours ( 8.4–11.0 ) for the intervention group and 9.7 ( 8.5–11.1 ) for the control group . No significant differences were found in injury severity , but a significant difference was observed in the location of the injuries : players in the intervention group sustained significantly less knee injuries . Conclusions This study did not find significant differences in the overall injury incidence or injury severity between the intervention and control group of adult male soccer players . More research is recommended , focusing on injury aetiology and risk factors in adult male amateur soccer players Background A soccer-specific balance training has been shown to decrease injury incidence of the anterior cruciate ligament and ankle sprains in r and omized controlled trials . However , hamstring injuries and tendinopathy remain significant issues in soccer . Hypothesis Proprioceptive training can reduce the incidence of hamstring muscle injuries and tendinopathy in elite soccer . There is a dose-effect relationship between balance training duration and injury incidence . Study Design Cohort study ; Level of evidence , 3 . Methods Twenty-four elite female soccer players ( body mass index , 21.7 ± 1.2 ; age , 21 ± 4 years ) of a German premier league soccer team were prospect ively included . Starting in January 2004 , an additional soccer-specific proprioceptive multistation training was initiated over 3 years . Injury data /1000 hours of exposure with documentation of all occurred injuries , detailed training , and match exposure data as well as time loss data were 100 % complete . Results At the end of the 3-year proprioceptive balance training intervention , noncontact hamstring injury rates were reduced from 22.4 to 8.2/1000 hours ( P = .021 ) , patellar tendinopathy from 3.0 to 1.0/1000 hours ( P = .022 ) , and Achilles tendinopathy from 1.5 to 0.0/1000 hours ( P = .035 ) . There was no effect of balance training on contact injuries . Mean time loss of all assessed injuries significantly decreased from 14.4 days during the control period to 1.5 days during intervention periods ( P = .003 ) . The more minutes of balance training performed , the lower the rate of overall injuries ( r = −0.185 , P = .001 ) , hamstring injuries ( r = −0.267 , P = .003 ) , patellar tendinopathy ( r = −0.398 , P = .02 ) , and gastrocnemius strains ( r = −0.342 , P = .002 ) . Conclusion Soccer-specific balance training ( protective balancing ) can reduce noncontact hamstring injuries and patellar and Achilles tendinopathy . A dose-effect relationship between duration of balance training and injury incidence is evident . A proprioceptive training program reduced the rehabilitation time in noncontact injuries , which warrants further investigation Objectives : To evaluate the cost effectiveness of a proprioceptive balance board training programme for the prevention of ankle sprains in volleyball . Methods : A total of 116 volleyball teams participated in this study which was carried out during the 2001–2002 volleyball season . Teams were r and omly allotted to an intervention group ( 66 teams , 628 players ) or a control group ( 52 teams , 494 players ) . Intervention teams followed a prescribed balance board training programme as part of their warm up . Control teams followed their normal training routine . An ankle sprain was recorded if it occurred as a result of volleyball and caused the subject to stop volleyball activity . The injured player completed a cost diary for the duration of the ankle sprain . Analyses were performed according to the intention to treat principle . Mean direct , indirect , and total costs were calculated and were compared between the two groups . Results : The total costs per player ( including the intervention material ) were significantly higher in the intervention group ( € 36.99 ( 93.87 ) ) than in the control group ( € 18.94 ( 147.09 ) ) . The cost of preventing one ankle sprain was approximately € 444.03 . Sensitivity analysis showed that a proprioceptive balance board training programme aim ed only at players with previous ankle sprains could be cost effective over a longer period of time . Conclusions : Positive effects of the balance board programme could only be achieved at certain costs . However , if broadly implemented , costs associated with the balance board programme would probably be lower Objective : To evaluate the effectiveness of a preseason physical training programme that taught l and ing and falling skills in improving l and ing skills technique and preventing injury in junior elite Australian football players . Methods : 723 male players who participated in an under 18 elite competition were studied prospect ively in a non-r and omised controlled trial over two consecutive football seasons . There were 114 players in the intervention group and 609 control players . The eight session intervention programme taught players six l and ing , falling , and recovery skills , which were considered fundamental for safe l and ing in Australian football . L and ing skills taught in these sessions were rated for competence by independent and blinded assessors at baseline and mid-season . Results : Evaluation of l and ing skills found no significant differences between the groups at baseline . Evaluation after the intervention revealed overall improvement in l and ing skills , but significantly greater improvement in the intervention group ( z = −7.92 , p = 0.001 ) . Players in the intervention group were significantly less likely ( relative rate 0.72 , 95 % confidence interval 0.52 to 0.98 ) to sustain an injury during the season than the control group . In particular , the time to sustaining a l and ing injury was significantly less for the intervention group ( relative rate 0.40 , 95 % confidence interval 0.17 to 0.92 ) compared with the control group . Conclusions : L and ing and falling ability can be taught to junior elite Australian football players . Players in the intervention group were protected against injury , particularly injuries related to l and ing and falls The Consoli date d St and ards of Reporting Trials ( CONSORT ) statement was developed to improve the reporting of r and omised controlled trials . It was initially published in 1996 and focused on the reporting of parallel group r and omised controlled trials . The statement was revised in 2001 , with a further up date in 2010 . A separate CONSORT statement for the reporting of abstract s was published in 2008 . In earlier papers we considered the implication s of the 2001 version of the CONSORT statement for the reporting of cluster r and omised trial . In this paper we provide up date d and extended guidance , based on the 2010 version of the CONSORT statement and the 2008 CONSORT statement for the reporting of abstract s. Background : Few authors have investigated the effectiveness of preventive intervention in European team h and ball . Purpose : The aim of the present study was to evaluate the effects of a prevention program on the incidence of injuries in female European team h and ball players . Study design : Prospect i ve controlled study . Methods : Ten female h and ball teams ( 134 players ) took part in the prevention program ( 1 . Information about injury mechanism , 2 . Balance-board exercises , 3 . Jump training ) while 10 other teams ( 142 players ) were instructed to train as usual . Over one season all injuries were documented weekly . Results : Ankle sprain was the most frequent diagnosis in both groups with 11 ankle sprains in the control group and 7 ankle sprains in the intervention group ( Odds ratio : 0.55 , 95 % confidence interval : 0.22–1.43 ) . The knee was the second frequent injury site . In the control group 5 of all knee injuries were anterior cruciate ligament ( ACL ) ruptures ( incidence : 0.21 per 1000 h ) in comparison with one in the intervention group ( incidence : 0.04 per 1000 h ) . Odds ratio was 0.17 with 95 % confidence interval of 0.02–1.5 . Conclusions : This study confirms that proprioceptive and neuromuscular training is appropriate for the prevention of knee and ankle injuries among female European team h and ball players Background Ankle sprains are the most common injuries in a variety of sports . Hypothesis A proprioceptive balance board program is effective for prevention of ankle sprains in volleyball players . Study Design Prospect i ve controlled study . Methods There were 116 male and female volleyball teams followed prospect ively during the 2001 - 2002 season . Teams were r and omized by 4 geographical regions to an intervention group ( 66 teams , 641 players ) and control group ( 50 teams , 486 players ) . Intervention teams followed a prescribed balance board training program ; control teams followed their normal training routine . The coaches recorded exposure on a weekly basis for each player . Injuries were registered by the players within 1 week after onset . Results Significantly fewer ankle sprains in the intervention group were found compared to the control group ( risk difference = 0.4/1000 playing hours ; 95 % confidence interval , 0.1 - 0.7 ) . A significant reduction in ankle sprain risk was found only for players with a history of ankle sprains . The incidence of overuse knee injuries for players with history of knee injury was increased in the intervention group . History of knee injury may be a contraindication for proprioceptive balance board training . Conclusions Use of proprioceptive balance board program is effective for prevention of ankle sprain recurrences Objectives : To assess in a single team of Australian Rules football players the effect of a specific intervention program on the incidence and consequence of hamstring muscle strain injuries . Method : A prospect i ve study was performed with a single team being followed for four playing seasons for hamstring injury . Magnetic resonance imaging was used to confirm the diagnosis of hamstring muscle injury . After two playing seasons an intervention program was implemented with the number of athletes with hamstring injury , competition days missed , and incidence of hamstring match injuries per 1000 h of playing time being compared pre- and post-intervention . The intervention program involved stretching whilst fatigued , sport specific training drills , and an emphasis on increasing the amount of high intensity anaerobic interval training . Results : In the seasons prior to the intervention , nine and 11 athletes sustained hamstring injury compared to two and four following intervention . Competition days missed reduced from 31 and 38 to 5 and 16 following intervention and match incidence decreased from 4.7 to 1.3 per 1000 h of playing time . A beneficial effect was demonstrated with a smaller number of players having hamstring injuries ( p = 0.05 ) , a lower number of competition games missed being recorded ( p<0.001 ) , and a decrease in hamstring strain incidence per 1000 h of playing time ( p = 0.01 ) following the intervention program . Conclusions : Increasing the amount of anaerobic interval training , stretching whilst the muscle is fatigued , and implementing sport specific training drills result ed in a significant reduction in the number and consequences of hamstring muscle strain injuries Objective To examine the effect of a comprehensive warm-up programme design ed to reduce the risk of injuries in female youth football . Design Cluster r and omised controlled trial with clubs as the unit of r and omisation . Setting 125 football clubs from the south , east , and middle of Norway ( 65 clusters in the intervention group ; 60 in the control group ) followed for one league season ( eight months ) . Participants 1892 female players aged 13 - 17 ( 1055 players in the intervention group ; 837 players in the control group ) . Intervention A comprehensive warm-up programme to improve strength , awareness , and neuromuscular control during static and dynamic movements . Main outcome measure Injuries to the lower extremity ( foot , ankle , lower leg , knee , thigh , groin , and hip ) . Results During one season , 264 players had relevant injuries : 121 players in the intervention group and 143 in the control group ( rate ratio 0.71 , 95 % confidence interval 0.49 to 1.03 ) . In the intervention group there was a significantly lower risk of injuries overall ( 0.68 , 0.48 to 0.98 ) , overuse injuries ( 0.47 , 0.26 to 0.85 ) , and severe injuries ( 0.55 , 0.36 to 0.83 ) . Conclusion Though the primary outcome of reduction in lower extremity injury did not reach significance , the risk of severe injuries , overuse injuries , and injuries overall was reduced . This indicates that a structured warm-up programme can prevent injuries in young female football players . Trial registration IS RCT N10306290 Abstract Objective To investigate the effect of a structured warm-up programme design ed to reduce the incidence of knee and ankle injuries in young people participating in sports . Design Cluster r and omised controlled trial with clubs as the unit of r and omisation . Setting 120 team h and ball clubs from central and eastern Norway ( 61 clubs in the intervention group , 59 in the control group ) followed for one league season ( eight months ) . Participants 1837 players aged 15 - 17 years ; 958 players ( 808 female and 150 male ) in the intervention group ; 879 players ( 778 female and 101 male ) in the control group . Intervention A structured warm-up programme to improve running , cutting , and l and ing technique as well as neuromuscular control , balance , and strength . Main outcome measure The rate of acute injuries to the knee or ankle . Results During the season , 129 acute knee or ankle injuries occurred , 81 injuries in the control group ( 0.9 ( SE 0.09 ) injuries per 1000 player hours ; 0.3 ( SE 0.17 ) in training v 5.3 ( SE 0.06 ) during matches ) and 48 injuries in the intervention group ( 0.5 ( SE 0.11 ) injuries per 1000 player hours ; 0.2 ( SE 0.18 ) in training v 2.5 ( SE 0.06 ) during matches ) . Fewer injured players were in the intervention group than in the control group ( 46 ( 4.8 % ) v ( 76 ( 8.6 % ) ; relative risk intervention group v control group 0.53 , 95 % confidence interval 0.35 to 0.81 ) . Conclusion A structured programme of warm-up exercises can prevent knee and ankle injuries in young people playing sports . Preventive training should therefore be introduced as an integral part of youth sports programmes PURPOSE To investigate the effectiveness of a multistation proprioceptive exercise program for the prevention of ankle injuries in basketball players using a prospect i ve r and omized controlled trial in combination with biomechanical tests of neuromuscular performance . METHODS A total of 232 players participated in the study and were r and omly assigned to a training or control group following the CONSORT statement . The training group performed a multistation proprioceptive exercise program , and the control group continued with their normal workout routines . During one competitive basketball season , the number of ankle injuries was counted and related to the number of sports participation sessions using logistic regression . Additional biomechanical pre – post tests ( angle reproduction and postural sway ) were performed in both groups to investigate the effects on neuromuscular performance . RESULTS In the control group , 21 injuries occurred , whereas in the training group , 7 injuries occurred . The risk for sustaining an ankle injury was significantly reduced in the training group by approximately 65 % . [ corrected ] The corresponding number needed to treat was 7 . Additional biomechanical tests revealed significant improvements in joint position sense and single-limb stance in the training group . CONCLUSIONS The multistation proprioceptive exercise program effectively prevented ankle injuries in basketball players . Analysis of number needed to treat clearly showed the relatively low prevention effort that is necessary to avoid an ankle injury . Additional biomechanical tests confirmed the neuromuscular effect and confirmed a relationship between injury prevention and altered neuromuscular performance . With this knowledge , proprioceptive training may be optimized to specifically address the dem and s in various athletic activities Background Ankle sprains are frequent injuries in soccer . Several strategies can be used to prevent further ankle sprains in athletes : the most common are proprioceptive training , strength training , and orthoses . Objective To investigate which of these 3 interventions is the most effective in preventing ankle sprains in athletes with previous ankle inversion sprain . Study Design R and omized controlled trial ; Level of evidence , 1 . Methods and Measures Eighty male soccer players ( age , 24.6 ± 2.63 years ; height , 175.60 ± 4.36 cm ; weight , 64.26 ± 8.37 kg ) in the first division of a men 's league who had experienced previous ankle inversion sprain were r and omly selected from an original population of 120 players . The subjects were individually and r and omly assigned to 4 study groups : group 1 ( n = 20 ) followed the proprioceptive program , group 2 ( n = 20 ) followed the strength program , group 3 ( n = 20 ) used orthoses , and group 4 ( n = 20 ) was the control group . Data on the frequency of ankle sprain reinjury were collected at the end of the session . Results There were no significant differences among the groups in the number of exposures . The incidence of ankle sprains in players in the proprioception training group was significantly lower than in the control group ( relative risk of injury , 0.13 ; 95 % confidence interval , 0.003 - 0.93 ; P = .02 ) . The findings with respect to the strength and orthotic groups in comparison with the control group were not significant ( relative risk of injury , 0.5 ; 95 % confidence interval , 0.11 - 1.87 ; P = .27 for strength ; relative risk of injury , 0.25 ; 95 % confidence interval , 0.03 - 1.25 ; P = .06 for orthotic group ) . Conclusion Proprioceptive training , compared with no intervention , was an effective strategy to reduce the rate of ankle sprains among male soccer players who suffered ankle sprain Background : Risk factors for soccer injuries and possibilities for prevention have been discussed by several authors , but only a few have investigated the effectiveness of preventive interventions . Purpose : The aim of the present study was to evaluate the effects of a prevention program on the incidence of soccer injuries in male youth amateur players . Study Design : Prospect i ve controlled intervention study . Methods : Seven soccer teams took part in a prevention program that focused on education and supervision of coaches and players , while seven other teams were instructed to train and play soccer as usual . Over 1 year all injuries were documented weekly by physicians . Complete weekly injury reports were available for 194 players . Results : The incidence of injury per 1000 hours of training and playing soccer was 6.7 in the intervention group and 8.5 in the control group , which equates to 21 % fewer injuries in the intervention group . The greatest effects were observed for mild injuries , overuse injuries , and injuries incurred during training . The prevention program had greater effects in low-skill than in high-skill teams . Conclusions : The incidence of soccer injuries can be reduced by preventive interventions , especially in low skill level youth teams . Coaches and players need better education regarding injury prevention strategies and should include such interventions as part of their regular training A set of exercises -- the " 11"--have been selected to prevent football injuries . The purpose of this cluster-r and omized controlled trial was to investigate the effect of the " 11 " on injury risk in female youth football . Teams were r and omized to an intervention ( n=59 teams , 1091 players ) or a control group ( n=54 teams , 1001 players ) . The intervention group was taught the " 11 , " exercises for core stability , lower extremity strength , neuromuscular control and agility , to be used as a 15-min warm-up program for football training over an 8-month season . A total of 396 players ( 20 % ) sustained 483 injuries . No difference was observed in the overall injury rate between the intervention ( 3.6 injuries/1000 h , confidence interval ( CI ) 3.2 - 4.1 ) and control group ( 3.7 , CI 3.2 - 4.1 ; RR=1.0 , CI 0.8 - 1.2 ; P=0.94 ) nor in the incidence for any type of injury . During the first 4 months of the season , the training program was used during 60 % of the football training sessions , but only 14 out of 58 intervention teams completed more than 20 prevention training sessions . In conclusion , we observed no effect of the injury prevention program on the injury rate , most likely because the compliance with the program was low Objective : To examine the effectiveness of a sport-specific balance training program in reducing injury in adolescent basketball . Design : Cluster r and omized controlled trial . Setting : Twenty-five high schools in Calgary and surrounding area . Subjects : Nine hundred and twenty high school basketball players ( ages 12 - 18 ) . Intervention : Subjects were r and omly allocated by school to the control ( n = 426 ) and training group ( n = 494 ) . Both groups were taught a st and ardized warm-up program . The training group was also taught an additional warm-up component and a home-based balance training program using a wobble board . Main Outcome Measures : All injuries occurring during basketball that required medical attention and /or caused a player to be removed from that current session and /or miss a subsequent session were then recorded and assessed by a team therapist who was blinded to training group allocation . Results : A basketball-specific balance training program was protective of acute-onset injuries in high school basketball [ RR = 0.71 ( 95 % CI ; 0.5 - 0.99 ) ] . The protective effect found with respect to all injury [ RR = 0.8 ( 95 % CI ; 0.57 - 1.11 ) ] , lower-extremity injury [ RR = 0.83 ( 95 % CI ; 0.57 - 1.19 ) ] , and ankle sprain injury [ RR = 0.71 ( 95 % CI ; 0.45 - 1.13 ) ] were not statistically significant . Self-reported compliance to the intended home-based training program was poor ( 298/494 or 60.3 % ) . Conclusions : A basketball-specific balance training program was effective in reducing acute-onset injuries in high school basketball . There was also a clinical ly relevant trend found with respect to the reduction of all , lower-extremity , and ankle sprain injury . Future research should include further development of neuromuscular prevention strategies in addition to further evaluation of methods to increase compliance to an injury-prevention training program in adolescents The purpose was to test the effect of eccentric strength training and flexibility training on the incidence of hamstring strains in soccer . Hamstring strains and player exposure were registered prospect ively during four consecutive soccer seasons ( 1999 - 2002 ) for 17 - 30 elite soccer teams from Icel and and Norway . The first two seasons were used as baseline , while intervention programs consisting of warm-up stretching , flexibility and /or eccentric strength training were introduced during the 2001 and 2002 seasons . During the intervention seasons , 48 % of the teams selected to use the intervention programs . There was no difference in the incidence of hamstring strains between teams that used the flexibility training program and those who did not [ relative risk (RR)=1.53 , P=0.22 ] , nor was there a difference compared with the baseline data ( RR=0.89 , P=0.75 ) . The incidence of hamstring strains was lower in teams who used the eccentric training program compared with teams that did not use the program ( RR=0.43 , P=0.01 ) , as well as compared with baseline data for the same intervention teams ( RR=0.42 , P=0.009 ) . Eccentric strength training with Nordic hamstring lowers combined with warm-up stretching appears to reduce the risk of hamstring strains , while no effect was detected from flexibility training alone . These results should be verified in r and omized clinical trials OBJECTIVE To determine the effectiveness of coach-led neuromuscular warm-up on reducing lower extremity ( LE ) injuries in female athletes in a mixed-ethnicity , predominantly low-income , urban population . DESIGN Cluster r and omized controlled trial . SETTING Chicago public high schools . PARTICIPANTS Of 258 coaches invited to participate , 95 ( 36.8 % ) enrolled ( 1558 athletes ) . Ninety coaches and 1492 athletes completed the study . INTERVENTIONS We r and omized schools to intervention and control groups . We trained intervention coaches to implement a 20-minute neuromuscular warm-up . Control coaches used their usual warm-up . MAIN OUTCOME MEASURES Coach compliance was tracked by self-report and direct observation . Coaches reported weekly athlete exposures ( AEs ) and LE injuries causing a missed practice or game . Research assistants interviewed injured athletes . Injury rates were compared between the control and intervention groups using χ(2 ) and Fisher exact tests . Significance was set at P < .05 . Poisson regression analysis adjusted for clustering and covariates in an athlete subset reporting personal information ( n = 855 ; 57.3 % ) . RESULTS There were 28 023 intervention AEs and 22 925 control AEs . Intervention coaches used prescribed warm-up in 1425 of 1773 practice s ( 80.4 % ) . Intervention athletes had lower rates per 1000 AEs of gradual-onset LE injuries ( 0.43 vs 1.22 , P < .01 ) , acute-onset noncontact LE injuries ( 0.71 vs 1.61 , P < .01 ) , noncontact ankle sprains ( 0.25 vs 0.74 , P = .01 ) , and LE injuries treated surgically ( 0 vs 0.17 , P = .04 ) . Regression analysis showed significant incidence rate ratios for acute-onset noncontact LE injuries ( 0.33 ; 95 % CI , 0.17 - 0.61 ) , noncontact ankle sprains ( 0.38 ; 95 % CI , 0.15 - 0.98 ) , noncontact knee sprains ( 0.30 ; 95 % CI , 0.10 - 0.86 ) , and noncontact anterior cruciate ligament injuries ( 0.20 ; 95 % CI , 0.04 - 0.95 ) . CONCLUSION Coach-led neuromuscular warm-up reduces noncontact LE injuries in female high school soccer and basketball athletes from a mixed-ethnicity , predominantly low-income , urban population . TRIAL REGISTRATION CLINICAL TRIALS.ORG IDENTIFIER : NCT01092286 In a provocative statement in a very recent issue of the American Journal of Preventive Medicine , Kessler and Glasgow have called for a 10-year moratorium on efficacy r and omised controlled trials ( RCTs ) in health and health services research .1 The authors argue that much intervention research has had minimal impact on both policy and practice because the very nature of efficacy studies means that focus has had to be on a limited number of specific causal and preventive factors ; this ignores both the complexity of real-world implementation and the multilevel ecological context in which interventions need to be conducted . I have also previously discussed those same limitations as they apply to sports injury prevention studies , 2 3 most recently as part of my keynote address at the 2011 International Olympic Committee World Conference on The Prevention of Injury and Illness in Sport , to be published in a forthcoming issue of BJSM .4 Compared with other areas of medical and behavioural research , sports medicine is in its infancy and intervention research of any a kind , efficacy or effectiveness , is relatively scarce , though the former dominates.5 It would not , therefore , be appropriate to halt all sports medicine efficacy studies or those using RCT design s. Recent review s in BJSM have highlighted clear gaps in current knowledge that could be useful for the prioritising of such work.6 7 Having said this , there is no doubt that unless we fully embrace the challenges of conducting implementation and translation/dissemination studies , our sports medicine prevention efforts Background : The incidence of acute hamstring injuries is high in several sports , including the different forms of football . Purpose : The authors investigated the preventive effect of eccentric strengthening of the hamstring muscles using the Nordic hamstring exercise compared with no additional hamstring exercise on the rate of acute hamstring injuries in male soccer players . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : Fifty Danish male professional and amateur soccer teams ( 942 players ) were allocated to an intervention group ( 461 players ) or a control group ( 481 players ) . Players in the intervention group conducted a 10-week progressive eccentric training program followed by a weekly seasonal program , whereas players in the control group followed their usual training program . The main outcome measures were numbers of overall , new , and recurrent acute hamstring injuries during 1 full soccer season . Results : Fifty-two acute hamstring injuries in the control group compared with 15 injuries in the intervention group were registered . Comparing intervention versus the control group , overall acute hamstring injury rates per 100 player seasons were 3.8 versus 13.1 ( adjusted rate ratio [ RR ] , 0.293 ; 95 % confidence interval [ CI ] , 0.150 - 0.572 ; P < .001 ) . New injury rates per 100 player seasons were 3.1 versus 8.1 ( RR , 0.410 ; 95 % CI , 0.180 - 0.933 ; P = .034 ) , whereas recurrent injury rates per 100 player seasons were 7.1 versus 45.8 ( RR , 0.137 ; 95 % CI , 0.037 - 0.509 ; P = .003 ) . Number needed to treat [ NNT ] to prevent 1 acute hamstring injury ( new or recurrent ) is 13 ( 95 % CI , 9 - 23 ) players . The NNT to prevent 1 new injury is 25 ( 95 % CI , 15 - 72 ) players , and NNT to prevent 1 recurrent injury is 3 ( 95 % CI , 2 - 6 ) players . Conclusion : In male professional and amateur soccer players , additional eccentric hamstring exercise decreased the rate of overall , new , and recurrent acute hamstring injuries Background Neuromuscular and proprioceptive training programs can decrease noncontact anterior cruciate ligament injuries ; however , they may be difficult to implement within an entire team or the community at large . Hypothesis A simple on-field alternative warm-up program can reduce noncontact ACL injuries . Study Design R and omized controlled trial ( clustered ) ; Level of evidence , 1 . Methods Participating National Collegiate Athletic Association Division I women 's soccer teams were assigned r and omly to intervention or control groups . Intervention teams were asked to perform the program 3 times per week during the fall 2002 season . All teams reported athletes ’ participation in games and practice s and any knee injuries . Injury rates were calculated based on athlete exposures , expressed as rate per 1000 athlete exposures . A z statistic was used for rate ratio comparisons . Results Sixty-one teams with 1435 athletes completed the study ( 852 control athletes ; 583 intervention ) . The overall anterior cruciate ligament injury rate among intervention athletes was 1.7 times less than in control athletes ( 0.199 vs 0.340 ; P = .198 ; 41 % decrease ) . Noncontact anterior cruciate ligament injury rate among intervention athletes was 3.3 times less than in control athletes ( 0.057 vs 0.189 ; P = .066 ; 70 % decrease ) . No anterior cruciate ligament injuries occurred among intervention athletes during practice versus 6 among control athletes ( P = .014 ) . Game-related noncontact anterior cruciate ligament injury rates in intervention athletes were reduced by more than half ( 0.233 vs 0.564 ; P = .218 ) . Intervention athletes with a history of anterior cruciate ligament injury were significantly less likely to suffer another anterior cruciate ligament injury compared with control athletes with a similar history ( P = .046 for noncontact injuries ) . Conclusion This program , which focuses on neuromuscular control , appears to reduce the risk of anterior cruciate ligament injuries in collegiate female soccer players , especially those with a history of anterior cruciate ligament injury There are 300,000 to 1,215,000 high-school football injuries each year in the United States . These injuries have an important effect on player participation and health care costs . This study investigates what portion of injuries occur during the third quarter of a game , and if completing a warm-up and stretching routine after halftime reduces the incidence of third-quarter injuries . Intervention-group teams participated in a prescribed three-minute warm-up and stretching routine following the halftime break . The control group received no warm-up and stretching intervention . Fifty-five games with 108 total injuries were examined . Overall , ligament sprains and muscle strains were the most common type of injury ( 38 % ) . In the nonintervention group , injuries occurred most often in the third quarter . Intervention teams sustained significantly fewer third-quarter sprains and strains per game ( p less than 0.05 ) , although no significant difference in total third-quarter injuries was noted . These findings suggest an association between post-halftime warm-up and stretching and reduced third-quarter sprain and strain injuries . We suggest a larger-scale , r and omized confirmatory study BACKGROUND Studies have suggested that exercise programs can reduce the incidence of noncontact injuries of the anterior cruciate ligament in female athletes . We conducted a two-year prospect i ve study to assess the effects of a knee ligament injury prevention exercise program on the incidence of noncontact anterior cruciate ligament injuries in high-school female athletes . METHODS A prospect i ve cohort design was used to study high-school female athletes ( playing soccer , basketball , and volleyball ) from fifteen schools ( 112 teams ) for two consecutive seasons . The schools were divided into treatment and control groups . The treatment group participated in a plyometric-based exercise program twice a week throughout the season . Practice and game exposures and compliance with the exercise program were recorded on a weekly basis . Suspected noncontact anterior cruciate ligament injuries were confirmed on the basis of the history as well as at the time of surgery and /or with magnetic resonance imaging . RESULTS A total of 1439 athletes ( 862 in the control group and 577 in the treatment group ) were monitored . There were six confirmed noncontact anterior cruciate ligament injuries : three in the treatment group , and three in the control group . The incidence of noncontact anterior cruciate ligament injuries per 1000 exposures was 0.167 in the treatment group and 0.078 in the control group , yielding an odds ratio of 2.05 , which was not significant ( p > 0.05 ) . CONCLUSIONS Our results suggest that a twenty-minute plyometric-based exercise program that focuses on the mechanics of l and ing from a jump and deceleration when running performed twice a week throughout the season will not reduce the rate of noncontact anterior cruciate ligament injuries in high-school female athletes Hamstring injuries are the most common injury sustained by Australian Football players . Eccentric training has been proposed as a potential preventative strategy . This pilot r and omised controlled trial ( RCT ) evaluated the effectiveness of a pre-season eccentric training program for preventing hamstring injuries at the community level of Australian Football . Seven amateur clubs ( n=220 players ) were recruited . Players were r and omised within clubs to the intervention ( eccentric exercise ) or control ( stretching ) groups and r and omisation was stratified according to previous history of hamstring injury . Five exercise sessions were completed over a 12-week period , three during the pre-season and two during the first 6 weeks of the season . Compliance was recorded and players were monitored for the season to collect injury and participation data . There was no difference between the control ( n=106 ) or intervention ( n=114 ) groups with respect to baseline characteristics . Only 46.8 % of all players completed at least two program sessions . Compliance was poorest for the intervention group . Intention-to-treat analysis suggested that players in the intervention group were not at reduced risk of hamstring injury ( RR 1.2 , 95 % CI : 0.5 , 2.8 ) . When only control and intervention group players who participated in at least the first two sessions were analysed , 4.0 % of intervention and 13.2 % of control group players sustained a hamstring injury ( RR 0.3 , 95 % CI : 0.1 , 1.4 ; p=0.098 ) . The findings suggest that a simple program of eccentric exercise could reduce the incidence of hamstring injuries in Australian Football but widespread implementation of this program is not likely because of poor compliance INTRODUCTION The prevention of injuries in all sports calls for a structured plan . The plan consists , as earlier described , of four steps . We have previously presented studies incorporating all four steps . The studies have shown that it is possible to prevent most injuries in young female players in European h and ball by applying a training programme combining the use of an ankle disc with functional strength training . In the previous studies we were not able to discriminate whether the preventive effect was due to the functional strength training or the training with the ankle disc . The aim of this study was to compare a programme with ankle disc and functional strength training with a programme with functional strength training only . METHODS Twenty h and ball teams were asked to participate , and 16 of 20 h and ball teams agreed to participate . The teams were cluster r and omised to either the programme with or without an ankle disc . RESULTS The group using the programme without the ankle disc had a significantly higher number of traumatic injuries ( 16 vs. 6 ) . The incidences of traumatic injuries in the ankle disc group were 2.4 ( 95 % CI 0.7 ; 6.2 ) injuries per 1000 h of match and 0.2 ( 95 % CI 0.02 ; 0.7 ) injuries per 1000 h of practice . In the group without ankle disc the incidences were 6.9 ( 95 % CI 3.3 ; 12.7 ) injuries per 1000 h of match and 0.6 ( 95 % CI 0.2 ; 1.3 ) injuries per 1000 h of practice . A significantly higher multivariate odds ratio ( 4.8 ) was found in the group not using the ankle disc . In addition the group using the ankle disc had significantly fewer moderate and major injuries . CONCLUSION By adding ankle disc training to a training programme with functional strength training , it is possible to reduce the number of injuries significantly , especially the number of moderate and major injuries Background Soccer is a leading sport for participation and injury in youth . Objective To examine the effectiveness of a neuromuscular prevention strategy in reducing injury in youth soccer players . Design Cluster-r and omised controlled trial . Setting Calgary soccer clubs ( male or female , U13–U18 , tier 1–2 , indoor soccer ) . Participants Eighty-two soccer teams were approached for recruitment . Players from 60 teams completed the study ( 32 training ( n=380 ) , 28 control ( n=364 ) ) . Intervention The training programme was a soccer-specific neuromuscular training programme including dynamic stretching , eccentric strength , agility , jumping and balance ( including a home-based balance training programme using a wobble board ) . The control programme was a st and ardised warm-up ( static and dynamic stretching and aerobic components ) and a home-based stretching programme . Main outcome measures Previously vali date d injury surveillance included injury assessment by a study therapist . The injury definition was soccer injury result ing in medical attention and /or removal from a session and /or time loss . Results The injury rate in the training group was 2.08 injuries/1000 player-hours , and in the control group 3.35 injuries/1000 player-hours . Based on Poisson regression analysis , adjusted for clustering by team and covariates , the incidence rate ratios ( IRR ) for all injuries and acute onset injury were 0.62 ( 95 % CI 0.39 to 0.99 ) and 0.57 ( 95 % CI 0.35 to 0.91 ) . Point estimates also suggest protection of lower extremity , ankle and knee sprain injuries ( IRR=0.68 ( 95 % CI 0.42 to 1.11 ) , IRR=0.5 ( 95 % CI 0.24 to 1.04 ) and IRR=0.38 ( 95 % CI 0.08 to 1.75 ) ) . Conclusions A neuromuscular training programme is protective of all injuries and acute onset injury in youth soccer players The primary purpose of this study was to evaluate whether a preseason strength training programme for the hamstring muscle group - emphasising eccentric overloading - could affect the occurrence and severity of hamstring injuries during the subsequent competition season in elite male soccer players . Thirty players from two of the best premier-league division teams in Sweden were divided into two groups ; one group received additional specific hamstring training , whereas the other did not . The extra training was performed 1 - 2 times a week for 10 weeks by using a special device aim ing at specific eccentric overloading of the hamstrings . Isokinetic hamstring strength and maximal running speed were measured in both groups before and after the training period and all hamstring injuries were registered during the total observational period of 10 months . The results showed that the occurrence of hamstring strain injuries was clearly lower in the training group ( 3/15 ) than in the control group ( 10/15 ) . In addition , there were significant increases in strength and speed in the training group . However , there were no obvious coupling between performance parameters and injury occurrence . These results indicate that addition of specific preseason strength training for the hamstrings - including eccentric overloading - would be beneficial for elite soccer players , both from an injury prevention and from performance enhancement point of view PURPOSE This panel-r and omized intervention trial was design ed to examine the effect of a motor control training program for elite Australian Football League players with and without low back pain ( LBP ) . METHODS The outcome measures included cross-sectional area ( CSA ) and symmetry of multifidus , quadratus lumborum , and psoas muscles and the change in CSA of the trunk in response to an abdominal drawing-in task . These measures of muscle size and function were performed using magnetic resonance imaging . Availability of players for competition games was used to assess the effect of the intervention on the occurrence of injuries . The motor control program involved performance of voluntary contractions of the multifidus and transversus abdominis muscles while receiving feedback from ultrasound imaging . Because all players were to receive the intervention , the trial was delivered as a stepped-wedge design with three treatment arms ( a 15-wk intervention , a 8-wk intervention , and a waitlist control who received a 7-wk intervention toward the end of the playing season ) . Players participated in a Pilates program when they were not receiving the intervention . RESULTS The intervention program was associated with an increase in multifidus muscle size relative to results in the control group . The program was also associated with an improved ability to draw-in the abdominal wall . Intervention was commensurate with an increase in availability for games and a high level of perceived benefit . CONCLUSIONS The motor control program delivered to elite footballers was effective , with demonstrated changes in the size and control of the targeted muscles . In this study , footballers who received the intervention early in the season missed fewer games because of injury than those who received it late in the playing season |
1,229 | 23,832,787 | None showed benefit to ACR regarding OS , yet there was a trend in favor of anthracyclines for disease control .
ACR improved disease control , as measured by PFS and RD with an increased risk for side effects , notably cardiotoxicity . | BACKGROUND Anthracycline-containing regimens ( ACR ) are the most prevalent regimens in the management of patients with advanced follicular lymphoma ( FL ) .
However , there is no proof that they are superior to non-anthracycline-containing regimens ( non-ACR ) .
OBJECTIVES To compare the efficacy of ACRs to other chemotherapy regimens , in the treatment of FL . | BACKGROUND Interferon alfa and cytotoxic drugs have synergistic effects in patients with non-Hodgkin 's lymphoma . In 1986 , we design ed a clinical trial to evaluate the benefit of concomitant administration of recombinant interferon alfa with a regimen containing doxorubicin in patients with follicular non-Hodgkin 's lymphoma . METHODS The trial involved 242 patients with advanced low- grade follicular non-Hodgkin 's lymphoma selected on the basis of clinical , radiographic , and biologic criteria . All patients were treated with a regimen consisting of cyclophosphamide , doxorubicin , teniposide , and prednisone ( CHVP ) , given monthly for six cycles and then every two months for one year . After r and omization , 123 patients also received interferon alfa-2b at a dosage of 5 million units three times weekly for 18 months . The remaining 119 patients received chemotherapy alone . RESULTS As compared with the patients treated with CHVP only , the patients treated with CHVP plus interferon alfa had a higher overall rate of response ( 85 percent vs. 69 percent , P = 0.006 ) , a longer median event-free survival ( 34 months vs. 19 months , P < 0.001 ) , and a higher rate of survival at 3 years ( 86 percent vs. 69 percent , P = 0.02 ) . Granulocyte toxicity was greater in the patients treated with CHVP plus interferon alfa than in those treated with CHVP alone . There were no treatment-related deaths . Interferon alfa had to be stopped because of toxic effects ( fatigue and hepatitis ) in 13 patients ( 11 percent ) . CONCLUSIONS The addition of interferon alfa to a regimen containing doxorubicin increased the rate of response , event-free survival , and overall survival in patients with advanced follicular non-Hodgkin 's lymphoma , without serious toxicity , although some patients were unable to tolerate the side effects A total of 296 evaluable patients with unfavorable categories of malignant lymphoma were r and omly assigned treatment with cyclophosphamide , vincristine , and prednisone plus BCNU ( BCOP ) or doxorubicin ( CHOP ) . In diffuse histiocytic ( DH ) lymphoma , CHOP produced superior complete ( 54 % v 34 % ) and total ( 70 % v 46 % ) response rates . Among the responders to either therapy , no differences were seen in duration of response or survival times . Median duration of response has not been reached with follow-up in excess of 50 months . In categories of lymphoma other than DH ( including small-cell , mixed , and nodular histiocytic lymphomas ) , complete ( 27 % v 29 % ) and total ( 48 % v 54 % ) responses were similar for BCOP and CHOP , as were duration s of response and survival . These data suggest that BCOP and CHOP are equivalent regimens for other categories of malignant lymphomas . CHOP appears preferable for diffuse large-cell categories , since it result ed in greater overall survival in patients with DH lymphoma ; this was due to a significantly greater response rate , since patients with DH lymphoma who did respond to BCOP maintained their response and survived as long as did the CHOP responders PURPOSE The aim of the F2 study was to verify whether a prospect i ve collection of data would enable the development of a more accurate prognostic index for follicular lymphoma ( FL ) by using parameters which could not be retrospectively studied before , and by choosing progression-free survival ( PFS ) as principal end point . PATIENTS AND METHODS Between January 2003 and May 2005 , 1,093 patients with a newly diagnosed FL were registered and 942 individuals receiving antilymphoma therapy were selected as the study population . The variables we used for score definition were selected by means of bootstrap resampling procedures on 832 patients with complete data . Procedures to select the model that would minimize errors were also performed . RESULTS After a median follow-up of 38 months , 261 events for PFS evaluation were recorded . beta2-microglobulin higher than the upper limit of normal , longest diameter of the largest involved node longer than 6 cm , bone marrow involvement , hemoglobin level lower than 12 g/dL , and age older than 60 years were factors independently predictive for PFS . Using these variables , a prognostic model was devised to identify three groups at different levels of risk . The 3-year PFS rate was 91 % , 69 % , and 51 % for patients at low , intermediate , and high risk , respectively ( log-rank = 64.6 ; P < .00001 ) . The 3-year survival rate was 99 % , 96 % , and 84 % for patients at low , intermediate , and high risk , respectively ( P < .0001 ) . CONCLUSION Follicular Lymphoma International Prognostic Index 2 is a simple prognostic index based on easily available clinical data and may represent a promising new tool for the identification of patients with FL at different risk in the era of immunochemotherapy Between July 1 , 1971 and December 31 , 1978 , 150 patients with favorable subtypes of non-Hodgkin 's lymphoma [ nodular poorly differentiated lymphocytic ( NLPD ) , nodular mixed , or diffuse well differentiated lymphocytic ] were entered into prospect i ve r and omized clinical trials at Stanford University . Treatments included involved field , total lymphoid , or whole body irradiation , single alkylating agent chemotherapy , combination chemotherapy with cyclophosphamide , vincristine and prednisone ( CVP ) or with cyclophosphamide , vincristine , procarbazine , and prednisone ( C-MOPP ) , or various combinations of chemotherapy and irradiation . The initial complete response rate ( CR ) was 79 % . Among patients who achieved a CR , 31 % later relapsed . There were 78 patients who either failed to achieve a CR or achieved a CR and later relapsed . Histologic conversion ( change from initially favorable to an unfavorable subtype of non-Hodgkin 's lymphoma ) was documented in 22/78 patients ( 28 % ) . However , the actuarial risk for conversion was actually much greater ( 60 % at 8 yr ) . The median time to documentation of conversion was 51 mo . The most common type of histologic conversion was from NLPD to diffuse histiocytic lymphoma . Documented histologic conversion was often associated with a more aggressive clinical behavior of the lymphoma , and the median survival after conversion was less than 1 yr . However , those patients who achieved a CR after conversion had a more favorable outcome ( actuarial survival 75 % at 5 yr ) . No specific risk factors predictive of histologic conversion could be identified One hundred patients with untreated non-Hodgkin 's lymphoma were entered in a prospect i ve r and omized study in South and West Wales design ed to assess the value of the anthracycline antibiotic , epirubicin ( 4'-epidoxorubicin ) , in their management . Patients with low grade histology and progressive disease were r and omized to receive either epirubicin , vincristine and prednisolone ( EVP ) or cyclophosphamide , vincristine and prednisolone ( CVP ) . The response rate of 81 % in patients receiving EVP with complete remission rate of 52 % were similar to a response rate of 88 % and complete remission rate of 58 % for patients receiving CVP . No difference was observed in survival between the two groups . Patients with high grade lymphoma were r and omized to receive either cyclophosphamide , doxorubicin , vincristine and prednisolone ( CHOP ) or cyclophosphamide , epirubicin , vincristine and prednisolone ( CEOP ) . The response rate was 71 % for CHOP and 84 % for CEOP . The complete remission rates were 46 % for CHOP and 61 % for CEOP . The cardiotoxicity of the two anthracyclines were monitored closely in 45 patients using measurements of systolic time intervals . Patients receiving epirubicin tolerated higher dose per course and higher total cumulative dose with less evidence of compromised left ventricular function than patients receiving doxorubicin . Epirubicin is an effective agent when used in combination chemotherapy in both low grade and high grade lymphoma with less toxicity than doxorubicin PURPOSE Advanced-stage follicular lymphoma is considered incurable . The pace of improvements in treatment has been slow . This article analyzes five sequential cohorts of patients with stage IV follicular lymphoma treated between 1972 and 2002 . METHODS Five consecutive studies ( two were r and omized trials ) involving 580 patients were analyzed for overall survival ( OS ) , failure-free survival ( FFS ) , and survival after first relapse . A proportional hazards analysis , and subset analyses using the follicular lymphoma international prognostic index ( FLIPI ) score were performed . Treatment regimens included : cyclophosphamide , doxorubicin , vincristine , prednisone , bleomycin ( CHOP-Bleo ) ; CHOP-Bleo followed by interferon alfa ( IFN-alpha ) ; a rotation of three regimens ( alternating triple therapy ) , followed by IFN-alpha ; fludarabine , mitoxantrone , dexamethasone ( FND ) followed by IFN-alpha ; and FND plus delayed versus concurrent rituximab followed by IFN-alpha . RESULTS Improvements in 5-year OS ( from 64 % to 95 % ) and FFS ( from 29 % to 60 % ) indicate steady progress , perhaps partly due to more effective salvage therapies , but the FFS data also indicate improved front-line therapies ; these observations held true after controlling for differences in prognostic factors among the cohorts . The FLIPI model adds rigor to and facilitates comparisons among the different cohorts . An unexpected finding in this study was a trend toward an apparent FFS plateau . CONCLUSION Evolving therapy , including the incorporation of biologic agents , has led to stepwise significant outcome improvements for patients with advanced-stage follicular lymphoma . The apparent plateau in the FFS curve , starting approximately 8 to 10 years from the beginning of treatment , raises the issue of the potential curability of these patients The recognition of several new types of non-Hodgkin 's lymphoma ( NHL ) in recent years has led to proposals for changing lymphoma classifications , including a new proposal put forth by the International Lymphoma Study Group ( ILSG ) . However , the clinical significance of the new entities and the practical utility of this new proposal have not been studied . Therefore , we performed a clinical evaluation of the ILSG classification . A cohort of 1,403 cases of NHL was organized at nine study sites around the world and consisted of consecutive patients seen between 1988 and 1990 who were previously untreated . A detailed protocol for histologic and clinical analysis was followed at each site , and immunologic characterization as to T- or B-cell phenotype was required . Five expert hematopathologists visited the sites and each classified each case using the ILSG classification . A consensus diagnosis was also reached in each case , and each expert re review ed a 20 % r and om sample of the cases . Clinical correlations and survival analyses were then performed . A diagnosis of NHL was confirmed in 1,378 ( 98.2 % ) of the cases . The most common lymphoma types were diffuse large B-cell lymphoma ( 31 % ) and follicular lymphoma ( 22 % ) , whereas the new entities comprised 21 % of the cases . Diagnostic accuracy was at least 85 % for most of the major lymphoma types , and reproducibility of the diagnosis was 85 % . Immunophenotyping improved the diagnostic accuracy by 10 % to 45 % for a number of the major types . The clinical features of the new entities were distinctive . Both the histologic types and the patient characteristics as defined by the International Prognostic Index predicted for patient survival . In conclusion we found that the ILSG classification can be readily applied and identifies clinical ly distinctive types of NHL . However , for clinical application , prognostic factors as defined by the International Prognostic Index must be combined with the histologic diagnosis for appropriate clinical decisions Background . In a prospect i ve r and omized manner , this study evaluated the effect of adjuvant chemotherapy ( cyclophosphamide , doxorubicin , vincristine , and prednisone ; CHOP ) in patients with Stage I non‐Hodgkin lymphoma ( NHL ) who have achieved a complete response ( CR ) after radiation therapy ( RT ) PURPOSE Although rituximab ( R ) is commonly used for patients with advanced follicular lymphoma ( FL ) requiring treatment , the optimal associated chemotherapy regimen has yet to be clarified . PATIENTS AND METHODS We conducted an open-label , multicenter , r and omized trial among adult patients with previously untreated stages II to IV FL to compare efficacy of eight doses of R associated with eight cycles of cyclophosphamide , vincristine , and prednisone ( CVP ) or six cycles of cyclophosphamide , doxorubicin , vincristine , and prednisone ( CHOP ) or six cycles of fludarabine and mitoxantrone ( FM ) . The principal end point of the study was time to treatment failure ( TTF ) . RESULTS There were 534 patients enrolled onto the study . Overall response rates were 88 % , 93 % , and 91 % for R-CVP , R-CHOP , and R-FM , respectively ( P=.247 ) . After a median follow-up of 34 months , 3-year TTFs were 46 % , 62 % , and 59 % for the respective treatment groups ( R-CHOP v R-CVP , P=.003 ; R-FM v R-CVP , P=.006 ; R-FM v R-CHOP , P=.763 ) . Three-year progression-free survival ( PFS ) rates were 52 % , 68 % , and 63 % ( overall P=.011 ) , respectively , and 3-year overall survival was 95 % for the whole series . R-FM result ed in higher rates of grade 3 to 4 neutropenia ( 64 % ) compared with R-CVP ( 28 % ) and R-CHOP ( 50 % ; P < .001 ) . Overall , 23 second malignancies were registered during follow-up : four in R-CVP , five in R-CHOP , and 14 in R-FM . CONCLUSION In this study , R-CHOP and R-FM were superior to R-CVP in terms of 3-year TTF and PFS . In addition , R-CHOP had a better risk-benefit ratio compared with R-FM A grading system ( grade s 1–3 ) for follicular lymphoma ( FL ) is used in the WHO classification for lymphoid malignancies based on the absolute number of centroblasts in the neoplastic follicles . Grade 3 FL is further subdivided into 3a and 3b depending on the presence or absence of centrocytes . A total of 231 patients with FL , referred from 1970 to 2001 , were identified from our prospect ively maintained data base . Original diagnostic material s were available for review on 215 patients and these were reclassified according to the WHO grading system . Follicular lymphoma grade s 1 , 2 and 3 accounted for 92 , 68 and 55 patients , respectively . No significant overall survival ( OS ) differences were observed among FL grade s 1–3 ( log rank P=0.25 ) or between grade s 3a and 3b ( log rank P=0.20 ) . No significant failure-free survival ( FFS ) differences were observed among FL grade s 1–3 ( log rank P=0.72 ) or between grade s 3a and 3b ( log rank P=0.11 ) . First-line anthracyclines did not influence OS or FFS ( log rank P=0.86 , P=0.58 , respectively ) in patients with FL grade 3 . There are long-term survivors among patients with FL grade 3 with a continuing risk of relapse . Anthracyclines did not appear to influence survival or disease relapses when given as front-line therapy in our series . The role of anthracyclines should be further evaluated in large r and omised studies PURPOSE This study was undertaken to compare the molecular response ( MR ) rates of 2 regimens , central lymphatic irradiation ( CLI ) and alternating triple therapy ( ATT ) , in the treatment of Stage I-III follicular lymphoma . MR was defined as disappearance of t(14;18 ) ( q32;q21 ) amplified by polymerase chain reaction ( PCR ) . PATIENTS AND METHODS Sixty-five patients with Stage I to III follicular lymphoma were r and omized . CLI consisted of the mantle , abdomen , and pelvic radiation fields . ATT alternated among CHOD-Bleo , ESHAP , and NOPP for 12 courses . Bone marrow ( BM ) and peripheral blood ( PB ) sample s were obtained before treatment for PCR analysis . PCR-positive patients were followed by PCR analysis . The r and om-effects logistic model was fitted to the data from the posttreatment PCRs . The factors included in the model were treatment arm , type of PCR ( BM vs. PB ) , and time to PCR sample procurement from the date of registration . RESULTS At a median follow-up of 71 months , the 5-year relapse-free survival ( RFS ) rates were 45 % and 54 % for CLI and ATT , respectively ( p = 0.42 ) . The probability of attaining an MR increased with time after registration ( p = 0.007 ) , was lower for BM compared with PB ( p = 0.012 ) , and was higher for ATT than for CLI ( p = 0.020 ) . CONCLUSION ATT regimen achieved a higher MR than CLI , although both arms had similar 5-year RFS Pixantrone dimaleate ( pixantrone ) has been shown to have antitumor activity in leukemia and lymphoma in vitro models and to lack delayed cardiotoxicity associated with mitoxantrone in animal models . FND‐R , a combination regimen of fludarabine , mitoxantrone , dexamethasone , and rituximab , has been shown to be an effective regimen for low‐ grade lymphomas PURPOSE To compare mantle-cell lymphomas ( MCLs ) and follicle-center lymphomas ( FCLs ) for their features of clinical presentation , response to chemotherapy , and prognosis on the basis of a prospect i ve r and omized clinical trial . PATIENTS AND METHODS Patients with MCL and FCL who entered onto the prospect i ve r and omized comparison of cyclophosphamide , vincristine , and prednisone ( COP ) versus prednimustine and mitoxantrone ( PmM ) followed by a second r and omization for interferon ( IFN ) maintenance versus observation only . RESULTS One hundred sixty-five of 234 patients had FCL and 45 of 234 patients had MCL . With FCL , both sexes were equally affected ( men , 47 % ) ; patients with MCL were predominantly men ( 78 % ; P < .0004 ) and had a higher median age ( 64 v 53 years ; P < .0001 ) . Patients with MCL also had more widespread disease , reflected by the proportion of patients with two or greater extranodal manifestations ( 43 % v 21 % ; P < .005 ) and nine or greater involved nodal areas ( 64 % v 45 % ; nonsignificant [ NS ] ) . Response to chemotherapy was significantly lower in patients with MCL ( complete remission [ CR ] + partial remission [ PR ] , 69 % v 88 % ; P < .05 ) and occurred at a slower pace . Patients with MCL also had a shorter event-free interval ( median , 8 v 24 months ; P < .0001 ) and overall survival ( median , 28 v 77 months ; P < .0001 ) . In both subtypes , however , patients with less than two residual lymphoma manifestations in remission experienced a relatively good prognosis with an estimated 5-year survival of greater than 60 % for MCL and greater than 75 % for FCL . CONCLUSION MCL and FCL differ substantially in their features of presentation , response to chemotherapy , and long-term prognosis . The extent of residual disease after completion of chemotherapy discriminates patients with different prognosis and may be used for the stratification of postremission strategies PURPOSE Promising new therapeutic options for follicular lymphoma ( FL ) include fludarabine plus mitoxantrone ( FM ) and the mouse/human anti-CD20 antibody , rituximab . We performed a r and omized comparative trial of FM with cyclophosphamide , doxorubicin , vincristine , and prednisone ( CHOP ) front-line chemotherapy with and without sequential rituximab . PATIENTS AND METHODS All previously untreated CD20(+ ) FL patients presenting in 15 Italian cooperative institutions from October 1999 were r and omly allocated to FM or CHOP . Following clinical or molecular restaging , patients in complete remission ( CR ) with bcl-2/IgH negativity ( CR(- ) ) received no further treatment ; those in CR with bcl-2/IgH positivity ( CR(+ ) ) received rituximab , as did those in partial remission ( PR ) with bcl-2/IgH negativity ( PR(- ) ) or positivity ( PR(+ ) ) ; nonresponders ( NR subgroup ) were off study . RESULTS After chemotherapy , the FM arm achieved higher rates of CR ( 68 % [ 49 of 72 patients ] v 42 % [ 29 of 68 patients ] ; P = .003 ) and CR(- ) ( 39 % [ 28 of 72 patients ] v 13 of 68 patients [ 19 % ] ; P = .001 ) . Rituximab elicited CR(- ) in 55 of 95 treated patients ( 58 % ) . The final CR(- ) rate was higher in the FM arm ( 71 % [ 51 of 72 patients ] v 51 % [ 35 of 68 patients ] ; P = .01 ) . However , with a median follow-up of 19 months ( range , 9 to 37 months ) , no statistically significant difference was found among the various study arms in terms of both progression-free ( PFS ) and overall survival ( OS ) . CONCLUSION These results indicate that FM is superior to CHOP for front-line treatment of FL and that rituximab is an effective sequential treatment option . However , they also confirm that this superiority is unlikely to translate into either better PFS or OS Within a multicentre observation study on non-Hodgkin lymphomas ( NHL ) diagnosed according to the Kiel classification advanced stages III and IV of centrocytic ( CC ) lymphoma exhibited the worst prognosis among lymphomas of low- grade malignancy with a 5-year survival probability of less than 10 per cent . Treatment had been solely expectative and palliative with treatment results showing a prognostic superiority of patients achieving partial and complete remissions over non-responders . Therefore , a r and omized multicentre study was initiated to compare the remission-inducing potential of the COP regimen ( Bagley et al. , 1972 ) with that of the more intensive adriamycin-containing CHOP regimen ( McKelvey et al. , 1976 ) . From 91 newly diagnosed CC lymphomas 63 fulfilled r and omization criteria with 37 patients assigned to the COP regimen and 26 patients to the CHOP regimen . Between the COP- and CHOP-treated patients no significant differences could be demonstrated with respect to initial clinical parameters , rate of complete ( 41 per cent versus 58 per cent ) or partial remissions ( 43 per cent versus 31 per cent ) , median overall survival probability ( 32 versus 37 months ) , relapse-free survival ( 10 versus 7 months ) and rates of relapse ( 73 per cent versus 67 per cent ) and death ( 57 per cent versus 50 per cent ) . It can be concluded that CC lymphoma is a typical lymphoma of low- grade malignancy with its inability to reach stable remissions while the demonstration of identical survival probabilities for patients with complete and partial remissions constitutes a unique feature of this lymphoma entity . These observations prove advanced CC lymphoma to represent an incurable neoplastic disease under conventional therapeutic approaches Ninety-nine previously untreated patients with stage III and IV malignant lymphoma were r and omized to receive either cyclic combination chemotherapy ( 50 patients ) or extensive " systemic " radiotherapy ( 49 patients ) . Histologic classification included nodular poorly differentiated lymphoma ( 54 patients ) , nodular mixed lymphoma ( 21 patients ) , and diffuse poorly differentiated lymphoma ( 24 patients ) . High overall response rates were seen with either approach ( 90 % for radiotherpy ; 86 % for chemotherapy ) and complete remission were relatively common ( 60%--80 % ) . Overall median survival of all patients in this trial will exceed 5 years regardless of the induction therapy used ; however , disease-free survival is not commonly achieved with either regimen . Relapse-free survival rates at 4-year followup , regardless of induction regimen , are 13 % for diffuse lymphomas and 24 % for nodular lymphomas . The second prospect i ve trial attempts to use a combined approach and compares cyclic combination chemotherapy with total-body irradiation and combination chemotherapy . Initial results on 34 patients indicate high overall response rates ( 100 % ) and similar complete remission rates ( 64%--67 % ) . With 14 months ' median followup no patients in either arm of the trial have died but relatively equal numbers have relapsed Treatment of disseminated low grade non-Hodgkin 's lymphomas ( NHL ) remains unsolved . Despite an initial high remission rate ( 50%-70 % ) with chemotherapy , relapses occur and only 20 to 40 % of patients are expected to be free of disease after 10 years . From 1981 to 1984 , 113 low grade NHL were studied in order to determine factors influencing survival without progression . In a r and omized trial , patients received either PCOP combination or PACOP for 6 months followed by chlorambucil or CVP for 12 months . Histological distribution was : follicular small cleaved cells 70 patients , follicular mixed 31 patients , small cells CLL type 12 patients . Stage distribution was : stage IV 88 patients with 74 bone marrow involvement , stage III 17 patients , stage II with bulky masses 8 patients . Complete response ( CR ) was observed in 49 patients at the end of treatment . Among the ten variables studied , only stage and the number of sites involved had a significant effect on the probability of achieving CR . Only CR significantly affected the freedom from progression ( P less than 0.01 ) . Median survival after progression was 21 months . Recently , alpha recombinant interferon has been proposed as treatment for low grade NHL . Cumulative results from the literature give a response rate of 42 % on 139 patients . The response rate was higher in follicular NHL than in the CLL type , and response did not clearly correlate with dose . The CR rate was low ( less than 20 % ) and relapses occurred after stopping therapy . Combined use of interferon and chemotherapy is proposed for future clinical trials PURPOSE To evaluate the benefit of anthracycline-based chemotherapy , identify prognostic factors , and determine the value of the International Prognostic Factors Index for patients with follicular large-cell ( FLC ) lymphoma . PATIENTS AND METHODS This retrospective study includes 96 patients with FLC lymphoma treated at Stanford University Medical Center between 1969 and 1991 . Fifty-five patients received doxorubicin plus cyclophosphamide-containing chemotherapy regimens , 21 patients received other chemotherapy regimens , 15 patients received radiotherapy only , and five patients received no initial therapy . Thirty-four patients had stage I or II disease and 62 patients had stage III or IV disease . RESULTS With a median follow-up duration of 5.2 years ( range , 1 to 18 ) , the actuarial 5- and 10-year overall survival rates were 75 % and 54 % , with actuarial 5- and 10-year freedom from progression ( FFP ) rates of 53 % and 42 % , respectively . Patients treated with chemotherapy regimens that contained both doxorubicin and cyclophosphamide had a superior actuarial 10-year FFP rate ( 55 % v 25 % , P = .06 ) and overall survival rate ( 65 % v 42 % , P = .04 ) compared with patients treated with other chemotherapy regimens . Only one patient treated with doxorubicin plus cyclophosphamide relapsed after 3 years . In the multivariate analysis , discordant lymphoma and treatment with chemotherapy regimens not containing both cyclophosphamide and doxorubicin predicted for worse FFP and overall survival rates . In addition , poor performance status and increasing areas of diffuse histology predicted for a worse survival , while anemia and male sex predicted for a worse FFP . The age-specific International Index was useful in predicting outcome ; however , few patients with FLC lymphoma had high-risk features . CONCLUSION The plateau in FFP implies that patients with FLC lymphoma enjoy sustained remissions after st and ard anthracycline-based chemotherapy . FLC lymphoma should continue to be approached as an intermediate- grade lymphoma with curative intent The results obtained with intensive chemotherapy and intensive chemotherapy plus radiotherapy in non-Hodgkin 's lymphomata are reported . A quintuple drug regimen ( mechloretamine , adriamycin , bleomycin , vincristine and prednisone ) in histiocytic lymphomata ( Stage III and IV ) yielded complete remissions in 53 % and complete plus partial remissions in 77 % . These figures were 44 % and 64 % respectively in lymphocytic lymphoma . In Stage III complete responders after combination chemotherapy were subsequently irradiated ( involved field irradiation ) . The median duration of complete remission after completion of radiotherapy was 9 - 5 months in histiocytic and 12 - 0 months in lymphocytic lymphomata . At 2 years actuarial survival in Stage III and IV was better in patients with the lymphocytic type and with nodular pattern than with histiocytic and diffuse patterns . A more recent trial compares , in Stage IV patients , cyclophosphamide , vincristine and prednisone ( CVP ) versus adriamycin , bleomycin and prednisone ( ABP ) . Although the number of evaluable patients is still limited , there appears to be no difference in the response rate between CVP and ABP . In Stages I and II , 6 cycles of CVP were given as adjuvant treatment after radiotherapy . At the present moment , there is no statistical difference in the relapse rate between the group of patients treated with radiotherapy alone and that with radiotherapy plus CVP BACKGROUND Rituximab plus chemotherapy , most often CHOP ( cyclophosphamide , doxorubicin , vincristine , and prednisone ) , is the first-line st and ard of care for patients with advanced indolent lymphoma , and for elderly patients with mantle-cell lymphoma . Bendamustine plus rituximab is effective for relapsed or refractory disease . We compared bendamustine plus rituximab with CHOP plus rituximab ( R-CHOP ) as first-line treatment for patients with indolent and mantle-cell lymphomas . METHODS We did a prospect i ve , multicentre , r and omised , open-label , non-inferiority trial at 81 centres in Germany between Sept 1 , 2003 , and Aug 31 , 2008 . Patients aged 18 years or older with a WHO performance status of 2 or less were eligible if they had newly diagnosed stage III or IV indolent or mantle-cell lymphoma . Patients were stratified by histological lymphoma subtype , then r and omly assigned according to a prespecified r and omisation list to receive either intravenous bendamustine ( 90 mg/m(2 ) on days 1 and 2 of a 4-week cycle ) or CHOP ( cycles every 3 weeks of cyclophosphamide 750 mg/m(2 ) , doxorubicin 50 mg/m(2 ) , and vincristine 1.4 mg/m(2 ) on day 1 , and prednisone 100 mg/day for 5 days ) for a maximum of six cycles . Patients in both groups received rituximab 375 mg/m(2 ) on day 1 of each cycle . Patients and treating physicians were not masked to treatment allocation . The primary endpoint was progression-free survival , with a non-inferiority margin of 10 % . Analysis was per protocol . This study is registered with Clinical Trials.gov , number NCT00991211 , and the Federal Institute for Drugs and Medical Devices of Germany , BfArM 4021335 . FINDINGS 274 patients were assigned to bendamustine plus rituximab ( 261 assessed ) and 275 to R-CHOP ( 253 assessed ) . At median follow-up of 45 months ( IQR 25 - 57 ) , median progression-free survival was significantly longer in the bendamustine plus rituximab group than in the R-CHOP group ( 69.5 months [ 26.1 to not yet reached ] vs 31.2 months [ 15.2 - 65.7 ] ; hazard ratio 0.58 , 95 % CI 0.44 - 0.74 ; p<0.0001 ) . Bendamustine plus rituximab was better tolerated than R-CHOP , with lower rates of alopecia ( 0 patients vs 245 ( 100 % ) of 245 patients who recieved ≥3 cycles ; p<0.0001 ) , haematological toxicity ( 77 [ 30 % ] vs 173 [ 68 % ] ; p<0.0001 ) , infections ( 96 [ 37 % ] vs 127 [ 50 % ] ) ; p=0.0025 ) , peripheral neuropathy ( 18 [ 7 % ] vs 73 [ 29 % ] ; p<0.0001 ) , and stomatitis ( 16 [ 6 % ] vs 47 [ 19 % ] ; p<0.0001 ) . Erythematous skin reactions were more common in patients in the bendamustine plus rituximab group than in those in the R-CHOP group ( 42 [ 16 % ] vs 23 [ 9 % ] ; p=0.024 ) . INTERPRETATION In patients with previously untreated indolent lymphoma , bendamustine plus rituximab can be considered as a preferred first-line treatment approach to R-CHOP because of increased progression-free survival and fewer toxic effects . FUNDING Roche Pharma AG , Ribosepharm/Mundipharma PURPOSE The array of options for the initial management of follicular small cleaved lymphoma ( FSCL ) and follicular mixed lymphoma ( FML ) ranges from little or no therapy to the use of intensive combinations of drugs . The Cancer and Leukemia Group B ( CALGB ) compared two contrasting approaches : a single agent , and combination chemotherapy capable of curing diffuse aggressive lymphomas . PATIENTS AND METHODS A total of 228 patients with stage III or IV FSCL or FML were r and omized to cyclophosphamide or the combination of cyclophosphamide , doxorubicin , vincristine , prednisone , and bleomycin ( CHOP-B ) . Treatment was continued in responders for 2 years beyond maximal response . The primary end point was survival in the most common subtype , FSCL . RESULTS Ninety-one percent of all patients responded ; complete responses were seen in 66 % of those treated with cyclophosphamide and in 60 % treated with CHOP-B ( P = .36 ) . At 10 years with either cyclophosphamide or CHOP-B , respectively , overall time to failure ( 25 % failure free v 33 % ; P = .107 ) and survival ( 44 % alive v 46 % ; P = .79 ) were similar by treatment . Outcomes in FSCL also were similar . In 46 patients with FML , at 10 years the combination was associated with better failure-free ( 9 % v 48 % ; P = .005 ) and overall ( 25 % v 61 % ; P = .024 ) survival . Acute toxic effects were more common with combination chemotherapy . Second malignancies , which might be attributed to treatment , were seen with both approaches . CONCLUSION There is no advantage to the initial use of the relatively intensive combination , CHOP-B , for patients with FSCL compared with the less toxic single agent , cyclophosphamide . However , in an unplanned subgroup analysis , patients with FML who received the combination experienced improved disease control and survival BACKGROUND Fludarabine was associated with a good response and was well tolerated in patients with follicular lymphoma in phase II trials and this treatment may be associated with less adverse events than treatment with CHVP plus interferon in elderly patients . PATIENTS AND METHODS One hundred thirty-one patients older than 59 years with a follicular lymphoma and poor prognosis were r and omized between the association of CHVP ( 12 cycles in 18 months ) plus interferon ( 5 MU TIW for 18 months ) or fludarabine alone ( 25 mg/m2/d x 5 days for 6 cycles , then 20 mg/m2/day for 6 further cycles for 18 months ) . Poor prognosis was defined by the presence of a large tumor mass , poor performance status , the presence of B symptoms , above normal LDH level , or > or = 3 mg/l beta-microglobulin level . RESULTS Patients treated with CHVP plus interferon had a higher response to treatment , a longer time to progression and a longer survival than those treated with fludarabine alone ( P < 0.05 for all analyses ) . With a median follow-up of 29 months , the 2-year failure-free survival was 63 % for the CHVP-plus-interferon arm compared to 49 % for the fludarabine arm and the two-year survival was 77 % and 62 % , respectively . This benefit was confirmed in a multivariate analysis including initial prognostic parameters . Fludarabine alone was associated with less neutropenia than CHVP plus interferon . Interferon was decreased or stopped in 39 % of the patients because of severe fatigue . CONCLUSIONS CHVP plus interferon over 18 months was associated with a better outcome , even though the combination of interferon plus chemotherapy was less well tolerated than fludarabine This study investigated 72 patients ( 12.4 % ) with follicular lymphoma among 582 patients with non-Hodgkin 's lymphoma admitted to our department . Treatment achieved complete remission ( CR ) in 83.3 % of the follicular lymphoma patients , with an overall 5-year survival rate of 63.7 % . The 5-year survival rate was 76.9 % for the 60 patients who achieved CR , and this rate was significantly higher than that for patients who achieved only partial remission ( PR ) ( p < 0.01 ) . The 5-year survival rate was 40 % with the CHOP regimen and 74.3 % with the COP-BLAM regimen . The 3-year survival rate for biweekly COP-BLAM was 88.4 % . The 5-year disease free survival rate for patients who achieved CR was 80.5 % . The rate reached a plateau after 42 months , and the same survival was maintained for more than 10 years . These results suggest that intensive chemotherapy is effective even against follicular lymphoma . The 5-year survival rate for patients who achieved PR , suggesting the importance of the response to initial chemotherapy PURPOSE A first comparative trial of fludarabine ( FLU ) alone versus FLU plus idarubicin ( FLU-ID ) for indolent or mantle-cell lymphomas . PATIENTS AND METHODS From September 1995 to July 1998 , 199 patients aged 25 to 65 years ( median , 54 years ) with newly diagnosed stages II to IV indolent or mantle-cell lymphomas ( st and ard risk according to the International Prognostic Index ) were enrolled onto a multicenter , 1:1 r and omized study . Of the 199 patients who were able to be assessed , 101 were assigned to the FLU group ( six monthly cycles of FLU 25 mg/m(2)/d on days 1 through 5 ) and 98 to the FLU-ID group ( six monthly cycles of FLU 25 mg/m(2)/d on days 1 through 3 and idarubicin 12 mg/m(2 ) on day 1 ) . RESULTS In the FLU group , complete response ( CR ) and partial response rates were 47 % and 37 % , respectively , whereas in the FLU-ID group , they were 39 % and 42 % , respectively . In-depth analysis of the CR rate with respect to histologic type showed that FLU seemed to be superior to FLU-ID in treating follicular lymphomas ( 60 % v 40 % , respectively ) , whereas FLU-ID seemed to be more effective than FLU in treating nonfollicular lymphomas ( small lymphocytic , 43 % v 29 % , respectively ; immunocytoma , 38 % v 23 % , respectively ; P = not significant ) , excluding the mantle-cell subset ( in which there was no difference between the two groups ) . No striking differences were observed between the two protocol s in terms of overall response or toxicity , which was generally mild . However , with a median follow-up of 19 months , only 29 patients ( 62 % ) who received FLU alone have maintained their initial CR , compared with 32 ( 84 % ) of those who received FLU-ID therapy ( P = .021 ) . CONCLUSION Although the FLU-ID regimen may not significantly improve the induction of CR in most indolent-lymphoma patients , our preliminary data do suggest that , with respect to FLU alone , it may be capable of conferring a longer-lasting CR and that it might be superior in terms of CR rate in small lymphocytic and immunocytoma subtypes Two hundred fifty-nine previously untreated patients with low- grade non-Hodgkin 's lymphomas ( NHLs ) , Ann Arbor stages III and IV , entered a r and omized multicenter trial comparing the therapeutic effect of chlorambucil/prednisone ( ChP ) vs. CHOP . All patients had symptomatic disease . The therapeutic aim was to achieve an asymptomatic state in the ChP group ( n = 132 ) , while in CHOP-treated patients ( n = 127 ) the intention was to reach a complete remission ( CR ) . The response rate ( CR+PR at 8 months ) was 36 % in the ChP and 60 % in the CHOP group ( p < 0.01 ) . Three and 5-year survival rates were 59 % and 41 % in the ChP group and 64 % and 44 % in the CHOP group . The corresponding median survival times were 46 and 52 months . After correction for intercurrent deaths , the overall 5-year survival was 49 % for ChP and 54 % for CHOP-treated patients . The differences were statistically not significant . The time from diagnosis to r and omization ( time with asymptomatic disease ) was longer than one year in half of the patients . The median survival time from diagnosis was 68 months , with no differences between the treatment groups . In all histological subgroups ( CLL , IC , CC , and CB-CC ) , a higher remission rate was seen with the CHOP regimen but with no statistically significant influence on survival . Comparing patients below and above 65 years of age , no significant difference in survival was noted between the two treatment groups . The results do not support the use of intensive chemotherapy as first-line therapy in symptomatic low- grade NHL Sixty-six untreated patients with advanced non-Hodgkin 's lymphoma of favourable histological type were allocated alternately to initial treatment with cyclophosphamide , vincristine , and prednisolone or with chlorambucil . The complete remission rate was higher in the group receiving combination chemotherapy , but the overall response rate was the same for both groups . The mean duration of complete remission was the same as that of good partial remission , and was the same for both treatments . The duration of remission was influenced by histological type and extent of disease at presentation , but not age . Those who responded to the initial treatment ( whether with complete or with good partial remission ) survived significantly longer than did non-responders . It is concluded that neither treatment is satisfactory and that new treatment programmes are needed for patients with a favourable prognosis , especially young patients with extensive disease From 1981 to 1984 a r and omized clinical trial was conducted to evaluate the role of doxorubicin in low grade malignancy non-Hodgkin 's lymphoma ( NHL ) . One hundred and thirteen patients were treated by an induction regimen including cyclophosphamide 400 mg/m2 day 1 and 8 , vincristine 1.4 mg/m2 day 1 and 8 , procarbazine 80 mg/m2 day 1 to 14 , prednisone 60 mg/m2 day 1 to 5 ( PCOP regimen ) r and omly associated to doxorubicin : 20 mg/m2 day 1 and 8 ( PACOP regimen ) . Maintenance therapy consisted of 12 monthly courses of chlorambucil 10 mg/m2 for 5 days or association of cyclophosphamide 300 mg/m2 for 3 days , vincristine 1.4 mg/m2 day 1 and prednisone 60 mg/m2 for 5 days . Complete response ( CR ) was obtained in 51 patients ( 45 per cent ) , in 30 patients after induction regimen and in 21 patients after maintenance therapy , without difference according to regimens . Bone marrow involvement ( p = 0.02 ) and number of involved nodal sites ( p = 0.001 ) were found to influence probability of achieving CR . The median time to progression was estimated to 39 months without difference between regimens . Median overall survival is not reached with a median follow-up of 53 months . Multivariate regression analysis permits observation of negative influence on survival of three parameters : initial bone marrow involvement , age over 50 years and incomplete response to treatment . The initial adjunction of doxorubicin did not seem to influence the appearance of histologic progression PURPOSE We review ed survival data of patients with low- grade lymphoma entered on Southwest Oncology Group ( SWOG ) lymphoma trials in 1972 to 1983 to determine the utility of doxorubicin-containing therapy ( cyclophosphamide , doxorubicin , vincristine , and prednisone [ CHOP ] ) in such patients . PATIENTS AND METHODS We identified all patients with low- grade lymphoma , no prior therapy , and stage III or IV disease who were treated with full-dose CHOP induction therapy on any arm of SWOG studies 7204 , 7426 , or 7713 . Survival data for this group of patients were correlated with pretreatment prognostic factors , including histology , patient age , sex , symptom status , performance status , bone marrow or extranodal involvement , and the number of disease sites . The effect of maintenance treatment was also assessed . RESULTS Four hundred fifteen patients met criteria for inclusion in the study group . With median follow-up periods of 12.8 years ( maximum , 19.8 years ) , the median survival duration was 6.9 years . Survival was significantly shorter in patients with follicular mixed or small lymphocytic histology , age greater than 40 years , male sex , B-symptom status , and SWOG performance status greater than 1 . Multivariate regression analysis showed histology , age , and sex to be independent predictors of survival . There was no definite survival plateau of cured patients in any subgroup , although the survival curve for follicular mixed histology patients showed long-term survival of approximately 25 % . Maintenance therapy did not prolong survival . CONCLUSION Doxorubicin-containing treatment did not prolong the overall median survival of low- grade lymphoma patients compared with results with less-aggressive programs 7578 Background : BBR 2778 is a novel aza-anthracenedione that shows structural similarities to the anthracyclines , demonstrates single agent activity in patients with NHL , and does not exhibit cardiotoxic effects in animal models . This phase III open-label study was design ed to compare the efficacy and tolerability of combination rituximab and BBR 2778 , with that of single agent rituximab , in patients ( pts ) with relapsed or refractory indolent NHL . METHODS Pts were r and omly assigned to receive both rituximab and BBR 2778 ( experimental arm ) , or rituximab alone ( control arm ) . In the experimental arm , pts received 375 mg/m2 rituximab IV on days 1 and 8 of cycles 1 and 2 only , and 90 mg/m2 BBR 2778 IV on days 2 and 8 of cycle 1 , and on days 1 and 8 of all subsequent cycles . Pts could receive six 21-day cycles of BBR 2778 . In the control arm , pts received 375 mg/m2 rituximab IV on days 1 , 8 and 15 of cycle 1 and day 1 of cycle 2 only . Disease response was assessed every other cycle according to International Workshop to St and ardize Response Criteria for NHL . Toxicities were assessed throughout the study using NCI-CTC criteria . Study was closed early due to poor enrollment . RESULTS 38 pts ( 20 experimental , 18 control ) were enrolled . Mean age was 66 and 59 years in the experimental and control arm , respectively . Most patients were males and most had ECOG performance status 0 or 1 . Efficacy is summarized in the table . Response rate ( 75 vs 33 % ) and time to progression ( 13.2 vs 8.1 months ) were better in the BBR 2778 arm . Only pts in the experimental arm had study drug related serious adverse events ( 2 febrile neutropenia , 1 pneumonia , 1 neutropenia ) and adverse events result ing in withdrawal ( 6 vs 0 ) . CONCLUSIONS Combination of BBR 2778 and rituximab is superior to rituximab alone with regard to time to progression and overall response rate . BBR 2778 combined with rituximab appeared to be a generally well tolerated regimen in patients with relapsed/refractory indolent NHL . [ Table : see text ] [ Table : see text ] The treatment of Non-Hodgkin 's lymphomas with follicular growth pattern and advanced stage of disease remains controversial . Treatments varying from no initial treatment up to aggressive combination chemotherapy have been advocated . The EORTC Lymphoma Cooperative Group has performed a r and omized prospect i ve trial comparing short duration low dose total body irradiation ( TBI ) vs combination chemotherapy ( CHVmP ) + consolidation radiotherapy . Ninety-three patients were entered ; of 84 evaluable patients , 44 received TBI and 40 CHVmP. Complete remission ( CR ) rates were 36%--TBI and 55%--CHVmP , but overall response rates were identical , 76 versus 69 % . No significant difference in freedom from progression or survival was observed . No unexpected toxicity was seen . Although numbers are small , we can not conclude that aggressive combination chemo-radiotherapy result ed in a better survival . Our analysis confirms that there is a constant risk of relapse . Other approaches should be explored if survival benefit is the ultimate goal in treatment of this patient population PURPOSE To evaluate the feasibility and efficacy of rituximab with short- duration chemotherapy in the first-line treatment of patients with follicular non-Hodgkin 's lymphoma ( NHL ) . PATIENTS AND METHODS Patients with previously untreated stage II-IV follicular NHL , grade 1 or 2 , were eligible for this multicenter phase II trial . All patients received four weekly doses of rituximab ( 375 mg/m(2 ) intravenous ) , followed by three courses of combination chemotherapy ( either cyclophosphamide , doxorubicin , vincristine , and prednisone [ CHOP ] , or cyclophosphamide , vincristine , and prednisone [ CVP ] ) plus rituximab . Patients were evaluated for response after completing treatment , and were then followed up at 3-month intervals . RESULTS Between January 2000 and July 2001 , 86 patients were treated . Eight-two patients ( 95 % ) completed treatment ; no patient was withdrawn due to toxicity . The overall response rate was 93 % , with 55 % complete responses . After a median follow-up of 42 months , the 3- and 4-year actuarial progression-free survivals were 71 % and 62 % , respectively . Five patients ( 6 % ) died from lymphoma ; the overall actuarial survival at 3 years was 95 % . Grade 3/4 leukopenia occurred in 53 % of patients , but only six patients ( 7 % ) had neutropenia or fever . Grade 3/4 nonhematologic toxicities were uncommon . CONCLUSION Rituximab plus short-course chemotherapy is well tolerated as first-line treatment for patients with follicular NHL . The overall and complete response rates are similar to those reported with chemotherapy/rituximab combinations of longer duration . The actuarial progression-free survival of 62 % at 4 years is encouraging , but further follow-up is necessary . Rituximab plus short-course chemotherapy may prove to be as effective as longer- duration chemotherapy and currently provides an attractive option for first-line treatment of elderly patients and others who tolerate chemotherapy poorly As a part of an ongoing prospect i ve controlled trial , the Southwest Oncology Group compared the results of treatment of advanced non‐Hodgkin 's lymphoma with two CHOP regimens ( cyclophosphamide , adriamycin , vincristine and prednisone with either low‐dose bleomycin or BCG by scarification ) to a COP regimen ( cyclophosphamide , vincristine and prednisone ) with low‐dose bleomycin ( COP‐Bleo ) . The study design emphasized histopathology review and systematic restaging to define complete remission ( CR ) . Confirmed rates of CR for 443 evaluable patients were 59 % for 286 patients receiving the CHOP regimens and 59 % for 157 patients receiving COP‐Bleo . Rates of CR were higher for patients with nodular lymphoma ( 69 % ) compared to those with diffuse lymphoma ( 54 % ) ( p = 0.005 ) . For patients with nodular lymphoma there was no difference in CR rates according to treatment . For patients with diffuse lymphomas the CR rate was higher with the CHOP programs ( 58 % ) than with COP‐Bleo ( 44 % ) ( p = 0.10 ) . Overall duration of CR and survival was significantly longer for patients with nodular lymphoma compared to diffuse lymphoma ( p < 0.01 ) . At this time , remission duration and survival were similar regardless of induction regimen used in patients with nodular lymphoma . However , in patients with diffuse lymphoma , the duration of CR and overall survival were improved by treatment with the CHOP regimens compared to COP‐Bleo ( p = 0.02 ) . Thus , in this controlled study we have demonstrated that initial combination chemotherapy employing the CHOP regimen was a superior remission induction therapy for patients with diffuse lymphoma . Cancer 43:417–425 , 1979 Between 1974 and 1977 , 652 patients with non‐Hodgkin 's lymphoma without prior chemotherapy were r and omized to 1 of 3 combination chemotherapy programs design ed to induce complete remission ( CR ) : COP‐bleomycin ( 180 patients ) , CHOP‐bleomycin ( 232 patients ) or CHOP plus immunotherapy with Bacillus Calmette Guerin ( BCG ) ( 240 patients ) . With mature follow‐up , the major effect of BCG immunotherapy was observed in patients with large cell lymphomas ( diffuse or nodular “ histiocytic ” ) and not in other common lymphoma subtypes . CR rate for 65 patients with large cell lymphoma treated with CHOP‐BCG was 68 % compared to 48 % in 61 patients treated with CHOP‐bleomycin ( P = 0.02 ) ( two‐tailed test ) or 44 % for 45 patients treated with COP‐bleomycin ( P = 0.02 ) . CR duration for both CHOP‐based regimens was similar and superior to that produced by COP‐bleomycin ( P = 0.03 ) . Survival of patients with large cell lymphoma treated with CHOP‐BCG was better than that observed with CHOP‐bleomycin ( P = 0.02 ) or COP‐Bleomycin ( P = 0.002 ) . Although the explanation for the favorable effect of BCG remains unclear , further clinical trials to evaluate the combination of chemotherapy and other “ biologic response modifiers ” is warranted for patients with lymphoma Between January 1973 and January 1979 , 131 patients with malignant non‐Hodgkin 's lymphomas ( 107 lymphocytic lymphomas , 24 histiocytic lymphomas ) were treated with cyclophosphamide‐vincristinprednisone ( CVP ) either alone or combined with Adriamycin ( CVP‐A ) . Stage I and II lymphocytic lymphomas were all treated by CVP combined with radiotherapy . The survival curve for this group of patients plateaued at 89 % from the 12th to the 60th month , which was the endpoint of the study . For Stage III and IV nodular lymphocytic lymphomas , actuarial survival was 69 % at five years in the CVP‐treated group as compared to 54 % at three years in the group treated with CVP‐A. For Stage III and IV diffuse lymphocytic lymphomas , the complete response rate and median survival were respectively 25 % and 24 months in patients treated with CVP , as compared to 67 % ( P < 0.01 ) and 26 months in the group treated with CVP‐A. For histiocytic lymphomas , the complete response rate was 50 % in the CVP‐treated group as compared to 83 % in the group treated with CVP‐A. Most remarkable was the fact that while in the CVP treated group median survival was only 17 months , the small group of patients treated with CVP‐A exhibited considerably improved survival with a horizontal survival curve at 90 % after 36 months ( 12 patients ) . These results show that the CVP protocol remains an excellent treatment for nodular lymphocytic lymphomas . The addition of Adriamycin ( CVP‐A ) as well as its inclusion in other drugs combination , has raised hopes for remissions of long duration and even for cures in patients with histiocytic lymphomas . Finally , in diffuse lymphocytic lymphomas , efforts will have to be pursued to improve the prognosis which remains poor despite the increased complete response rate achieved by the addition of Adriamycin BACKGROUND AND OBJECTIVES We report the activity of two combinations of fludarabine ( FLU ) , one with cyclophosphamide ( FLU/CY ) and the second with CY plus mitoxantrone ( FLU/CY/MITO ) . The aim of the study was to evaluate the activity and toxicity of these two schedules in patients with non-Hodgkin 's lymphoma ( NHL ) . DESIGN AND METHODS Twenty-two patients with recurrent low grade non-Hodgkin 's lymphoma ( LGL ) received FLU/CY ( FLU 25 mg/m(2 ) days 1 to 3 , CY 300 mg/m(2 ) days 1 to 3 ) , and 31 patients received FLU/CY/MITO ( FLU 25 mg/m(2 ) days 1 to 3 , CY 300 mg/m(2 ) days 1 to 3 , mitoxantrone 10 mg/m(2 ) day 1 ) . Patients received antibiotic oral prophylaxis during all treatments and growth factors ( G-CSF ) when grade III granulocytopenia ( WHO scale ) occurred . RESULTS Of the 53 patients , 31 achieved complete remission ( CR ) ( 58 % ) and 16 partial remission ( PR ) ( 30 % ) . Response was similar in both arms of the study . After 3 courses , 77 % of patients who achieved CR showed a complete disappearance of disease . Seventy-nine per cent of patients experienced granulocytopenia . Few patients had fever , all without infection . One patient died with fever of unknown origin three months after completion of six courses of treatment . INTERPRETATION AND CONCLUSIONS Both treatments were seen to be effective in recurrent low- grade NHL . Antibiotic prophylaxis with G-CSF support seems to reduce treatment-related infection Results of an EORTC trial ( 20751 ) in non-Hodgkin lymphomas are presented . Patients were treated in the same way independent of the histological type . There were 468 patients in the study of whom 124 patients were in stage I ( 85 % 5 year survival ) , 57 in stage II ( 55 % ) , 121 in stage III ( 55 % ) and 166 in stage IV ( 45 % ) . Using the Kiel classification the low grade lymphomas were subdivided into two categories : those with a follicular ( 80 % 5 year survival ) and with a diffuse cell pattern ( 50 % 5 year survival ) with an intermediate prognosis compared with the high grade lymphomas ( 35 % 5 year survival ) . Treatment was stratified according to stage . In stage I regional radiotherapy was given followed by r and omization for maintenance chemotherapy with Vincristine , Cyclophosphamide and Prednisone . No influence in survival was seen ( 85 % at 5 years ) , although disease free survival was better in the maintenance chemotherapy group ( 75 % vs 55 % at 5 years ) . In stage II regional radiotherapy was followed , after r and omization , by transdiaphragmatic irradiation , all patients received maintenance chemotherapy . The group was too small to draw conclusions about the effect of this treatment . Primary radiotherapy in stage II disease with diffuse histology gave bad results . Patients in stage III and IV were treated with 8 courses of chemotherapy with Adriamycin , VM26 , Cyclophosphamide and Prednisone , given in two different time schedules . Iceberg radiation was then given to areas with initially large or slowly responding disease . All patients had maintenance chemotherapy . No difference was found for the 2 chemotherapy schedules in remission rate , disease free interval and survival . In stage III and IV patients with a follicular lymphoma have a longer relapse free interval and total survival ( 39 % and 68 % at 5 years ) compared with those with a lymphoma diffuse histology ( 19 and 30 % at 5 years ) . Patients with stage IV disease due to bone marrow involvement only had a better prognosis compared with stage IV disease for other reasons The current study was initiated to compare the anti-lymphoma activity and side-effects of prednimustine/mitoxantrone ( PmM ) vs cyclophosphamide , vincristine , prednisone ( COP ) in patients with advanced low- grade non-Hodgkin 's lymphomas in way of a prospect i ve r and omized multicenter trial . Two hundred and forty-six patients with stage III or IV centroblastic-centrocytic ( CB-CC ( Kiel-classification ) ) or follicle center lymphoma ( FCL ( REAL classification ) ) and centrocytic ( CC ) or mantle-cell-lymphoma ( MCL ) were r and omized for therapy with either PmM or COP and are fully evaluable for response and toxicity . PmM consisted of prednimustine 100 mg/m2/day on days 1 - 5 and mitoxantrone 8 mg/m2 /day days 1 and 2 , while COP comprised cyclophosphamide 400 mg/m2/day on days 1 - 5 , vincristine 1.4 mg/m2/day on day 1 and prednisone 100 mg/m2/day on days 1 - 5 . Both regimens were repeated for a total of six cycles followed by an additional two courses for consolidation in responding cases and a subsequent second r and omization for interferon alpha maintenance vs observation only . Overall response rates were comparable with 83 % complete and partial remissions after COP and 84 % remissions after PmM. PmM revealed a significantly higher rate of complete remissions ( 36 vs 18 % , P < 0.006 ) , the majority being achieved after four courses . The more rapid and possibly also more effective reduction of the lymphoma cell mass by PmM result ed in a tendency to a longer event-free interval for patients achieving remissions after PmM as compared to COP with estimated median event-free intervals of 31 vs 14 months , respectively ( P=0.04 ) . Separate analysis of lymphoma subtypes showed a tendency to a lower rate of complete remission in CC or MCL as compared to CB-CC or FCL ( 16 vs 30 % , P=0.12 , NS ) while overall response rates were in a similar range ( 81 vs 85 % ) . In both subtypes , PmM induced a higher rate of complete remission while overall response rates were comparable after PmM or COP . Treatment associated side-effects comprised predominantly myelosuppression and granulocytopenia in particular which was more frequently observed after PmM than COP ( 43 vs 31 % , P < 0.0001 ) . This difference was clinical ly irrelevant , however , since serious infectious complications were encountered in less than 3 % of cycles after both regimens . COP therapy was associated with a significantly higher incidence and degree of hair loss and complete alopecia ( 31 vs 2 % ) as well as of peripheral neurotoxicity ( 23 vs 2 % ) . These data show that both PmM and COP reveal a high anti-lymphoma activity in patients with advanced stage non-Hodgkin 's lymphoma . PmM appears advantageous with a higher rate of complete remissions and a better tolerability with regard to secondary side-effects . A longer follow-up is needed to assess the long-term effects of initial treatment on disease-free and overall survival and the impact on additional maintenance therapy with interferon alpha BACKGROUND Patients with follicular lymphoma can have long survival times , but disease progression typically occurs 3 - 5 years after initial treatment . We assessed the potential benefit of 2 years of rituximab maintenance after first-line treatment in patients with follicular lymphoma receiving a rituximab plus chemotherapy regimen . METHODS The r and omised , open-label PRIMA study was undertaken in 223 centres in 25 countries . 1217 patients with previously untreated follicular lymphoma needing systemic therapy received one of three non-r and omised immunochemotherapy induction regimens used in routine practice . 1019 patients achieving a complete or partial response were then r and omly assigned to receive 2 years of rituximab maintenance therapy ( 375 mg/m(2 ) every 8 weeks ) or observation . Treatment was assigned equally by central ised block r and omisation , stratified by induction regimen , response , region , and centre . Neither the participants nor those giving the interventions , assessing outcomes , and analysing data were masked to group assignments . The primary endpoint was progression-free survival ( PFS ) . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00140582 . FINDINGS 505 patients were assigned to rituximab maintenance and 513 to observation ( one patient died during r and omisation ) . With a median follow-up of 36 months ( IQR 30 - 42 ) , PFS was 74·9 % ( 95 % CI 70·9 - 78·9 ) in the rituximab maintenance group ( 130 patients progressed ) and 57·6 % ( 53·2 - 62·0 ) in the observation group ( 218 progressed ; hazard ratio [ HR ] 0·55 , 95 % CI 0·44 - 0·68 , p<0·0001 ) . 2 years after r and omisation , 361 patients ( 71·5 % ) in the rituximab maintenance group were in complete or unconfirmed complete response versus 268 ( 52·2 % ) in the observation group ( p=0·0001 ) . Overall survival did not differ significantly between groups ( HR 0·87 , 95 % CI 0·51 - 1·47 ) . Grade 3 and 4 adverse events were recorded in 121 patients ( 24 % ) in the rituximab maintenance group and 84 ( 17 % ) in the observation group ( risk ratio 1·46 , 95 % CI 1·14 - 1·87 ; p=0·0026 ) . Infections ( grade s 2 - 4 ) were the most common adverse event , occurring in 197 ( 39 % ) and 123 ( 24 % ) patients , respectively ( risk ratio 1·62 , 95 % CI 1·35 - 1·96 ; p<0·0001 ) . INTERPRETATION 2 years of rituximab maintenance therapy after immunochemotherapy as first-line treatment for follicular lymphoma significantly improves PFS . FUNDING Groupe d'Etude des Lymphomes de l'Adulte ( GELA ) and F Hoffmann-La Roche PURPOSE Optimal therapy of follicular lymphoma ( FL ) is not defined . We analyzed a large prospect i ve cohort study to identify current demographics and patterns of care of FL in the United States . PATIENTS AND METHODS The National LymphoCare Study is a multicenter , longitudinal , observational study design ed to collect information on treatment regimens and outcomes for patients with newly diagnosed FL in the United States . Patients were enrolled between 2004 and 2007 . There is no study -specific prescribed treatment regimen or intervention . RESULTS Two thous and seven hundred twenty-eight subjects were enrolled at 265 sites , including the 80 % of patients enrolled from nonacademic sites . Using the Follicular Lymphoma International Prognostic Index ( FLIPI ) , three distinct groups independent of histologic grade could be defined . Initial therapeutic strategy was : observation , 17.7 % ; rituximab monotherapy , 13.9 % ; clinical trial 6.1 % ; radiation therapy , 5.6 % ; chemotherapy only , 3.2 % ; chemotherapy plus rituximab , 51.9 % . Chemotherapy plus rituximab regimens were : rituximab plus cyclophosphamide , doxorubicin , vincristine , prednisone , 55.0 % ; rituximab plus cyclophosphamide , vincristine , and prednisone , 23.1 % ; rituximab plus fludarabine based , 15.5 % ; other , 6.4 % . The choice to initiate therapy rather than observe was associated with age , FLIPI , stage , and grade ( P < .01 ) . Significant differences in treatment ( P < .01 ) across regions of the United States were noted . Contrary to practice guidelines , treatment of stage I FL frequently omits radiation therapy . CONCLUSION Widely disparate therapeutic approaches are utilized for FL . Initial therapy is deferred in a small subset of patients . There is no single st and ard of care for the treatment of de novo FL , although antibody use is ubiquitous when therapy is initiated . These disparate approaches to the initial care of patients with FL render a heterogeneous group of patients at relapse |
1,230 | 31,142,516 | Similarly , vision gain was not significantly different between cn-AMD patients treated with aflibercept versus ranibizumab .
Rates of systemic serious harms were similar across anti-VEGF agents .
Intravitreal bevacizumab was a reasonable alternative to ranibizumab and aflibercept in patients with cn-AMD , DMO , RVO-MO and m-CNV .
The only exception was for patients with DME and low visual acuity ( < 69 early treatment diabetic retinopathy study [ ETDRS ] letters ) , where treatment with aflibercept was associated with significantly higher vision gain ( ≥15 ETDRS letters ) than bevacizumab or ranibizumab at 12 months ; but the significant effects were not maintained at 24 months . | OBJECTIVES To evaluate the comparative effectiveness and safety of intravitreal bevacizumab , ranibizumab and aflibercept for patients with choroidal neovascular age-related macular degeneration ( cn-AMD ) , diabetic macular oedema ( DMO ) , macular oedema due to retinal vein occlusion ( RVO-MO ) and myopic choroidal neovascularisation ( m-CNV ) . | Purpose The purpose of this study was to compare the efficacy of intravitreal aflibercept and ranibizumab in the treatment of diabetic macular edema ( DME ) in eyes with moderate visual loss . Patients and methods This study is a r and omized prospect i ve study . Seventy eyes with DME were divided into two groups ( each containing 35 eyes ) . Eyes in group I were treated with intravitreal injection of 2 mg/0.05 mL aflibercept and eyes in group II were treated with intravitreal injection of 0.5 mg/0.1 mL ranibizumab . All the eyes had three successive injections as a loading dose ( with 1 month interval ) , and then the patients were followed up monthly for 12 months . The outcomes of the study were visual acuity , central macular thickness ( CMT ) , and the number of re-injections of the drug . Results Mean age of the patients in group I was 55.05±4.7 years and in group II was 56.64±5.8 years ( P=0.17 ) . The mean baseline best corrected visual acuity ( BCVA ) of eyes treated with aflibercept was 0.17±0.05 and with ranibizumab was 0.18±0.04 ( P=0.9 ) . BCVA was improved in both the groups at the end of the follow-up period and was found to be 0.42±0.28 and 0.37±0.23 , respectively ( P=0.27 ) . The mean baseline CMT of eyes in group I was 465.29±33.7 µm and in group II was 471.5±34.4 µm ( P=0.65 ) . CMT decreased in both the groups to 360.8±85.7 µm and 387.3±87.8 µm , respectively ( P=0.2 ) . The mean number of drug re-injection was 2.62±0.68 and 3.03±0.95 in both the groups , respectively ( P=0.02 ) . Conclusion Aflibercept and ranibizumab have the same efficacy in the treatment of DME in eyes with moderate visual loss but with less number of drug re-injection and less treatment burden with aflibercept ( 2.62±0.68 versus 3.03±0.95 ) Purpose To report 1-year visual and anatomic outcomes of a prospect i ve , double-masked r and omised clinical trial comparing bevacizumab with ranibizumab for the treatment of age-related macular degeneration ( AMD ) . Methods Patients who met inclusion criteria were r and omised 2 : 1 to bevacizumab or ranibizumab . All subjects and investigators ( except for the pharmacist responsible for study assignments ) were masked to treatment arms . Visual acuity was taken on Early Treatment Diabetic Retinopathy Study chart . Patients were given either bevacizumab or ranibizumab every month for the first 3 months , followed by an optical coherence tomography-guided , variable-dosing treatment schedule . Main outcomes measured included visual acuity , foveal thickness , and total number of injections over the 1-year treatment period . Results In total , 15 patients received bevacizumab and 7 patients received ranibizumab . The average pre-operative visual acuity was 34.9 letters in the bevacizumab group , and 32.7 letters in the ranibizumab group . At 1-year follow-up , mean vision was 42.5 letters in the bevacizumab group , and 39.0 letters in the ranibizumab group . Two-tailed t-test failed to showed statistical significance between the two groups ( P=0.5 ) . Patients in the bevacizumab group underwent an average of eight injections , whereas patients in the ranibizumab group underwent a mean of four injections ( P=0.001 ) . Conclusion The 1-year outcomes of a prospect i ve , double-masked , r and omised clinical trial comparing bevacizumab with ranibizumab failed to show a difference in visual and anatomic outcomes between the two treatments for choroidal neovascularisation in AMD . Total injections given over the treatment period were significantly different between the two groups . Further studies with larger sample sizes are warranted OBJECTIVE Two similarly design ed , phase-3 studies ( VEGF Trap-Eye : Investigation of Efficacy and Safety in Wet AMD [ VIEW 1 , VIEW 2 ] ) of neovascular age-related macular degeneration ( AMD ) compared monthly and every-2-month dosing of intravitreal aflibercept injection ( VEGF Trap-Eye ; Regeneron , Tarrytown , NY , and Bayer HealthCare , Berlin , Germany ) with monthly ranibizumab . DESIGN Double-masked , multicenter , parallel-group , active-controlled , r and omized trials . PARTICIPANTS Patients ( n = 2419 ) with active , subfoveal , choroidal neovascularization ( CNV ) lesions ( or juxtafoveal lesions with leakage affecting the fovea ) secondary to AMD . INTERVENTION Patients were r and omized to intravitreal aflibercept 0.5 mg monthly ( 0.5q4 ) , 2 mg monthly ( 2q4 ) , 2 mg every 2 months after 3 initial monthly doses ( 2q8 ) , or ranibizumab 0.5 mg monthly ( Rq4 ) . MAIN OUTCOME MEASURES The primary end point was noninferiority ( margin of 10 % ) of the aflibercept regimens to ranibizumab in the proportion of patients maintaining vision at week 52 ( losing < 15 letters on Early Treatment Diabetic Retinopathy Study [ ETDRS ] chart ) . Other key end points included change in best-corrected visual acuity ( BCVA ) and anatomic measures . RESULTS All aflibercept groups were noninferior and clinical ly equivalent to monthly ranibizumab for the primary end point ( the 2q4 , 0.5q4 , and 2q8 regimens were 95.1 % , 95.9 % , and 95.1 % , respectively , for VIEW 1 , and 95.6 % , 96.3 % , and 95.6 % , respectively , for VIEW 2 , whereas monthly ranibizumab was 94.4 % in both studies ) . In a prespecified integrated analysis of the 2 studies , all aflibercept regimens were within 0.5 letters of the reference ranibizumab for mean change in BCVA ; all aflibercept regimens also produced similar improvements in anatomic measures . Ocular and systemic adverse events were similar across treatment groups . CONCLUSIONS Intravitreal aflibercept dosed monthly or every 2 months after 3 initial monthly doses produced similar efficacy and safety outcomes as monthly ranibizumab . These studies demonstrate that aflibercept is an effective treatment for AMD , with the every-2-month regimen offering the potential to reduce the risk from monthly intravitreal injections and the burden of monthly monitoring . FINANCIAL DISCLOSURE(S ) Proprietary or commercial disclosure may be found after the references PURPOSE To compare efficacy and safety of intravitreal aflibercept injection ( IAI ) with macular laser photocoagulation for diabetic macular edema ( DME ) over 3 years . DESIGN Two similarly design ed phase 3 trials : VISTADME and VIVIDDME . PARTICIPANTS Patients ( eyes ; n = 872 ) with central -involved DME . METHODS Eyes received IAI 2 mg every 4 weeks ( 2q4 ) , IAI 2 mg every 8 weeks after 5 monthly doses ( 2q8 ) , or laser control . From week 24 , if rescue treatment criteria were met , IAI patients received active laser , and laser control patients received IAI 2q8 . From week 100 , laser control patients who had not received IAI rescue treatment received IAI as needed per retreatment criteria . MAIN OUTCOME MEASURES The primary end point was the change from baseline in best-corrected visual acuity ( BCVA ) at week 52 . We report the 148-week results . RESULTS Mean BCVA gain from baseline to week 148 with IAI 2q4 , IAI 2q8 , and laser control was 10.4 , 10.5 , and 1.4 letters ( P < 0.0001 ) in VISTA and 10.3 , 11.7 , and 1.6 letters ( P < 0.0001 ) in VIVID , respectively . The proportion of eyes that gained ≥15 letters from baseline at week 148 was 42.9 % , 35.8 % , and 13.6 % ( P < 0.0001 ) in VISTA and 41.2 % , 42.2 % , and 18.9 % ( P < 0.0001 ) in VIVID , respectively . Greater proportions of eyes treated with IAI 2q4 and IAI 2q8 versus those treated with laser control had an improvement of ≥2 steps in the Diabetic Retinopathy Severity Scale ( DRSS ) score in both VISTA ( 29.9 % and 34.4 % vs. 20.1 % [ P = 0.0350 , IAI 2q4 ; P = 0.0052 , IAI 2q8 ] ) and VIVID ( 44.3 % and 47.8 % vs. 17.4 % [ P < 0.0001 for both ] ) . In an integrated safety analysis , the most frequent ocular serious adverse event was cataract ( 3.1 % , 2.1 % , 0.3 % for 2q4 , 2q8 , and control ) . CONCLUSIONS Visual improvements observed with both IAI regimens ( over laser control ) at weeks 52 and 100 were maintained at week 148 , with similar overall efficacy in the IAI 2q4 and IAI 2q8 groups . Treatment with IAI also had positive effects on the DRSS score . Over 148 weeks , the incidence of adverse events was consistent with the known safety profile of IAI PURPOSE To provide 2-year results comparing anti-vascular endothelial growth factor ( VEGF ) agents for center-involved diabetic macular edema ( DME ) using a st and ardized follow-up and retreatment regimen . DESIGN R and omized clinical trial . PARTICIPANTS Six hundred sixty participants with visual acuity ( VA ) impairment from DME . METHODS R and omization to 2.0-mg aflibercept , 1.25-mg repackaged ( compounded ) bevacizumab , or 0.3-mg ranibizumab intravitreous injections performed up to monthly using a protocol -specific follow-up and retreatment regimen . Focal/grid laser photocoagulation was added after 6 months if DME persisted . Visits occurred every 4 weeks during year 1 and were extended up to every 4 months thereafter when VA and macular thickness were stable . MAIN OUTCOME MEASURES Change in VA , adverse events , and retreatment frequency . RESULTS Median numbers of injections were 5 , 6 , and 6 in year 2 and 15 , 16 , and 15 over 2 years in the aflibercept , bevacizumab , and ranibizumab groups , respectively ( global P = 0.08 ) . Focal/grid laser photocoagulation was administered in 41 % , 64 % , and 52 % , respectively ( aflibercept vs. bevacizumab , P < 0.001 ; aflibercept vs. ranibizumab , P = 0.04 ; bevacizumab vs. ranibizumab , P = 0.01 ) . At 2 years , mean VA improved by 12.8 , 10.0 , and 12.3 letters , respectively . Treatment group differences varied by baseline VA ( P = 0.02 for interaction ) . With worse baseline VA ( 20/50 to 20/320 ) , mean improvement was 18.1 , 13.3 , and 16.1 letters , respectively ( aflibercept vs. bevacizumab , P = 0.02 ; aflibercept vs. ranibizumab , P = 0.18 ; ranibizumab vs. bevacizumab , P = 0.18 ) . With better baseline VA ( 20/32 to 20/40 ) , mean improvement was 7.8 , 6.8 , and 8.6 letters , respectively ( P > 0.10 , for pairwise comparisons ) . Anti-Platelet Trialists ' Collaboration ( APTC ) events occurred in 5 % with aflibercept , 8 % with bevacizumab , and 12 % with ranibizumab ( global P = 0.047 ; aflibercept vs. bevacizumab , P = 0.34 ; aflibercept vs. ranibizumab , P = 0.047 ; ranibizumab vs. bevacizumab , P = 0.20 ; global P = 0.09 adjusted for potential confounders ) . CONCLUSIONS All 3 anti-VEGF groups showed VA improvement from baseline to 2 years with a decreased number of injections in year 2 . Visual acuity outcomes were similar for eyes with better baseline VA . Among eyes with worse baseline VA , aflibercept had superior 2-year VA outcomes compared with bevacizumab , but superiority of aflibercept over ranibizumab , noted at 1 year , was no longer identified . Higher APTC event rates with ranibizumab over 2 years warrants continued evaluation in future trials PURPOSE To describe outcomes 5 years after initiating treatment with bevacizumab or ranibizumab for neovascular age-related macular degeneration ( AMD ) . DESIGN Cohort study . PARTICIPANTS Patients enrolled in the Comparison of AMD Treatments Trials . METHODS Patients were assigned r and omly to ranibizumab or bevacizumab and to 1 of 3 dosing regimens . After 2 years , patients were released from the clinical trial protocol . At 5 years , patients were recalled for examination . MAIN OUTCOME MEASURES Visual acuity ( VA ) and morphologic retinal features . RESULTS Visual acuity was obtained for 647 of 914 ( 71 % ) living patients with average follow-up of 5.5 years . The mean number of examinations for AMD care after the clinical trial ended was 25.3 , and the mean number of treatments was 15.4 . Most patients ( 60 % ) were treated 1 time or more with a drug other than their assigned drug . At the 5-year visit , 50 % of eyes had VA of 20/40 or better and 20 % had VA of 20/200 or worse . Mean change in VA was -3 letters from baseline and -11 letters from 2 years . Among 467 eyes with fluorescein angiography , mean total lesion area was 12.9 mm(2 ) , a mean of 4.8 mm(2 ) larger than at 2 years . Geographic atrophy was present in 213 of 515 ( 41 % ) gradable eyes and was subfoveal in 85 eyes ( 17 % ) . Among 555 eyes with spectral-domain optical coherence tomography , 83 % had fluid ( 61 % intraretinal , 38 % subretinal , and 36 % sub-retinal pigment epithelium ) . Mean foveal total thickness was 278 μm , a decrease of 182 μm from baseline and 20 μm from 2 years . The retina was abnormally thin ( < 120 μm ) in 36 % of eyes . Between 2 and 5 years , the group originally assigned to ranibizumab for 2 years lost more VA than the bevacizumab group ( -4 letters ; P = 0.008 ) . Otherwise , there were no statistically significant differences in VA or morphologic outcomes between drug or regimen groups . CONCLUSIONS Vision gains during the first 2 years were not maintained at 5 years . However , 50 % of eyes had VA of 20/40 or better , confirming anti-vascular endothelial growth factor therapy as a major long-term therapeutic advance for neovascular AMD Purpose : To compare intravitreal bevacizumab ( IVB ) and intravitreal ranibizumab ( IVR ) in the treatment of subfoveal choroidal neovascularization associated with pathologic myopia . Methods : Fifty-five patients fulfilling inclusion and exclusion criteria were r and omized either to IVB or to IVR . After the first injection , re-treatments were performed on a pro re nata basis in monthly examinations over an 18-month follow-up . Primary outcome measures were the change in mean best-corrected visual acuity and the proportion of eyes improving in best-corrected visual acuity by > 1 and > 3 lines at the 18-month examination . Results : Forty-eight eyes received the treatment and were subsequently included in the analysis . At the 18-month examination , a significant improvement of 1.7 lines and 1.8 lines compared with baseline were noticed in the IVR and IVB subgroups , respectively . The difference in the final mean best-corrected visual acuity between the groups was not significant . A 3-line gain or higher was noted in 30 % of eyes in the IVR subgroup and 44 % of eyes in the IVB subgroup . Although both groups attained a significant improvement in central macular thickness , the IVR subgroup achieved a faster central macular thickness reduction . A significantly lower number of injections were administered in the IVR subgroup ( 2.5 ) compared with the IVB subgroup ( 4.7 ; P < 0.001 ) . Conclusion : Intravitreal ranibizumab and IVB are effective in the treatment of subfoveal myopic choroidal neovascularization . Intravitreal ranibizumab achieved greater efficacy than IVB in terms of the mean number of injections administered 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 Context : Ranibizumab and bevacizumab are used widely for treating patients with choroidal neovascular membrane ( CNVM ) secondary to age-related macular degeneration ( AMD ) . Aims : To determine and compare the efficacy and safety of intravitreal ranibizumab and bevacizumab in treatment of CNVM due to AMD . Setting s and Design : Prospect i ve comparative case series carried out in an eye institute and eye department of a hospital in Kolkata , India . Material s and Methods : One hundred and four eyes with CNVM due to AMD were r and omized into two groups . Group A ( n=54 ; 24 occult ) received monthly intravitreal ranibizumab injections ( 0.5 mg in 0.05 ml ) and Group B ( n=50 ; 22 occult ) received monthly bevacizumab injections ( 1.25 mg in 0.05 ml ) for 3 consecutive months and then as per study criteria . Data analysis done using SPSS software . P-value of < 0.05 was considered statistically significant . Results : The mean best corrected visual acuity ( BCVA ) in the ranibizumab group increased from 58.19 Early Treatment Diabetic Retinopathy Study ( ETDRS ) letters at baseline to 64 ETDRS letters at month 3 ( P<0.001 ) . In bevacizumab group mean BCVA increased from 56.80 to 61.72 ETDRS letters at month 3 ( P<0.001 ) . At the end of 18 months , there was no statistically significant difference between groups A and B with respect to change in BCVA ( P=0.563 ) or central macular thickness ( CMT ; P=0.281 ) , as measured by optical coherence tomography ( Stratus OCT 3000 ) . No significant sight-threatening complications developed . Conclusions : Ranibizumab and bevacizumab are equally safe and efficacious in treating CNVM due to AMD PURPOSE To compare the efficacy and safety of bevacizumab versus ranibizumab when administered according to a treat- and -extend protocol for the treatment of neovascular age-related macular degeneration ( AMD ) . DESIGN Multicenter , r and omized , noninferiority trial with a noninferiority limit of 5 letters . PARTICIPANTS Patients aged ≥ 50 years with previously untreated neovascular AMD in 1 eye and best-corrected visual acuity ( BCVA ) between 20/25 and 20/320 . METHODS Patients were r and omly assigned to receive ranibizumab 0.5 mg or bevacizumab 1.25 mg intravitreal injections . Monthly injections were given until inactive disease was achieved . The patients were then followed with a gradual extension of treatment interval by 2 weeks at a time up to a maximum of 12 weeks . If signs of recurrent disease appeared , the treatment interval was shortened by 2 weeks at a time . MAIN OUTCOME MEASURES Change in visual acuity at 1 year . RESULTS Between March 2009 and July 2012 , 441 patients were r and omized at 10 ophthalmological centers in Norway . The 1-year visit was completed by 371 patients . In the per protocol analysis at 1 year , bevacizumab was equivalent to ranibizumab , with 7.9 and 8.2 mean letters gained , respectively ( 95 % confidence interval [ CI ] of mean difference , -2.4 to 2.9 ; P = 0.845 ) . The intention-to-treat analysis was concordant . There was no significant difference in measured central retinal thickness ( CRT ) , with a mean decrease of -112 μm for bevacizumab and -120 μm for ranibizumab ( 95 % CI of mean difference , -13 to 28 ; P = 0.460 ) . There was a statistically significant difference ( P = 0.001 ) between the drugs regarding the number of treatments : 8.9 for bevacizumab and 8.0 for ranibizumab . There were fewer arteriothrombotic events in the bevacizumab group ( 1.4 % ) than in the ranibizumab group ( 4.5 % ) ( P = 0.050 ) and significantly more cardiac events in the ranibizumab group ( P = 0.036 ) . However , patients treated with ranibizumab more often had a history of myocardial infa rct ion ( P = 0.021 ) . CONCLUSIONS Bevacizumab and ranibizumab had equivalent effects on visual acuity at 1 year when administered according to a treat- and -extend protocol . The visual acuity results at 1 year were comparable to those of other clinical trials with monthly treatment . The numbers of serious adverse events were small PURPOSE To evaluate the efficacy and safety of intravitreal ranibizumab in diabetic macular edema ( DME ) patients . DESIGN Two parallel , method ologically identical , phase III , multicenter , double-masked , sham injection-controlled , r and omized studies . PARTICIPANTS Adults with vision loss from DME ( best-corrected visual acuity [ BCVA ] , 20/40 - 20/320 Snellen equivalent ) and central subfield thickness ≥275 μm on time-domain optical coherence tomography ( OCT ) . INTERVENTION Monthly intravitreal ranibizumab ( 0.5 or 0.3 mg ) or sham injections . Macular laser was available per- protocol -specified criteria . MAIN OUTCOME MEASURES Proportion of patients gaining ≥15 letters in BCVA from baseline at 24 months . RESULTS In RISE ( NCT00473330 ) , 377 patients were r and omized ( 127 to sham , 125 to 0.3 mg , 125 to 0.5 mg ) . At 24 months , 18.1 % of sham patients gained ≥15 letters versus 44.8 % of 0.3-mg ( P<0.0001 ; difference vs sham adjusted for r and omization stratification factors , 24.3 % ; 95 % confidence interval [ CI ] , 13.8 - 34.8 ) and 39.2 % of 0.5-mg ranibizumab patients ( P<0.001 ; adjusted difference , 20.9 % ; 95 % CI , 10.7 - 31.1 ) . In RIDE ( NCT00473382 ) , 382 patients were r and omized ( 130 to sham , 125 to 0.3 mg , 127 to 0.5 mg ) . Significantly more ranibizumab-treated patients gained ≥15 letters : 12.3 % of sham patients versus 33.6 % of 0.3-mg patients ( P<0.0001 ; adjusted difference , 20.8 % ; 95 % CI , 11.4 - 30.2 ) and 45.7 % of 0.5-mg ranibizumab patients ( P<0.0001 ; adjusted difference , 33.3 % ; 95 % CI , 23.8 - 42.8 ) . Significant improvements in macular edema were noted on OCT , and retinopathy was less likely to worsen and more likely to improve in ranibizumab-treated patients . Ranibizumab-treated patients underwent significantly fewer macular laser procedures ( mean of 1.8 and 1.6 laser procedures over 24 months in the sham groups vs 0.3 - 0.8 in ranibizumab groups ) . Ocular safety was consistent with prior ranibizumab studies ; endophthalmitis occurred in 4 ranibizumab patients . The total incidence of deaths from vascular or unknown causes , nonfatal myocardial infa rct ions , and nonfatal cerebrovascular accidents , which are possible effects from systemic vascular endothelial growth factor inhibition , was 4.9 % to 5.5 % of sham patients and 2.4 % to 8.8 % of ranibizumab patients . CONCLUSIONS Ranibizumab rapidly and sustainably improved vision , reduced the risk of further vision loss , and improved macular edema in patients with DME , with low rates of ocular and nonocular harm BACKGROUND Bevacizumab has been suggested to have similar effectiveness to ranibizumab for treatment of neovascular age-related macular degeneration . The Inhibition of VEGF in Age-related choroidal Neovascularisation ( IVAN ) trial was design ed to compare these drugs and different regimens . Here , we report the findings at the prespecified 2-year timepoint . METHODS In a multicentre , 2 × 2 factorial , non-inferiority r and omised trial , we enrolled adults aged at least 50 years with active , previously untreated neovascular age-related macular degeneration and a best corrected distance visual acuity ( BCVA ) of at least 25 letters from 23 hospitals in the UK . Participants were r and omly assigned ( 1:1:1:1 ) to intravitreal injections of ranibizumab ( 0·5 mg ) or bevacizumab ( 1·25 mg ) in continuous ( every month ) or discontinuous ( as needed ) regimens , with monthly review . Study participants and clinical assessors were masked to drug allocation . Allocation to continuous or discontinuous treatment was masked up to 3 months , at which point investigators and participants were unmasked . The primary outcome was BCVA at 2 years , with a prespecified non-inferiority limit of 3·5 letters . The primary safety outcome was arterial thrombotic event or hospital admission for heart failure . Analyses were by modified intention to treat . This trial is registered , number IS RCT N92166560 . FINDINGS Between March 27 , 2008 , and Oct 15 , 2010 , 628 patients underwent r and omisation . 18 were withdrawn ; 610 received study drugs ( 314 ranibizumab ; 296 bevacizumab ) and were included in analyses . 525 participants reached the visit at 2 years : 134 ranibizumab in continuous regimen , 137 ranibizumab in discontinuous regimen , 127 bevacizumab in continuous regimen , and 127 bevacizumab in discontinuous regimen . For BCVA , bevacizumab was neither non-inferior nor inferior to ranibizumab ( mean difference -1·37 letters , 95 % CI -3·75 to 1·01 ; p=0·26 ) . Discontinuous treatment was neither non-inferior nor inferior to continuous treatment ( -1·63 letters , -4·01 to 0·75 ; p=0·18 ) . Frequency of arterial thrombotic events or hospital admission for heart failure did not differ between groups given ranibizumab ( 20 [ 6 % ] of 314 participants ) and bevacizumab ( 12 [ 4 % ] of 296 ; odds ratio [ OR ] 1·69 , 95 % CI 0·80 - 3·57 ; p=0·16 ) , or those given continuous ( 12 [ 4 % ] of 308 ) and discontinuous treatment ( 20 [ 7 % ] of 302 ; 0·56 , 0·27 - 1·19 ; p=0·13 ) . Mortality was lower with continuous than discontinuous treatment ( OR 0·47 , 95 % CI 0·22 - 1·03 ; p=0·05 ) , but did not differ by drug group ( 0·96 , 0·46 - 2·02 ; p=0·91 ) . INTERPRETATION Ranibizumab and bevacizumab have similar efficacy . Reduction in the frequency of retreatment result ed in a small loss of efficacy irrespective of drug . Safety was worse when treatment was administered discontinuously . These findings highlight that the choice of anti-VEGF treatment strategy is less straightforward than previously thought . FUNDING UK National Institute for Health Research Health Technology Assessment programme Aims The aim was to compare the efficacy of intravitreal therapy with bevacizumab and ranibizumab for choroidal neovascularization ( CNV ) in pathologic myopia ( PM ) . Methods This was a prospect i ve multicenter r and omized nonblinded trial . Results In seven centers , 78 eyes were r and omized 1:1 to treatment with bevacizumab ( group B , 40 eyes ) or ranibizumab ( group R , 38 eyes ) given with an “ on dem and ” regimen ( PRN ) . The mean follow-up was 19 months ( SD 2 , range 12–24 ) . The mean BCVA at baseline was 0.60 logMAR ( 20/80 Snellen equivalent , Seq ) and 50 letter score ( ls ) . Mean final BCVA was 0.51 LogMAR ( 20/63 Seq ) and 57 ls ( p = 0.0009 and p = 0.0002 , respectively ) . In group B , mean basal BCVA was 0.52 logMAR ( 20/63 Seq ) and 54 ls , and final BCVA was 0.51 logMar ( 20/63 Seq ) and 57 ls . In group R , mean basal BCVA was 0.62 logMAR ( 20/80 Seq ) and 45 ls , and the final values were 0.50 logMAR ( 20/63 Seq ) and 58 ls . Statistical comparison of the two groups showed no significant difference ( logMAR p = 0.90 and letters p = 0.78 ) . Multivariate analysis showed no influence of age or previous photodynamic treatment ( PDT ) on final visual changes . The mean number of treatments in the first year was 2.7 in group B and 2.3 in group R ( p = 0.09 ) . Conclusion Myopic CNV equally benefits from on-dem and intravitreal injection of either bevacizumab or ranibizumab ; the therapeutic effect is independent of previous PDT and age Purpose To assess the efficacy and safety of intravitreal bevacizumab ( IVB ) compared with ranibizumab ( IVR ) in the treatment of macular oedema due to branch retinal vein occlusion ( BRVO ) . Methods In this prospect i ve , r and omised , non-inferiority trial , 75 participants with macular oedema due to BRVO received intravitreal injections of ranibizumab or bevacizumab after 1:1 block r and omisation . The primary outcome measure was the difference in mean changes in best-corrected visual acuity ( BCVA ) at 6 months . Secondary outcome measures included mean change in central retinal thickness ( CRT ) , the proportion of patients improving by > 15 letters and the proportion of patients developing neovascularisation . Results Participants received either IVR ( n=37 ) or IVB ( n=38 ) . The mean BCVA at baseline was 52.8±14.4 letters ( 20/80 ) and 56.1±10.0 letters ( 20/80 ) ( p=0.24 ) in the ranibizumab and bevacizumab groups , respectively . At 6 months , the mean gains in BCVA were + 18.1 letters ( p<0.0001 ; 95 % CI , + 12.8 to + 22.6 ) in the ranibizumab group and + 15.6 letters ( p<0.0001 ; 95 % CI + 12.0 to + 20.5 ) in the bevacizumab group . The difference between the mean visual gains of the treated groups ( bevacizumab – ranibizumab ) was −2.5 letters ( 95 % CI −8.0 to + 5.0 ; p=0.74 ) . Mean reductions in CRT at 6 months were 177.1±122.3 µm in the ranibizumab group ( p<0.0001 ) and 201.7±166.2 µm in the bevacizumab group ( p<0.0001 ) , with no significant difference between the two groups ( p=0.48 ) . The mean numbers of ranibizumab and bevacizumab injections were 3.2±1.5 and 3.0±1.4 , respectively ( p=0.55 ) . Two serious adverse events occurred in the ranibizumab group and one in the bevacizumab group but both were unrelated to intravitreal injections . Conclusions This study demonstrated significant gain in visual acuity in eyes with BRVO treated with either bevacizumab or ranibizumab . Pro-re-nata strategy was effective in maintaining the visual gain . Trial registration number http://www.ctri.nic.in/ CTRI/2012/01/003120 Aim To evaluate intravitreal VEGF Trap-Eye ( VTE ) in patients with macular oedema secondary to central retinal vein occlusion ( CRVO ) . Methods In this double-masked study , 177 patients were r and omised ( 3:2 ratio ) to intravitreal injections of VTE 2 mg or sham procedure every 4 weeks for 24 weeks . Best-corrected visual acuity was evaluated using the Early Treatment Diabetic Retinopathy Study chart . Central retinal thickness ( CRT ) was measured with optical coherence tomography . Results From baseline until week 24 , more patients receiving VTE ( 60.2 % ) gained ≥15 letters compared with those receiving sham injections ( 22.1 % ) ( p<0.0001 ) . VTE patients gained a mean of 18.0 letters compared with 3.3 letters with sham injections ( p<0.0001 ) . Mean CRT decreased by 448.6 and 169.3 µm in the VTE and sham groups ( p<0.0001 ) . The most frequent ocular adverse events in the VTE arm were typically associated with the injection procedure or the underlying disease , and included eye pain ( 11.5 % ) , increased intraocular pressure ( 9.6 % ) and conjunctival haemorrhage ( 8.7 % ) . Conclusions VTE 2 mg every 4 weeks was efficacious in CRVO with an acceptable safety profile . Vision gains with VTE were significantly higher than with observation/panretinal photocoagulation if needed . Based on these data , VTE may provide a new treatment option for CRVO Aim The current accepted st and ard treatment for neovascular age-related macular degeneration ( AMD ) consists of antivascular endothelial growth factor agents including ranibizumab and bevacizumab . The aim of the study was to examine whether bevacizumab is inferior to ranibizumab with respect to maintaining/improving visual acuity . Methods In this prospect i ve r and omised parallel group multicentre trial patients aged more than 50 years with treatment naive nAMD were included at 10 Austrian centres . Patients were r and omised to treatment either with 0.5 mg ranibizumab or 1.25 mg bevacizumab . Both groups received three initial monthly injections and thereafter monthly evaluation of visual acuity and the activity of the lesion . Re-treatment was scheduled as needed . Outcome measures were early treatment of diabetic retinopathy visual acuity , retinal thickness , lesion size and safety evaluation . Results A total of 321 patients were recruited of which four had to be excluded due to different reasons . Of the 317 remaining patients 154 were r and omised into the bevacizumab group and 163 into the ranibizumab group . At month 12 , there was a mean increase of early treatment of diabetic retinopathy visual acuity of 4.9 letters in the bevacizumab and 4.1 letters in the ranibizumab group ( p=0.78 ) . Furthermore , there were no significant differences in the decrease of retinal thickness , change of lesion size and number of adverse events between the groups . Conclusions Bevacizumab was equivalent to ranibizumab for visual acuity at all time points over 1 year . There was no significant difference of decrease of retinal thickness or number of adverse events PURPOSE To compare the measurements of visual acuity ( VA ) results measured with Snellen and Early Treatment Diabetic Retinopathy Study ( ETDRS ) charts in eyes with and without age-related macular degeneration ( AMD ) . DESIGN Cross-sectional study . PARTICIPANTS One hundred four participants ( 190 eyes ) selected from a university retina practice ; 80 participants ( 142 eyes ) had some degree of AMD . METHODS Visual acuity was measured in each patient using st and ard procedure with both Snellen and ETDRS charts in r and om order . Statistical analysis of the results was performed . MAIN OUTCOME MEASURES Difference in VA measured by both charts in logarithm of minimal angle of resolution ( logMAR ) notations . RESULTS Overall , the mean Snellen VA was 0.78 logMAR (= 20/120 ) , and the mean ETDRS VA in the same eye was 0.54 logMAR (= 20/70 ; P<0.001 ) . In the low vision group ( < 20/200 ) , represented by patients with AMD , the average difference in number of lines was considerably larger than in the good vision range ( > 20/30 ) . On average , 20/200 on Snellen was 20/95 on ETDRS ( > 3 lines difference ) , and 20/30 on Snellen was 20/25 on ETDRS ( < 1 line difference ) . CONCLUSION Our results show poor agreement between the Snellen and ETDRS charts , and it was more pronounced in the group with poor vision . The ETDRS measurements yielded better VA , particularly in participants with vision < 20/200 ( representing more advanced AMD patients ) . We suggest taking these findings into consideration when comparing outcomes in clinical practice s ( which typically measure VA using st and ard Snellen charts ) with outcomes from clinical trials ( which typically measure VA using ETDRS charts ) OBJECTIVE To test the reliability and validity of the 51-item Field Test Version of the National Eye Institute Visual Function Question naire ( NEI-VFQ ) across 5 common chronic eye conditions . DESIGN Prospect i ve observational cohort study of persons with 1 of 5 chronic eye diseases who were scheduled for nonurgent visits in ophthalmology practice s or had low vision from any cause , and a reference sample of persons without eye disease . SETTING Six university-based ophthalmology practice s and the National Eye Institute Clinical Center , Bethesda , Md. PATIENTS Eligible participants had to have 1 of the following eye conditions : age-related cataracts , age-related macular degeneration , diabetic retinopathy , primary open-angle glaucoma , cytomegalovirus retinitis , or low vision from any cause . Each of the 7 sites also enrolled persons in a reference sample . Reference sample participants had no evidence of underlying eye disease but were scheduled for either screening eye examinations or correction of refractive error . All eligible persons had to be aged 21 years or older , English speaking , and cognitively able to give informed consent and participate in a health status interview . MEASUREMENTS AND MAIN RESULTS To provide the data needed to assess the reliability and validity of the 51-item NEI-VFQ , all subjects completed an interview that consisted of the 51-item NEI-VFQ , the Medical Outcomes Study 36-Item Short-Form Health Survey , and at least 1 measure of vision-targeted functional status . Estimates of internal consistency and test-retest reproducibility indicate that the 51-item NEI-VFQ is reliable . Tests of association with other scales and clinical variables support the construct validity of the survey . CONCLUSIONS In this cross-sectional study , the 51-item NEI-VFQ seems to be reliable and valid and should be a useful tool for group-level comparisons of vision-targeted , health-related quality of life in clinical research . Additionally , the psychometric properties of the NEI-VFQ were not influenced by the type or severity of the underlying eye disease , suggesting that the measure will provide reproducible and valid data when used across multiple eye conditions BACKGROUND Clinical trials have established the efficacy of ranibizumab for the treatment of neovascular age-related macular degeneration ( AMD ) . In addition , bevacizumab is used off-label to treat AMD , despite the absence of similar supporting data . METHODS In a multicenter , single-blind , noninferiority trial , we r and omly assigned 1208 patients with neovascular AMD to receive intravitreal injections of ranibizumab or bevacizumab on either a monthly schedule or as needed with monthly evaluation . The primary outcome was the mean change in visual acuity at 1 year , with a noninferiority limit of 5 letters on the eye chart . RESULTS Bevacizumab administered monthly was equivalent to ranibizumab administered monthly , with 8.0 and 8.5 letters gained , respectively . Bevacizumab administered as needed was equivalent to ranibizumab as needed , with 5.9 and 6.8 letters gained , respectively . Ranibizumab as needed was equivalent to monthly ranibizumab , although the comparison between bevacizumab as needed and monthly bevacizumab was inconclusive . The mean decrease in central retinal thickness was greater in the ranibizumab-monthly group ( 196 μm ) than in the other groups ( 152 to 168 μm , P=0.03 by analysis of variance ) . Rates of death , myocardial infa rct ion , and stroke were similar for patients receiving either bevacizumab or ranibizumab ( P>0.20 ) . The proportion of patients with serious systemic adverse events ( primarily hospitalizations ) was higher with bevacizumab than with ranibizumab ( 24.1 % vs. 19.0 % ; risk ratio , 1.29 ; 95 % confidence interval , 1.01 to 1.66 ) , with excess events broadly distributed in disease categories not identified in previous studies as areas of concern . CONCLUSIONS At 1 year , bevacizumab and ranibizumab had equivalent effects on visual acuity when administered according to the same schedule . Ranibizumab given as needed with monthly evaluation had effects on vision that were equivalent to those of ranibizumab administered monthly . Differences in rates of serious adverse events require further study . ( Funded by the National Eye Institute ; Clinical Trials.gov number , NCT00593450 . ) OBJECTIVE To assess long-term efficacy and safety of intravitreal inserts releasing 0.2 μg/d ( low dose ) or 0.5 μg/d ( high dose ) fluocinolone acetonide ( FAc ) in patients with diabetic macular edema ( DME ) . DESIGN Two r and omized , sham injection-controlled , double-masked , multicenter clinical trials . PARTICIPANTS Subjects with persistent DME despite ≥1 macular laser treatment were r and omized 1:2:2 to sham injection ( n = 185 ) , low-dose insert ( n = 375 ) , or high-dose insert ( n = 393 ) . METHODS Subjects received study drug or sham injection and after 6 weeks were eligible for rescue laser . Based on retreatment criteria , additional study drug or sham injections could be given after 1 year . MAIN OUTCOME MEASURES Percentage of patients with improvement of ≥15 letters from baseline . Secondary outcomes included other parameters of visual function and foveal thickness . RESULTS At month 36 , the percentage of patients who gained ≥15 in letter score using the last observation carried forward method was 28.7 % ( low dose ) and 27.8 % ( high dose ) in the FAc insert groups compared with 18.9 % ( P = 0.018 ) in the sham group , and considering only those patients still in the trial at month 36 , it was 33.0 % ( low dose ) and 31.9 % ( high dose ) compared with 21.4 % in the sham group ( P = 0.030 ) . Preplanned subgroup analysis demonstrated a doubling of benefit compared with sham injections in patients who reported duration of DME ≥3 years at baseline ; the percentage who gained ≥15 in letter score at month 36 was 34.0 % ( low dose ; P<0.001 ) or 28.8 % ( high dose ; P = 0.002 ) compared with 13.4 % ( sham ) . An improvement ≥2 steps in the Early Treatment Diabetic Retinopathy Study retinopathy scale occurred in 13.7 % ( low dose ) and 10.1 % ( high dose ) compared with 8.9 % in the sham group . Almost all phakic patients in the FAc insert groups developed cataract , but their visual benefit after cataract surgery was similar to that in pseudophakic patients . The incidence of incisional glaucoma surgery at month 36 was 4.8 % in the low-dose group and 8.1 % in the high-dose insert group . CONCLUSIONS In patients with DME FAc inserts provide substantial visual benefit for up to 3 years and would provide a valuable addition to the options available for patients with DME Importance Studies have established the efficacy and safety of aflibercept for the treatment of macular edema due to central retinal vein occlusion . Bevacizumab is used off-label to treat this condition despite the absence of supporting data . Objective To investigate whether bevacizumab is noninferior to aflibercept for the treatment of macular edema secondary to central retinal or hemiretinal vein occlusion . Design , Setting , and Participants The SCORE2 r and omized noninferiority clinical trial was conducted at 66 private practice or academic centers in the United States , and included 362 patients with macular edema due to central retinal or hemiretinal vein occlusion who were r and omized 1:1 to receive aflibercept or bevacizumab . The first participant was r and omized on September 17 , 2014 , and the last month 6 visit occurred on May 6 , 2016 . Analyses included data available as of December 30 , 2016 . Interventions Eyes were r and omized to receive intravitreal injection of bevacizumab ( 1.25 mg ; n = 182 ) or aflibercept ( 2.0 mg ; n = 180 ) every 4 weeks through month 6 . Main Outcomes and Measures The primary outcome was mean change in visual acuity ( VA ) letter score ( VALS ) from the r and omization visit to the 6-month follow-up visit , based on the best-corrected electronic Early Treatment Diabetic Retinopathy Study VALS ( scores range from 0 - 100 ; higher scores indicate better VA ) . The noninferiority margin was 5 letters , and statistical testing for noninferiority was based on a 1-sided 97.5 % confidence interval . Results Among 362 r and omized participants ( mean [ SD ] age , 69 [ 12 ] years ; 157 [ 43.4 % ] women ; mean [ SD ] VALS at baseline , 50.3 [ 15.2 ] [ approximate Snellen VA 20/100 ] ) , 348 ( 96.1 % ) completed the month 6 follow-up visit . At month 6 , the mean VALS was 69.3 ( a mean increase from baseline of 18.6 ) in the bevacizumab group and 69.3 ( a mean increase from baseline of 18.9 ) in the aflibercept group ( model-based estimate of between-group difference , −0.14 ; 97.5 % CI , −3.07 to ∞ ; P = .001 for noninferiority ) , meeting criteria for noninferiority . Ocular adverse events in the aflibercept group included 4 participants with intraocular pressure ( IOP ) more than 10 mm Hg greater than baseline ; ocular adverse events in the bevacizumab group included 1 participant with endophthalmitis ( culture negative ) , 9 with IOP more than 10 mm Hg greater than baseline , 2 with IOP higher than 35 mm Hg , and 1 with angle-closure glaucoma not attributed to the study drug or procedure . Conclusions and Relevance Among patients with macular edema due to central retinal or hemiretinal vein occlusion , intravitreal bevacizumab was noninferior to aflibercept with respect to visual acuity after 6 months of treatment OBJECTIVE To assess the efficacy and safety of intravitreal vascular endothelial growth factor ( VEGF ) Trap-Eye in eyes with macular edema secondary to central retinal vein occlusion ( CRVO ) . DESIGN Multicenter , r and omized , prospect i ve , controlled trial . PARTICIPANTS One hundred eighty-nine eyes with macular edema secondary to CRVO . METHODS Eyes were r and omized 3:2 to receive VEGF Trap-Eye 2 mg or sham injection monthly for 6 months . MAIN OUTCOME MEASURES The proportion of eyes with a ≥15-letter gain or more in best-corrected visual acuity ( BCVA ) at week 24 ( primary efficacy end point ) , mean changes in BCVA and central retinal thickness ( CRT ) , and proportion of eyes progressing to neovascularization of the anterior segment , optic disc , or elsewhere in the retina . RESULTS At week 24 , 56.1 % of VEGF Trap-Eye treated eyes gained 15 letters or more from baseline versus 12.3 % of sham-treated eyes ( P<0.001 ) . The VEGF Trap-Eye treated eyes gained a mean of 17.3 letters versus sham-treated eyes , which lost 4.0 letters ( P<0.001 ) . Central retinal thickness decreased by 457.2 μm in eyes treated with VEGF Trap-Eye versus 144.8 μm in sham-treated eyes ( P<0.001 ) , and progression to any neovascularization occurred in 0 and 5 ( 6.8 % ) of eyes treated with VEGF Trap-Eye and sham-treated eyes , respectively ( P = 0.006 ) . Conjunctival hemorrhage , reduced visual acuity , and eye pain were the most common adverse events ( AEs ) . Serious ocular AEs were reported by 3.5 % of VEGF Trap-Eye patients and 13.5 % of sham patients . Incidences of nonocular serious AEs generally were well balanced between both groups . CONCLUSIONS At 24 weeks , monthly intravitreal injection of VEGF Trap-Eye 2 mg in eyes with macular edema result ing from CRVO improved visual acuity and CRT , eliminated progression result ing from neovascularization , and was associated with a low rate of ocular AEs related to treatment PURPOSE To compare the short-term efficacy and safety of intravitreal ranibizumab versus bevacizumab in treating myopic choroidal neovascularization ( CNV ) . DESIGN Prospect i ve , comparative , r and omized , interventional study . METHODS Thirty-two eyes from 32 patients with myopic CNV were consecutively enrolled and r and omly treated , in a 1:1 ratio , with intravitreal ranibizumab ( 0.5 mg ) or bevacizumab ( 1.25 mg ) as needed , after the first injection . ETDRS best-corrected visual acuity ( BCVA ) , foveal center thickness ( FCT ) on optical coherence tomography ( OCT ) , and fluorescein angiographic findings were examined before and after treatment . Patients were followed up for 6 months . RESULTS No statistically significant difference in the BCVA improvement , as well as in the FCT reduction , was found between groups during follow-up ( P value at 1 , 3 , 6 months > .05 ) . Complete resolution of fluorescein leakage was observed in all 16 bevacizumab-treated eyes and in 15 out of 16 ( 93.7 % ) ranibizumab-treated eyes . No ocular or systemic adverse effects from treatment were encountered . CONCLUSION This r and omized clinical study can not determine a statistically significant difference in anti-VEGF treatment effect between ranibizumab and bevacizumab for the treatment of CNV secondary to pathologic myopia . A larger study is required to determine the relative efficacy and duration of action of these drugs PURPOSE To assess the efficacy and safety of intraocular injections of 0.3 mg or 0.5 mg ranibizumab in patients with macular edema after central retinal vein occlusion ( CRVO ) . DESIGN Prospect i ve , r and omized , sham injection-controlled , double-masked , multicenter clinical trial . PARTICIPANTS A total of 392 patients with macular edema after CRVO . METHODS Eligible patients were r and omized 1:1:1 to receive monthly intraocular injections of 0.3 or 0.5 mg of ranibizumab or sham injections . MAIN OUTCOME MEASURES The primary efficacy outcome measure was mean change from baseline best-corrected visual acuity ( BCVA ) letter score at month 6 . Secondary outcomes included other parameters of visual function and central foveal thickness ( CFT ) . RESULTS Mean ( 95 % confidence interval [ CI ] ) change from baseline BCVA letter score at month 6 was 12.7 ( 9.9 - 15.4 ) and 14.9 ( 12.6 - 17.2 ) in the 0.3 mg and 0.5 mg ranibizumab groups , respectively , and 0.8 ( -2.0 to 3.6 ) in the sham group ( P<0.0001 for each ranibizumab group vs. sham ) . The percentage of patients who gained > or = 15 letters in BCVA at month 6 was 46.2 % ( 0.3 mg ) and 47.7 % ( 0.5 mg ) in the ranibizumab groups and 16.9 % in the sham group ( P<0.0001 for each ranibizumab group vs. sham ) . At month 6 , significantly more ranibizumab-treated patients ( 0.3 mg = 43.9 % ; 0.5 mg = 46.9 % ) had BCVA of > or = 20/40 compared with sham patients ( 20.8 % ; P<0.0001 for each ranibizumab group vs. sham ) , and CFT had decreased by a mean of 434 microm ( 0.3 mg ) and 452 microm ( 0.5 mg ) in the ranibizumab groups and 168 microm in the sham group ( P<0.0001 for each ranibizumab group vs. sham ) . The median percent reduction in excess foveal thickness at month 6 was 94.0 % and 97.3 % in the 0.3 mg and 0.5 mg groups , respectively , and 23.9 % in the sham group . The safety profile was consistent with previous phase III ranibizumab trials , and no new safety events were identified in patients with CRVO . CONCLUSIONS Intraocular injections of 0.3 mg or 0.5 mg ranibizumab provided rapid improvement in 6-month visual acuity and macular edema following CRVO , with low rates of ocular and nonocular safety events |
1,231 | 31,549,451 | There is a positive trend of singing interventions reducing pain intensity , but more equivocal support for reductions in pain interference and depression .
Group singing appears to have potential to reduce pain intensity , pain interference and depression ; however , we conclude there is only partial support for singing on some pain outcomes based on the limited available evidence of varied quality .
Group singing may be an effective and safe approach for reducing persistent pain and depression in people with long-term health conditions | BACKGROUND AND OBJECTIVES Singing can have a range of health benefits ; this paper review s evidence of the effects of group singing for chronic pain in people with long-term health conditions . | A growing number of empirical studies have revealed that diaphragmatic breathing may trigger body relaxation responses and benefit both physical and mental health . However , the specific benefits of diaphragmatic breathing on mental health remain largely unknown . The present study aim ed to investigate the effect of diaphragmatic breathing on cognition , affect , and cortisol responses to stress . Forty participants were r and omly assigned to either a breathing intervention group ( BIG ) or a control group ( CG ) . The BIG received intensive training for 20 sessions , implemented over 8 weeks , employing a real-time feedback device , and an average respiratory rate of 4 breaths/min , while the CG did not receive this treatment . All participants completed pre- and post-tests of sustained attention and affect . Additionally , pre-test and post-test salivary cortisol concentrations were determined in both groups . The findings suggested that the BIG showed a significant decrease in negative affect after intervention , compared to baseline . In the diaphragmatic breathing condition , there was a significant interaction effect of group by time on sustained attention , whereby the BIG showed significantly increased sustained attention after training , compared to baseline . There was a significant interaction effect of group and time in the diaphragmatic breathing condition on cortisol levels , whereby the BIG had a significantly lower cortisol level after training , while the CG showed no significant change in cortisol levels . In conclusion , diaphragmatic breathing could improve sustained attention , affect , and cortisol levels . This study provided evidence demonstrating the effect of diaphragmatic breathing , a mind-body practice , on mental function , from a health psychology approach , which has important implication s for health promotion in healthy individuals BACKGROUND Among non-pharmacological therapies , musical intervention is often used for patients with Alzheimer 's disease ( AD ) and patients presenting chronic pain . However , their efficacy is still under debate . OBJECTIVE Our aim was to determine the efficacy of choral singing versus painting sessions on chronic pain , mood , quality of life , and cognition in AD patients . METHODS In this multicenter r and omized controlled trial , 59 mild AD patients were r and omized to a 12-week singing ( SG ; n = 31 ) or painting group ( PG ; n = 28 ) . Chronic pain , anxiety , depression , and quality of life were assessed before , after , and 1 month after the sessions . Cognitive abilities were assessed before and after interventions . The evolution of these different measures was assessed with mixed linear models . The primary data analysis was by intention-to-treat , and completed by a ' per protocol ' approach . RESULTS Both singing and painting interventions led to significant pain reduction ( Time effect : F = 4.71 ; p = 0.01 ) , reduced anxiety ( Time effect : F = 10.74 ; p < 0.0001 ) , improved Quality of Life ( Time effect : F = 6.79 ; p = 0.002 ) , improved digit span ( F = 12.93 ; p = 0.001 ) , and inhibitory processes ( Time effect : F = 4.93 ; p = 0.03 ) . Depression was reduced over time in PG only ( Time x Group effect : F = 4.53 ; p = 0.01 ) . Verbal Memory performance remained stable over time in SG , but decreased in PG ( Time x group effect : F = 9.29 ; p = 0.004 ) . CONCLUSION Findings suggest that singing and painting interventions may reduce pain and improve mood , quality of life , and cognition in patients with mild AD , with differential effects of painting for depression and singing for memory performance This study aim ed to investigate the effects of weekly singings classes on pulmonary function parameters and quality of life ( QoL ) of COPD patients . Forty-three patients were r and omized to weekly classes of singing practice , or h and craft work . They performed spirometry and completed maximal respiratory pressure measurements , evaluations of dyspnea , and the Saint George ’s Respiratory Question naire , before and after 24 training classes . A functional evaluation , immediately after 10 minutes of singing practice , was also performed at the end of the study . Fifteen subjects completed the study in each group . In comparison to controls the singing group exhibited transitory elevations on the dyspnea Borg scale ( p = 0.02 ) , and inspiratory capacity ( p = 0.01 ) , and decreases of expiratory reserve volume ( p = 0.03 ) , just after a short session of singing . There was a significant difference on changes of maximal expiratory pressures in the comparison between groups at the end of training . While the control group showed deterioration of maximal expiratory pressure , the singing group exhibited a small improvement ( p = 0.05 ) . Both groups showed significant improvements of QoL in within group comparisons . We have concluded that singing classes are a well tolerated activity for selected subjects with COPD . Regular practice of singing may improve QoL , and preserve the maximal expiratory pressure of these patients Background There is some evidence that singing lessons may be of benefit to patients with chronic obstructive pulmonary disease ( COPD ) . It is not clear how much of this benefit is specific to singing and how much relates to the classes being a group activity that addresses social isolation . Methods Patients were r and omised to either singing classes or a film club for eight weeks . Response was assessed quantitatively through health status question naires , measures of breathing control , exercise capacity and physical activity and qualitatively , through structured interviews with a clinical psychologist . Results The singing group ( n=13 mean(SD ) FEV1 44.4(14.4)% predicted ) and film group ( n=11 FEV1 63.5(25.5)%predicted ) did not differ significantly at baseline . There was a significant difference between the response of the physical component score of the SF-36 , favouring the singing group + 12.9(19.0 ) vs -0.25(11.9 ) ( p=0.02 ) , but no difference in response of the mental component score of the SF-36 , breathing control measures , exercise capacity or daily physical activity . In the qualitative element , positive effects on physical well-being were reported in the singing group but not the film group . ConclusionS inging classes have an impact on health status distinct from that achieved simply by taking part in a group activity . Trials registration Registration Current Controlled Trials - IS RCT Background Despite optimal pharmacological therapy and pulmonary rehabilitation , patients with COPD continue to be breathless . There is a need to develop additional strategies to alleviate symptoms . Learning to sing requires control of breathing and posture and might have benefits that translate into daily life . Methods To test this hypothesis we performed a r and omised controlled trial , comparing a six week course of twice weekly singing classes to usual care , in 28 COPD patients . The experience of singing was assessed in a qualitative fashion , through interviews with a psychologist . In addition , we surveyed patients with chronic respiratory conditions who participated in a series of open singing workshops . Results In the RCT , the physical component score of the SF36 improved in the singers ( n = 15 ) compared to the controls ( n = 13 ) ; + 7.5(14.6 ) vs. -3.8(8.4 ) p = 0.02 . Singers also had a significant fall in HAD anxiety score ; -1.1(2.7 ) vs. + 0.8(1.7 ) p = 0.03 . Singing did not improve single breath counting , breath hold time or shuttle walk distance . In the qualitative element , 8 patients from the singing group were interviewed . Positive effects on physical sensation , general well-being , community/social support and achievement/efficacy emerged as common themes . 150 participants in open workshops completed a question naire . 96 % rated the workshops as " very enjoyable " and 98 % thought the workshop had taught them something about breathing in a different way . 81 % of attendees felt a " marked physical difference " after the workshop . ConclusionS inging classes can improve quality of life measures and anxiety and are viewed as a very positive experience by patients with respiratory disease ; no adverse consequences of participation were observed . Trial Registration Current Controlled Trials - IS RCT N17544114 Objective The purpose of this experimental study was to supplement and exp and on clinical research demonstrating that the provision of social support is associated with lower levels of acute pain . Methods Undergraduates ( 52 men and 49 women ) performed the cold pressor task either alone or accompanied by a friend or stranger who provided active support , passive support , or interaction . Pain perception was measured on a 10-point scale . Results Participants in the active support and passive support conditions reported less pain than participants in the alone and interaction conditions , regardless of whether they were paired with a friend or stranger . Conclusions These data suggest that the presence of an individual who provides passive or active support reduces experimental pain 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 This study explored the impact of group singing on mood , coping , and perceived pain in chronic pain patients attending a multidisciplinary pain clinic . Singers participated in nine 30-minute sessions of small group singing , while comparisons listened to music while exercising . A short form of The Profile of Mood States ( POMS ) was administered before and after selected singing sessions to assess whether singing produced short-term elevations in mood . Results indicated that pre to post difference scores were significantly different between singing and control groups for only one of the 15 mood variables ( i.e. , uneasy ) . To test the longer term impacts of singing the Profile of Mood States , Zung Depression Inventory , Pain Self-Efficacy Question naire , Pain Rating Self-Statement , and Pain Disability Question naire were administered immediately before and after the singing sessions . All inventories other than the POMS were re-administered 6 months later . One-way ANCOVAs indicated that participants who attended the singing sessions showed evidence of postintervention improvements in active coping , relative to those who failed to attend , when preintervention differences in active coping were controlled for . While the singing group showed marked improvements from pre to postintervention on all mood , coping , and perceived pain variables , these improvements were also observed among comparison participants . The results of this study suggest that active singing may have some benefits , in terms of enhancing active coping , though the limitations of the study and small effect sizes observed suggest that further research is required to fully explore such effects OBJECTIVE Deep and slow breathing ( DSB ) techniques , as a component of various relaxation techniques , have been reported as complementary approaches in the treatment of chronic pain syndromes , but the relevance of relaxation for alleviating pain during a breathing intervention was not evaluated so far . METHODS In order to disentangle the effects of relaxation and respiration , we investigated two different DSB techniques at the same respiration rates and depths on pain perception , autonomic activity , and mood in 16 healthy subjects . In the attentive DSB intervention , subjects were asked to breathe guided by a respiratory feedback task requiring a high degree of concentration and constant attention . In the relaxing DSB intervention , the subjects relaxed during the breathing training . The skin conductance levels , indicating sympathetic tone , were measured during the breathing maneuvers . Thermal detection and pain thresholds for cold and hot stimuli and profile of mood states were examined before and after the breathing sessions . RESULTS The mean detection and pain thresholds showed a significant increase result ing from the relaxing DSB , whereas no significant changes of these thresholds were found associated with the attentive DSB . The mean skin conductance levels indicating sympathetic activity decreased significantly during the relaxing DSB intervention but not during the attentive DSB . Both breathing interventions showed similar reductions in negative feelings ( tension , anger , and depression ) . CONCLUSION Our results suggest that the way of breathing decisively influences autonomic and pain processing , thereby identifying DSB in concert with relaxation as the essential feature in the modulation of sympathetic arousal and pain perception Current evidence suggests that participatory arts activities , and particularly group singing , may contribute to the well-being of older people . However , there is currently a paucity of prospect i ve research from the participant perspective . This qualitative study nested within a r and omized controlled trial aim ed to assess participants ’ perspectives of the acceptability and effect on health and well-being of a community singing program for older people . Volunteers recruited to the intervention arm ( n = 131 ) were invited to write comments on their experiences over three data collection points of a 14-week singing program . A sub sample ( n = 19 ) participated in a retrospective semi-structured interview . Data were subjected to content and thematic analysis . Comments and interviews from 128 individuals suggested that the singing groups led to specific , incremental benefits to physical , psychological , social , and community well-being . Benefits tended to tail off after the program ended . Suggestions were made for the future running of such groups OBJECTIVE To explore the effects of singing training on respiratory function , voice , mood , and quality of life for people with quadriplegia . DESIGN R and omized controlled trial . SETTING Large , university-affiliated public hospital , Victoria , Australia . PARTICIPANTS Participants ( N=24 ) with chronic quadriplegia ( C4 - 8 , American Spinal Injury Association grade s A and B ) . INTERVENTIONS The experimental group ( n=13 ) received group singing training 3 times weekly for 12 weeks . The control group ( n=11 ) received group music appreciation and relaxation for 12 weeks . Assessment s were conducted pre , mid- , immediately post- , and 6-months postintervention . MAIN OUTCOME MEASURES St and ard respiratory function testing , surface electromyographic activity from accessory respiratory muscles , sound pressure levels during vocal tasks , assessment s of voice quality ( Perceptual Voice Profile , Multidimensional Voice Profile ) , and Voice H and icap Index , Profile of Mood States , and Assessment of Quality of Life instruments . RESULTS The singing group increased projected speech intensity ( P=.028 ) and maximum phonation length ( P=.007 ) significantly more than the control group . Trends for improvements in respiratory function , muscle strength , and recruitment were also evident for the singing group . These effects were limited by small sample sizes with large intersubject variability . Both groups demonstrated an improvement in mood ( P=.002 ) , which was maintained in the music appreciation and relaxation group after 6 months ( P=.017 ) . CONCLUSIONS Group music therapy can have a positive effect on not only physical outcomes , but also can improve mood , energy , social participation , and quality of life for an at-risk population , such as those with quadriplegia . Specific singing therapy can augment these general improvements by improving vocal intensity BACKGROUND To date , research on music for pain management has focused primarily on listening to prerecorded music for acute pain . Research is needed on the impact of active music therapy interventions on chronic pain management . OBJECTIVE The aim of this mixed methods research study was to determine feasibility and estimates of effect of vocal music therapy for chronic pain management . METHODS Fifty-five inner-city adults , predominantly African Americans , with chronic pain were r and omized to an 8-week vocal music therapy treatment group or waitlist control group . Consent and attrition rates , treatment compliance , and instrument appropriateness/burden were tracked . Physical functioning ( pain interference and general activities ) , self-efficacy , emotional functioning , pain intensity , pain coping , and participant perception of change were measured at baseline , 4 , 8 , and 12 weeks . Focus groups were conducted at the 12-week follow-up . RESULTS The consent rate was 77 % . The attrition rate was 27 % at follow-up . We established acceptability of the intervention . Large effect sizes were obtained for self-efficacy at weeks 8 and 12 ; a moderate effect size was found for pain interference at week 8 ; no improvements were found for general activities and emotional functioning . Moderate effect sizes were obtained for pain intensity and small effect sizes for coping , albeit not statistically significant . Qualitative findings suggested that the treatment result ed in enhanced self-management , motivation , empowerment , a sense of belonging , and reduced isolation . CONCLUSIONS This study suggests that vocal music therapy may be effective in building essential stepping-stones for effective chronic pain management , namely enhanced self-efficacy , motivation , empowerment , and social engagement |
1,232 | 19,821,427 | In the absence of evidence of efficacy for oral fenbufen in acute postoperative pain , its use in this indication is not justified at present . | BACKGROUND Fenbufen is a non-selective non-steroidal anti-inflammatory drug ( NSAID ) , used to treat acute and chronic painful conditions .
There is no known systematic review of its use in acute postoperative pain .
OBJECTIVES To assess efficacy , duration of action , and associated adverse events of single dose oral fenbufen in acute postoperative pain in adults . | Abstract Variability in patients ' response to interventions in pain and other clinical setting s is large . Many explanations such as trial methods , environment or culture have been proposed , but this paper sets out to show that the main cause of the variability may be r and om chance , and that if trials are small their estimate of magnitude of effect may be incorrect , simply because of the r and om play of chance . This is highly relevant to the questions of ‘ How large do trials have to be for statistical accuracy ? ’ and ‘ How large do trials have to be for their results to be clinical ly valid ? ’ The true underlying control event rate ( CER ) and experimental event rate ( EER ) were determined from single‐dose acute pain analgesic trials in over 5000 patients . Trial group size required to obtain statistically significant and clinical ly relevant ( 0.95 probability of number‐needed‐to‐treat within ±0.5 of its true value ) results were computed using these values . Ten thous and trials using these CER and EER values were simulated using varying group sizes to investigate the variation due to r and om chance alone . Most common analgesics have EERs in the range 0.4–0.6 and CER of about 0.19 . With such efficacy , to have a 90 % chance of obtaining a statistically significant result in the correct direction requires group sizes in the range 30–60 . For clinical relevance nearly 500 patients are required in each group . Only with an extremely effective drug ( EER>0.8 ) will we be reasonably sure of obtaining a clinical ly relevant NNT with commonly used group sizes of around 40 patients per treatment arm . The simulated trials showed substantial variation in CER and EER , with the probability of obtaining the correct values improving as group size increased . We contend that much of the variability in control and experimental event rates is due to r and om chance alone . Single small trials are unlikely to be correct . If we want to be sure of getting correct ( clinical ly relevant ) results in clinical trials we must study more patients . Credible estimates of clinical efficacy are only likely to come from large trials or from pooling multiple trials of conventional ( small ) size Background Differences between gastrointestinal and cardiovascular effects of traditional NSAID or cyclooxygenase-2 selective inhibitor ( coxib ) are affected by drug , dose , duration , outcome definition , and patient gastrointestinal and cardiovascular risk factors . We calculated the absolute risk for each effect . Methods We sought studies with large amounts of information to calculate annualised rates for clearly defined gastrointestinal ( complicated upper gastrointestinal perforations , ulcers , or bleeds , but not symptomatic or endoscopic ulcers ) and serious cardiovascular outcomes ( antiplatelet trial collaborators – APTC – outcome of fatal or nonfatal myocardial infa rct ion or stroke , or vascular death ) . Results Meta-analyses and large r and omised trials specifically analysing serious gastrointestinal bleeding or cardiovascular events occurring with five different coxibs had appropriate data . In total there were 439 complicated upper gastrointestinal events in 49,006 patient years of exposure and 948 serious cardiovascular events in 99,400 patient years of exposure . Complicated gastrointestinal events occurred less frequently with coxibs than NSAIDs ; serious cardiovascular events occurred at approximately equal rates . For each coxib , the reduction in complicated upper gastrointestinal events was numerically greater than any increase in APTC events . In the overall comparison , for every 1000 patients treated for a year with coxib rather than NSAID , there would be eight fewer complicated upper gastrointestinal events , but one more fatal or nonfatal heart attack or stroke . Three coxib-NSAID comparisons had sufficient numbers of events for individual comparisons . For every 1000 patients treated for a year with celecoxib rather than an NSAID there would be 12 fewer upper gastrointestinal complications , and two fewer fatal or nonfatal heart attacks or strokes . For rofecoxib there would be six fewer upper gastrointestinal complications , but three more fatal or nonfatal heart attacks or strokes . For lumiracoxib there would be eight fewer upper gastrointestinal complications , but one more fatal or nonfatal heart attack or stroke . Conclusion Calculating annualised event rates for gastrointestinal and cardiovascular harm shows that while complicated gastrointestinal events occur more frequently with NSAIDs than coxibs , serious cardiovascular events occur at approximately equal rates . For each coxib , the reduction in complicated upper gastrointestinal events was numerically greater than any increase in APTC events Abstract A previously established relationship for deriving dichotomous from continuous information in r and omised controlled trials ( RCTs ) of analgesics has been tested using an independent data set . Individual patient information from 18 RCTs of parallel‐group design in acute postoperative pain ( after abdominal , gynaecological and oral surgery ) was used to calculate the percentage of the maximum possible pain relief score ( % maxTOTPAR ) and the proportion of patients with > 50%maxTOTPAR for the different treatments . The relationship between the measures was investigated in 85 treatments with over 3400 patients . In 80 of 85 treatments ( 94 % ) agreement between calculated and actual number of patients with > 50%maxTOTPAR was within four patients per treatment and in 72 ( 85 % ) was within three ( average of 40 patients per treatment , range 21–58 patients ) . Summing the positive and negative differences between actual and calculated numbers of patients with > 50%maxTOTPAR gave an average difference of 0.30 patients per treatment arm . Reports of RCTs of analgesics frequently describe results of studies in the form of mean derived indices , rather than using discontinuous events , such as number or proportion of patients with 50 % pain relief . Because mean data inadequately describe information with a non‐normal distribution , combining mean data in systematic review s may compromise the results . Showing that dichotomous data can reliably be derived from mean data in acute pain studies enables data published as means to be used for quantitative systematic review s which require data in dichotomous form & NA ; Reports of RCTs of analgesics frequently describe results of studies in the form of mean derived indices , rather than using discontinuous events — such as number or proportion of patients with 50 % pain relief . Because mean data inadequately describe information with a non‐normal distribution , combining mean data in systematic review s may compromise the results . Showing that dichotomous data can reliably be derived from mean data , at least in acute pain models , indicates that more meaningful overviews or meta‐ analysis may be possible . This study investigated the relationship between continuous and dichotomous analgesic measures in a set of individual patient data , and then used that relationship to derive dichotomous from continuous information in r and omised controlled trials ( RCTs ) of analgesics . Individual patient information from 13 RCTs of parallel‐group and crossover design in acute postoperative pain was used to calculate the percentage of the maximum possible pain relief score ( % maxTOTPAR ) and the proportion of patients with greater than 50 % pain relief ( > 50%maxTOTPAR ) for the different treatments . The relationship between the measures was investigated in 45 actual treatments and 10 000 treatments simulated using the underlying actual distribution ; 1283 patients had 45 separate treatments . Mean % maxTOTPAR correlated with the proportion of patients with > 50%maxTOTPAR ( r2 = 0.90 ) . The relationship calculated from all the 45 treatments predicted to within three patients the number of patients with more than 50 % pain relief in 42 of 45 treatments , and 98.8 % of 10 000 simulated treatments . For seven effective treatments , actual numbers‐needed‐to‐treat ( NNT ) to achieve > 50%maxTOTPAR compared with placebo were very similar to those derived from calculated data In a double-blind clinical trial a new , non-steroidal anti-inflammatory agent with analgesic properties , Fenbufen , was compared to acetylsalicylic acid ( ASA ) and placebo . Six hundred ( 600 ) out- patients , following surgical removal of an impacted lower wisdom tooth , were divided into three groups and r and omly given either Fenbufen ( 500 mg capsules ) , ASA ( 750 mg capsules ) , or placebo . One capsule was taken immediately after the surgical procedure , followed by another capsule every 6 hours . The duration of treatment was 24 hours . Thus , a total of 4 capsules were taken . Self-evaluation forms were provided to the patients and were returned to the investigators the following day . The results were statistically analyzed . Both Fenbufen and ASA were statistically superior ( p ≤ 0.01 ) to placebo in relieving pain . A comparison of the Fenbufen and ASA groups demonstrated a statistically significant ( p ≤ 0.05 ) superiority for Fenbufen in relieving pain . Also sleep was less disturbed in the Fenbufen group . Side-effects reported were few , minor in character , and fewer in number in the Fenbufen group & 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 Abstract One way to ensure adequate sensitivity for analgesic trials is to test the intervention on patients who have established pain of moderate to severe intensity . The usual criterion is at least moderate pain on a categorical pain intensity scale . When visual analogue scales ( VAS ) are the only pain measure in trials we need to know what point on a VAS represents moderate pain , so that these trials can be included in meta‐ analysis when baseline pain of at least moderate intensity is an inclusion criterion . To investigate this we used individual patient data from 1080 patients from r and omised controlled trials of various analgesics . Baseline pain was measured using a 4‐point categorical pain intensity scale and a pain intensity VAS under identical conditions . The distribution of the VAS scores was examined for 736 patients reporting moderate pain and for 344 reporting severe pain . The VAS scores corresponding to moderate or severe pain were also examined by gender . Baseline VAS scores recorded by patients reporting moderate pain were significantly different from those of patients reporting severe pain . Of the patients reporting moderate pain 85 % scored over 30 mm on the corresponding VAS , with a mean score of 49 mm . For those reporting severe pain 85 % scored over 54 mm with a mean score of 75 mm . There was no difference between the corresponding VAS scores of men and women . Our results indicate that if a patient records a baseline VAS score in excess of 30 mm they would probably have recorded at least moderate pain on a 4‐point categorical scale |
1,233 | 28,823,631 | RESULTS Studies have demonstrated that the coordination is a visually guided goal -directed motor behavior with intension and emotion .
Current cognitive research has proved that feeding requires a large-scale neural network extending over several cortices .
The eye-h and -mouth coordination in the newborn can be regarded as a precursor of subsequent self-feeding , and the coordination is very likely mediated through the underdeveloped but essentially the same network interconnecting cortices as in the adult | BACKGROUND There have been several studies concerning rudimentary coordination of the eyes , h and s , and mouth in the human newborn .
The author attempted to clarify the ontogenetic significance of the coordination during the earliest period of human life through a systematic review .
The neural mechanism underlying the coordination was also discussed based on the current knowledge of cognitive neuroscience . | What are the origins of the efficient language learning abilities that allow humans to acquire their mother tongue in just a few years very early in life ? Although previous studies have identified different mechanisms underlying the acquisition of auditory and speech patterns in older infants and adults , the earliest sensitivities remain unexplored . To address this issue , we investigated the ability of newborns to learn simple repetition-based structures in two optical brain-imaging experiments . In the first experiment , 22 neonates listened to syllable sequences containing immediate repetitions ( ABB ; e.g. , “ mubaba , ” “ penana ” ) , intermixed with r and om control sequences ( ABC ; e.g. , “ mubage , ” “ penaku ” ) . We found increased responses to the repetition sequences in the temporal and left frontal areas , indicating that the newborn brain differentiated the two patterns . The repetition sequences evoked greater activation than the r and om sequences during the first few trials , suggesting the presence of an automatic perceptual mechanism to detect repetitions . In addition , over the subsequent trials , activation increased further in response to the repetition sequences but not in response to the r and om sequences , indicating that recognition of the ABB pattern was enhanced by repeated exposure . In the second experiment , in which nonadjacent repetitions ( ABA ; e.g. , “ bamuba , ” “ napena ” ) were contrasted with the same r and om controls , no discrimination was observed . These findings suggest that newborns are sensitive to certain input configurations in the auditory domain , a perceptual ability that might facilitate later language development In adults , specific neural systems with right-hemispheric weighting are necessary to process pitch , melody , and harmony as well as structure and meaning emerging from musical sequences . It is not known to what extent the specialization of these systems results from long-term exposure to music or from neurobiological constraints . One way to address this question is to examine how these systems function at birth , when auditory experience is minimal . We used functional MRI to measure brain activity in 1- to 3-day-old newborns while they heard excerpts of Western tonal music and altered versions of the same excerpts . Altered versions either included changes of the tonal key or were permanently dissonant . Music evoked predominantly right-hemispheric activations in primary and higher order auditory cortex . During presentation of the altered excerpts , hemodynamic responses were significantly reduced in the rig1ht auditory cortex , and activations emerged in the left inferior frontal cortex and limbic structures . These results demonstrate that the infant brain shows a hemispheric specialization in processing music as early as the first postnatal hours . Results also indicate that the neural architecture underlying music processing in newborns is sensitive to changes in tonal key as well as to differences in consonance and dissonance The hypothesis that the ability to coordinate information between tactual and visual modalities is present at birth and dependent on perceptual inherent structures was tested in human newborns . Using an intersensory paired-preference procedure , we showed that newborns can visually recognize the shape of an object that they have previously manipulated with their right h and , out of sight . This is an experimental evidence that newborns can extract shape information in a tactual format and transform it in a visual format before they have had the opportunity to learn from the pairings of visual and tactual experience . This is contrary to a host of theories and models of perceptual learning , both traditional ( empiricist philosophers ) and modern ( connectionist ) |
1,234 | 28,430,621 | Further subgroup analysis revealed that the significance of the association between LVI and worse prognosis in CRC patients is not affected by below factors , including geographic setting , LVI positive rate , treatment , tumor site , and quality of the study .
The current meta- analysis suggests that LVI may be a poor prognostic factor for stage I/II CRC patients | The prognostic value of lymphovascular invasion ( LVI ) in stage I/II colorectal cancer ( CRC ) does not reach a consensus . | Background Lymphovascular invasion ( LVI ) in colorectal cancer ( CRC ) is considered a strong stage-independent prognostic factor and influences decisions regarding adjuvant chemotherapy in patients with stage II tumors . However , the degree of interobserver agreement among pathologists for LVI in CRC is largely unknown . This study was undertaken to examine such interobserver variability , and we hypothesized that the use of immunohistochemical markers for vascular and lymphatic channels could improve interobserver agreement . Design Fifty cases of American Joint Committee on Cancer stage II moderately differentiated CRC from 1990 to 2005 from the pathology archives were selected ; mucinous , medullary , and other recognized special subtypes were excluded . Fifty hematoxylin and eosin ( H&E ) slides ( 1 from each case ) were circulated to 6 gastrointestinal pathologists , who independently assessed small and large vessel invasion . No diagnostic guidelines were given to the participating pathologists ; each was instructed to apply the criteria for LVI that he or she used in daily practice . Immunohistochemistry ( IHC ) for D2 - 40 and CD31 was performed on corresponding paraffin blocks . The IHC slides were r and omized , recirculated , and rescored for LVI . Results were analyzed by kappa ( κ ) statistics , which correct for agreement by chance , and for percentage agreement . Results The average κ values were determined for the H&E slides ( large and small vessel ) , CD31 ( small vessel ) , and D2 - 40 ( small vessel ) ( Fig. 1 ) . Agreement was fair for H&E small vessel invasion [ κ=0.28 ; 95 % confidence interval ( CI ) : 0.22 - 0.34 ] . The least agreement was seen in interpretation of H&E large vessel invasion ( κ=0.18 ; 95%CI : 0.11 - 0.26 ) . Agreement was not improved by use of immunohistochemical stains : CD31 ( large vessel , κ=0.42 , 95%CI : 0.20 - 0.63 , small vessel , κ=0.26 , 95%CI : 0.10 - 0.42 ) and D2 - 40 ( κ=0.32 , 95%CI : 0.21 - 0.42 ) . Conclusions Interobserver variability in diagnosis of LVI was substantial on H&E slides and did not improve upon use of IHC . Agreement in evaluation of large vessel invasion was only slightly higher than would be seen by chance alone . This study highlights the need for criteria in evaluation of LVI , as this assessment may impact patient prognosis and thus change the course of clinical treatment Background Lymph node status is the most important prognostic factor for colorectal cancer . The number of lymph nodes that should be histologically examined has been controversial . The aims of this study were to assess the impact of the number of lymph nodes examined on survival of patients with stage II colorectal cancer and to determine the optimal number of lymph nodes that should be examined . Methods The study included 664 patients who underwent resection for stage II colorectal cancer . The clinical and histopathologic data of the patients were prospect ively collected and analyzed . Results The median number of lymph nodes examined was 12 ( range : 1 to 58 ) . The 5-year disease free survival rate was significantly higher for patients with 12 or more lymph nodes examined compared to those with less than 12 lymph nodes examined . The significant difference in 5-year disease free survival persisted if the dividing number increased progressively from 12 to 23 . However , the difference in survival was most significant ( lowest p value and highest hazard ratio ) for the number 21 . The 5-year disease free survival of patients with 21 or more lymph nodes examined was 80 % whereas that of patients with less than 21 lymph nodes examined was 60 % ( p = 0.001 , hazard ratio 2.08 ) . Multivariate analysis showed that 21 or more lymph nodes examined was a factor that independently influenced survival . The 5-year disease free survival also increased progressively with the number of lymph node examined up to the number 21 . After the number 21 , the survival rate did not increase further . It was likely that 21 was the optimal number , at and above which the chance of lymph node metastasis was minimal . Conclusions The number of lymph nodes examined in colorectal cancer specimen significantly influences survival . It is recommended that at least 21 lymph nodes should be examined for accurate diagnosis of stage II colorectal cancer BACKGROUND The aim of the QUASAR trial was to determine the size and duration of any survival benefit from adjuvant chemotherapy for patients with colorectal cancer at low risk of recurrence , for whom the indication for such treatment is unclear . METHODS After apparently curative resections of colon or rectal cancer , 3239 patients ( 2963 [ 91 % ] with stage II [ node negative ] disease , 2291 [ 71 % ] with colon cancer , median age 63 [ IQR 56 - 68 ] years ) enrolled between May , 1994 , and December , 2003 , from 150 centres in 19 countries were r and omly assigned to receive chemotherapy with fluorouracil and folinic acid ( n=1622 ) or to observation ( with chemotherapy considered on recurrence ; n=1617 ) . Chemotherapy was delivered as six 5-day courses every 4 weeks or as 30 once-weekly courses of intravenous fluorouracil ( 370 mg/m2 ) with high-dose ( 175 mg ) L-folinic acid or low-dose ( 25 mg ) L-folinic acid . Until 1997 , levamisole ( 12 courses of 450 mg over 3 days repeated every 2 weeks ) or placebo was added . After 1997 , patients who were assigned to receive chemotherapy were given fluorouracil and low-dose folinic acid only . The primary outcome was all-cause mortality . Analyses were done by intention to treat . This trial is registered with the International Clinical Trial Registry , number IS RCT N82375386 . FINDINGS At the time of analysis , 61 ( 3.8 % ) patients in the chemotherapy group and 50 ( 3.1 % ) in the observation group had missing follow-up . After a median follow-up of 5.5 ( range 0 - 10.6 ) years , there were 311 deaths in the chemotherapy group and 370 in the observation group ; the relative risk of death from any cause with chemotherapy versus observation alone was 0.82 ( 95 % CI 0.70 - 0.95 ; p=0.008 ) . There were 293 recurrences in the chemotherapy group and 359 in the observation group ; the relative risk of recurrence with chemotherapy versus observation alone was 0.78 ( 0.67 - 0.91 ; p=0.001 ) . Treatment efficacy did not differ significantly by tumour site , stage , sex , age , or chemotherapy schedule . Eight ( 0.5 % ) patients in the chemotherapy group and four ( 0.25 % ) in the observation group died from non-colorectal cancer causes within 30 weeks of r and omisation ; only one of these deaths was deemed to be possibly chemotherapy related . INTERPRETATION Chemotherapy with fluorouracil and folinic acid could improve survival of patients with stage II colorectal cancer , although the absolute improvements are small : assuming 5-year mortality without chemotherapy is 20 % , the relative risk of death seen here translates into an absolute improvement in survival of 3.6 % ( 95 % CI 1.0 - 6.0 ) Background Colorectal carcinoma is the most common malignancy of the gastrointestinal tract . It remains controversial for adjuvant chemotherapy in patients with stage II colon cancer . This study was design ed to identify the risk factors of tumor recurrence in stage II colon cancer . Furthermore , the benefit of adjuvant chemotherapy for high-risk stage II colorectal cancer will be investigated . Material s and methods From May 1998 until August 2004 , 375 patients with stage II ( T3N0M0 , T4N0M0 ) colon cancer received curative operation in a single hospital . The clinical data were extracted from the prospect ively collected colorectal cancer data base . The disease-free survival curves were calculated with Kaplan – Meier ’s analysis , and the survival difference was determined by log-rank test . The p value less than 0.05 was considered to be significant . Results Of 375 stage II colon cancer , 66 patients received 5-FU-based adjuvant chemotherapy , either oral or intravenous ( IV ) form . Within the median of 48.5 months of follow-up , recurrence developed in 35 patients ( 9.3 % ) . T4 lesion ( p=0.024 ) , lymphovascular invasion ( p=0.022 ) , obstruction at presentation ( p=0.008 ) , and mucinous component more than 50 % ( p=0.032 ) were associated with significantly decreased disease-free survival . High-risk patients ( n=102 ) , but not other patients with stage II colon cancer , benefited from adjuvant therapy ( 3-year disease-free survival : 96.4 % vs. 84.7 % , p=0.045 ; 5-year overall survival : 100 % vs. 86.4 % , p=0.015 ) . Conclusion Adjuvant therapy for high-risk stage II colon cancer may be beneficial , and we suggest adjuvant therapy should be considered in high-risk stage II colon cancer patients PURPOSE A greater underst and ing of the biology of tumor recurrence should improve adjuvant treatment decision making . We conducted a validation study of the 12-gene recurrence score ( RS ) , a quantitative assay integrating stromal response and cell cycle gene expression , in tumor specimens from patients enrolled onto Cancer and Leukemia Group B ( CALGB ) 9581 . PATIENTS AND METHODS CALGB 9581 r and omly assigned 1,713 patients with stage II colon cancer to treatment with edrecolomab or observation and found no survival difference . The analysis reported here included all patients with available tissue and recurrence ( n = 162 ) and a r and om ( approximately 1:3 ) selection of nonrecurring patients . RS was assessed in 690 formalin-fixed paraffin-embedded tumor sample s with quantitative reverse transcriptase polymerase chain reaction by using prespecified genes and a previously vali date d algorithm . Association of RS and recurrence was analyzed by weighted Cox proportional hazards regression . RESULTS Continuous RS was significantly associated with risk of recurrence ( P = .013 ) as was mismatch repair ( MMR ) gene deficiency ( P = .044 ) . In multivariate analyses , RS was the strongest predictor of recurrence ( P = .004 ) , independent of T stage , MMR , number of nodes examined , grade , and lymphovascular invasion . In T3 MMR-intact ( MMR-I ) patients , prespecified low and high RS groups had average 5-year recurrence risks of 13 % ( 95 % CI , 10 % to 16 % ) and 21 % ( 95 % CI , 16 % to 26 % ) , respectively . CONCLUSION The 12-gene RS predicts recurrence in stage II colon cancer in CALGB 9581 . This is consistent with the importance of stromal response and cell cycle gene expression in colon tumor recurrence . RS appears to be most discerning for patients with T3 MMR-I tumors , although markers such as grade and lymphovascular invasion did not add value in this subset of patients BACKGROUND A high-risk group of patients with stage II colon cancer has been identified by the results of studies in Western population s. The aim of this study was to investigate the prognostic factors of adjuvant chemotherapy in Turkish patients with stage II colon cancer . METHODS A total of 554 stage II colon cancer patients were retrospectively enrolled in the study . Three hundred fifty-three patients had received adjuvant chemotherapy ( 5-FU-LV , FOLFOX or FLOX ) and 201 had received no adjuvant chemotherapy . T4 tumor stage , lymphovascular invasion , perineural invasion , bowel obstruction and /or perforation , < 12 harvested lymph nodes , and poor differentiation were defined as high-risk factors . RESULTS The median age of the patients was 62 years ( range 26 - 88 ) . The median disease-free survival ( DFS ) was 58.1 months ( 95 % CI , 47.6 months to 68.5 months ) in the non-treatment group and has not been reached in the treatment group ( P < 0.01 ) . In univariate analysis , patient age > 60 years and T4 tumor stage were statistically significant factors that affected DFS as poor prognostic factors . Adjuvant chemotherapy reduced the risk of recurrence with statistical significance ( P < 0.01 ) . In multivariate analysis , patient age > 60 years and T4 tumor stage were independent risk factors affecting DFS . In addition , adjuvant chemotherapy was an independent favorable prognostic factor for DFS ( P < 0.01 ) . CONCLUSIONS Clinical and pathological risk factors in patients with stage II colon cancer may be different in the Turkish population compared to other population s. Further prospect i ve studies in colon cancer are needed to underst and the differences in biology and risk factors between races Abstract Background : T3N0 colon cancer is the target of many adjuvant studies . Very few studies have examined the relationship of the number of lymph nodes examined to the prognosis of this stage . We examined data from the National Cancer Data Base ( NCDB ) to determine whether the number of examined lymph nodes is prognostic for T3N0 colon cancer . Methods : A total of 35,787 prospect ively collected cases of T3N0 colon cancer that were surgically treated and pathologically reported from 1985 to 1991 to the NCDB as T3N0M0 were analyzed . Results : The 5-year relative survival rate for T3N0M0 colon cancer varied from 64 % if 1 or 2 lymph nodes were examined to 86 % if > 25 lymph nodes were examined . Three strata of lymph nodes ( 1–7 , 8–12 , and ≥13 ) distinguished significantly different observed 5-year survival rates . Conclusions : These results demonstrate that the prognosis of T3N0 colon cancer is dependent on the number of lymph nodes examined . A minimum of 13 lymph nodes should be examined to label a T3 colon cancer as node negative . These data suggest that adjuvant trials for T3N0 colon cancer should stratify according to the number of lymph nodes examined Purpose Adjuvant therapy for Stage II colon cancer remains controversial but may be considered for patients with high-risk features . The purpose of this study was to assess the prognostic significance of commonly reported clinicopathologic features of Stage II colon cancer to identify high-risk patients . Methods We analyzed a prospect ively maintained data base of patients with colon cancer who underwent surgical treatment from 1990 to 2001 at a single specialty center . We identified 448 patients with Stage II colon cancer who had been treated by curative resection alone , without postoperative chemotherapy . Results With median follow-up of 53 months , 5-year disease-specific survival for this cohort was 91 percent . Univariate and multivariate analyses identified three independent features that significantly affected disease-specific survival : tumor Stage T4 ( hazard ratio ( HR ) , 2.7 ; 95 percent confidence interval ( CI ) , 1.1–6.2 ; P = 0.02 ) , preoperative carcinoembryonic antigen > 5 ng/ml ( HR , 2.1 ; 95 percent CI , 1.1–4.1 ; P = 0.02 ) , and presence of lymphovascular or perineural invasion ( HR , 2.1 ; 95 percent CI , 1–4.4 ; P = 0.04 ) . Five-year disease-specific survival for patients without any of the above poor prognostic features was 95 percent ; five-year disease-specific survival for patients with one of these poor prognostic features was 85 percent ; and five-year disease-specific survival for patients with ≥2 poor prognostic features was 57 percent . Conclusions Patients with Stage II colon cancer generally have an excellent prognosis . However , the presence of multiple adverse prognostic factors identifies a high-risk subgroup . Use of commonly reported clinicopathologic features accurately stratifies Stage II colon cancer by disease-specific survival . Those identified as high-risk patients can be considered for adjuvant chemotherapy and /or enrollment in investigational trials BACKGROUND The degree of lymph node metastasis represents an important prognostic factor for cancer . Lymphovascular invasion is a traditional tool for estimating the aggressiveness of colorectal cancer . AIM To determine correlations between lymphatic invasion and lymph node metastasis or disease stage , and clarify the prognostic impact of lymphatic invasion . PATIENTS AND METHODS Patients ( N=1,616 ) who underwent curative resection of primary colorectal adenocarcinoma at the Kurume University Hospital were included . Lymphatic invasion was calculated as an average and the degree was also determined ( Ly0 - 3 ) . Clinicopathological factors including lymphatic invasion were assessed by uni- and multivariate analyses to determine factors affecting survival . Survival was compared between different degrees of lymphatic invasion and lymph node metastasis . RESULTS Lymphatic invasion was absent ( Ly0 ) in 806 patients ( 50 % ) , and lymph node metastasis was absent ( N0 ) in 1,085 patients ( 67 % ) . Ninety-one percent of N0 patients were Ly0 - 1 , 72 % of N1 were Ly0 - 1 , and 54 % of N2 were Ly2 - 3 . All patients with stage 0 disease ( 100 % ) were Ly0 , 95 % of stage I were Ly0 - 1 , 46 % of stage II were Ly1 - 2 , and 36 % of stage III were Ly2 - 3 . Five- and 10-year survival rates were 83 % and 68 % in Ly0 , 73 % and 56 % in Ly1 , 66 % and 49 % in Ly2 , 63 % and 48 % in Ly3 , 81 % and 67 % in N0 , 69 % and 57 % in N1 , and 60 % and 52 % in N2 , respectively ( p<0.0001 each ) . CONCLUSION Lymphatic invasion in colorectal cancer correlates well with the status of lymph node metastasis and disease stage , representing an independent prognostic factor after curative resection . Lymphatic invasion can be used for evaluating tumor aggressiveness and estimating patient survival , irrespective of the actual number of positive lymph nodes found PURPOSE : It remains unclear whether lymphovascular invasion marks a poor prognosis for patients with sporadic colorectal cancers . Here , we analyzed the association between lymphovascular invasion and the clinicopathological features and prognosis of sporadic colorectal cancer patients . METHODS : The clinicopathological features and prognosis of 2417 patients with sporadic primary colorectal cancer who underwent an operation at the Asan Medical Center between January 1998 and December 2002 were examined . The patients ' clinicopathological parameters and follow-up and survival data were obtained from a prospect ively collected data base . RESULTS : Of the 2417 patients , a lymphovascular invasion-positive tumor was detected in 610 ( 25.2 % ) . Compared with patients with lymphovascular invasion-negative tumors those with lymphovascular invasion-positive tumors were older ( P < .001 ) and had higher preoperative serum carcinoembryonic antigen levels ( P = .011 ) . Their tumors were also more likely to be poorly differentiated ( P < .001 ) and more advanced in terms of T and N categories ( P < .001 and P < .001 , respectively ) . The lymphovascular invasion-positive tumors were also more likely to have metastasized systemically ( P < .001 ) . Although lymphovascular invasion-positive and lymphovascular invasion-negative tumors metastasized equally frequently to the liver , lung , peritoneum , and bone , lymphovascular invasion-positive tumors metastasized to systemic lymph nodes more often ( P < .001 ) . These tumors also recurred at systemic lymph nodes after curative intent surgery more often ( P = .007 ) . Lymphovascular invasion-positive status was an independent unfavorable prognostic factor for the 5-year overall and 5-year disease-free survival of patients with sporadic colorectal cancer ( P < .001 and P < .001 , respectively ) . CONCLUSION : Lymphovascular invasion-positive status could be used to identify patients with sporadic primary colorectal cancer with aggressive tumors and as a factor that independently indicates an unfavorable prognosis Background In colorectal cancer , the morphology of the invasive tumor margin may reflect aggressiveness of tumor growth , thus providing important prognostic information . The tumor growth pattern according to Jass and the extent of tumor budding were analyzed in patients with American Joint Committee on Cancer/Union for International Cancer Control ( AJCC/UICC ) stage II disease . Methods Tumors of 120 r and omly selected patients with AJCC/UICC stage II disease were retrospectively review ed for tumor growth pattern ( exp and ing vs. infiltrating ) and the extent of tumor budding , with high- grade budding reflecting presence of 10 or more budding foci scattered at the invasive tumor margin . Progression-free and cancer-specific survivals were determined by the Kaplan – Meier method . For multivariable analysis , Cox ’s proportional hazards regression models were performed . Results The infiltrating growth pattern was significantly associated with histological subtype and lymphovascular invasion , while high- grade budding was significantly associated with tumor grade and lymphovascular invasion . High- grade budding , but not the infiltrating growth pattern , was significantly associated with outcome in univariable analysis . Cox ’s proportional hazards regression models proved tumor budding to be an independent predictor of disease progression ( hazard ratio 3.91 , 95 % confidence interval 1.3–11.77 ; P = 0.02 ) and cancer-related death ( hazard ratio 5.90 , 95 % confidence interval 1.62–21.51 ; P = 0.007 ) . The combination of infiltrating growth pattern and high- grade budding did not have a stronger prognostic significance than tumor budding alone . Conclusions Tumor budding independently predicted patient outcome in patients with AJCC/UICC stage II colorectal cancer and may therefore be used for accurate prognostication , patient counseling , and design of clinical trials by using integrated multimodal therapy AIM Adjuvant therapy is not routinely recommended in UICC stages I and II colon cancer , but may be considered for high-risk patients . Our aim is to identify clinicopathologic characteristics in colon cancer stages I and II , which are associated with an increased risk of tumour recurrence and tumour-related death . METHODS We analysed our prospect ively documented clinical data base of 775 patients with colon cancer stages I and II , which underwent curative resection between 1982 and 2006 . No adjuvant chemotherapy was applied . The median follow-up time was 80 months . RESULTS For the entire study group , 5- and 10-year tumour-specific survival probabilities were 94.8+/-0.9 % and 91.0+/-1.4 % , respectively . Multivariate analysis identified three tumour characteristics as independent prognostic factors : lymphatic vessel invasion ( p=0.034 ) , poor tumour grading ( G3/G4 ) ( p=0.020 ) and extended tumour length ( 6 cm ) ( p=0.042 ) . Five-year ( 10-year ) tumour-specific survival for patients without any of the poor prognostic tumour characteristics ( ppTCs ) was 96.0 % ( 94.7 % ) . There was a significantly increased risk for tumour-related death with increasing numbers of ppTCs ( p<0.001 ) . While patients with only one ppTC had a 5-year ( 10-year ) tumour-specific survival of 94.8 % ( 88.9 % ) , it decreased to 88.9 % ( 78.4 % ) for patients with two ppTCs ( hazard ratio ( HR ) 3.69 , 95 % confidence interval ( CI ) 1.67 - 8.13 ) and to 87.5 % ( 72.9 % ) for patients with all three ppTCs ( HR 6.56 , 95 % CI 1.50 - 26.62 ) . CONCLUSION Patients with stage I or II colon cancer have a favourable prognosis after radical resection . The presence of two or three poor prognostic tumour characteristics identifies a small patient subgroup ( 12 % ) with an increased risk of tumour-related death that may be considered for adjuvant chemotherapy BACKGROUND This study aim ed to evaluate the oncological outcome of patients who had Stage II rectal cancer and underwent curative nonsphincter-ablation surgery without adjuvant radiation . PATIENTS AND METHODS During the study period from August 1993 to December 2002 , 224 patients ( 141 men ) with Stage II cancer underwent curative anterior resection or Hartmann ’s procedure without adjuvant radiation . Data were collected prospect ively . The oncologic outcomes of these patients were studied and the risk factors for recurrence and survival were analyzed . RESULTS The median age of the patients was 69 ( range , 27–89 ) years and the median level of the tumor from the anal verge was 8 ( range , 3–20 ) cm . Four patients ( 1.8 percent ) died in the postoperative period and postoperative complications occurred in 74 patients ( 33 percent ) . The median follow-up time of the surviving patients was 43.6 months . The actuarial five-year recurrence rate was 25.4 percent , whereas the five-year actuarial local and systemic recurrence rates were 6.1 percent and 20 percent , respectively . On multivariate analysis , independent factors associated with a higher recurrence rate included lymphovascular invasion , perineural invasion , and absence of chemotherapy . The overall and cancer-specific survival rates of the patients were 71.1 percent and 81.1 percent , respectively . On multivariate analysis , only adjuvant chemotherapy ( P = 0.024 ; hazard ratio = 6.04 ; 95 percent confidence interval , 1.27–28.74 ) and the absence of lymphovascular invasion ( P = 0.002 ; hazard ratio = 3.77 ; 95 percent confidence interval , 1.63–8.77 ) were independent factors associated with significantly better cancer-specific survival . CONCLUSION A low local recurrence rate can be achieved in patients with Stage II rectal cancer treated with nonsphincter-ablation surgery without adjuvant radiation . Postoperative chemotherapy is associated with a lower recurrence rate and higher survival rates . Further study is warranted to define the role of adjuvant chemotherapy in patients with rectal cancer |
1,235 | 22,050,830 | Few were design ed to have the ability to be completed by or in conjunction with carers and few were able to distinguish between different types of non-adherence , which limited their ability be used effectively in the continuous improvement of targeted adherence enhancing interventions .
The data available suggested that patients find it easier to estimate general adherence than to report a specific number of doses missed .
Visual analogue scales can be easier for patients than other types of scale but are not suitable for telephone administration . | Background There is a recognised need to build primary care medication adherence services which are tailored to patients ' needs .
Continuous quality improvement of such services requires a regular working method of measuring adherence in order to monitor effectiveness .
Self report has been considered the method of choice for clinical use ; it is cheap , relatively unobtrusive and able to distinguish between intentional and unintentional non-adherence , which have different underlying causes and therefore require different interventions .
A self report adherence measure used in routine clinical practice would ideally be brief , acceptable to patients , valid , reliable , have the ability to distinguish between different types of non-adherence and be able to be completed by or in conjunction with carers where necessary . | Abstract Purpose : To examine the performance of an instrument to assess adherence based on a visual analogue scale , compared to an instrument based on 3-day recall , using unannounced pill counts in the place of residence as the gold st and ard . Method : We prospect ively assessed adherence to antiretroviral therapy in 84 marginally housed indigent HIV-infected patients who were receiving stable antiretroviral therapy in San Francisco , California , with three adherence assessment s over no more than 4 months . Results : Mean adherence using the visual analogue scale , 3-day recall , and unannounced pill count methods were 82.5 % , 84.2 % , and 75.9 % , respectively . The correlation between visual analogue scale and unannounced pill count was high ( r = 0.76 ) and was not statistically different from that between 3-day recall and unannounced pill count ( r = 0.71 ; p = .52 ) . Both methods were also similarly inversely correlated with HIV viral load ( r = -0.49 and -0.34 , respectively ; p = .22 for the difference in the correlations ) . The visual analogue scale correlation with unannounced pill count was stable over time and remained high in all sub population s examined . Conclusion : A visual analogue scale to assess adherence was performed as well as a more complicated 3-day recall instrument in this diverse population . Given its simplicity , the visual analogue scale adherence instrument will be useful in research and may be useful in routine patient care High blood pressure ( HBP ) is one of the most important risk factors for morbidity and mortality in the world . Non-adherence to medication is associated with the lack of control of HBP . The objective of this study was to assess the validity of four indirect methods for measuring adherence to medication to control HBP in primary health care . A r and om sample of 120 hypertensive patients who were undergoing treatment for at least 2 months in a primary care unit in Florianópolis ( Brazil ) were included in the study . The independent variables were four indirect methods to measure adherence to medication : knowledge regarding the HBP medication , the blood pressure level , attitude regarding the medication intake ( Morisky – Green test ) and self-reported adherence . The classification of HBP was based on criteria established by the Brazilian Ministry of Health . The gold st and ard used for measuring adherence was the pill count . Logistic regression was used to estimate sensitivity ( highest value of 88.2 % for self-report ) , specificity ( highest value of 70.7 % for HBP control ) , positive predictive value ( highest value of 46.4 % for HBP control ) and negative predictive value ( highest value of 79.1 % for Morisky – Green test ) for each of the indirect methods . No indirect method of measuring adherence had a good positive predictive value for adherence , which was best predicted by patients ' age and whether they managed to control HBP . The results also revealed low treatment adherence ( 31.2 % ) and low control of HBP ( 37.6 % ) . Non-adherence was mainly associated with side effects of the treatment AIDS Clinical Trials Group ( ACTG ) 359 was a r and omized , partially double-blinded factorial study of 6 antiretroviral regimens , all including saquinavir , among HIV-infected persons in whom prior therapy had failed ( n = 258 ) . Counts of remaining saquinavir capsules were determined between weeks 0 and 4 ; at weeks 4 , 8 , and 16 , self-reported adherence was estimated from 2-day report of doses skipped , therapeutic coverage , and percent of doses taken were determined by electronic monitoring devices applied to saquinavir bottles , and the saquinavir 24-hour area under the curve ( AUC ) was estimated . Relationships were evaluated among these 4 adherence measures and the primary endpoint of week 16 HIV RNA change . Thirty percent of 254 subjects had HIV RNA ≤500 copies/mL at week 16 . Only self-reported adherence and saquinavir AUC were significantly associated with week 16 HIV RNA change ( P = 0.019 and 0.023 , respectively ) , and these measures were higher in subjects with week 16 HIV RNA ≤500 copies/mL ( P = 0.03 and 0.008 , respectively ) . The ability to detect a correlation between electronically monitored adherence and virologic response was limited by the small sample size . Self-reported adherence and saquinavir AUC were significant predictors of virologic response , in this evaluation . These findings provide insight into methods of assessing and improving adherence to antiretroviral regimens BACKGROUND Nonadherence to physician treatment recommendations is an increasingly recognized cause of adverse outcomes and increased health care costs , particularly among patients with cardiovascular disease . Whether patient self-report can provide an accurate assessment of medication adherence in out patients with stable coronary heart disease is unknown . METHODS We prospect ively evaluated the risk of cardiovascular events associated with self-reported medication nonadherence in 1015 out patients with established coronary heart disease from the Heart and Soul Study . We asked participants a single question : " In the past month , how often did you take your medications as the doctor prescribed ? " Nonadherence was defined as taking medications as prescribed 75 % of the time or less . Cardiovascular events ( coronary heart disease death , myocardial infa rct ion , or stroke ) were identified by review of medical records during 3.9 years of follow-up . We used Cox proportional hazards analysis to determine the risk of adverse cardiovascular events associated with self-reported medication nonadherence . RESULTS Of the 1015 participants , 83 ( 8.2 % ) reported nonadherence to their medications , and 146 ( 14.4 % ) developed cardiovascular events . Nonadherent participants were more likely than adherent participants to develop cardiovascular events during 3.9 years of follow-up ( 22.9 % vs 13.8 % , P = .03 ) . Self-reported nonadherence remained independently predictive of adverse cardiovascular events after adjusting for baseline cardiac disease severity , traditional risk factors , and depressive symptoms ( hazards ratio , 2.3 ; 95 % confidence interval , 1.3 - 4.3 ; P = .006 ) . CONCLUSIONS In out patients with stable coronary heart disease , self-reported medication nonadherence is associated with a greater than 2-fold increased rate of subsequent cardiovascular events . A single question about medication adherence may be a simple and effective method to identify patients at higher risk for adverse cardiovascular events The relationship between adherence to highly active antiretroviral therapy ( HAART ) and RNA-HIV viral load outcomes has been extensively shown . Although there are different procedures for assessing treatment adherence , there is no ideal method . We present the SERAD ( Self-Reported Adherence ) question naire , a qualitative and quantitative self-reported instrument design ed to provide an easier adherence measurement . We also compared the question naire to three other methods to evaluate adherence to HAART regimens in HIV-infected patients . Two prospect i ve , observational , longitudinal studies were developed : a single-center pilot study followed by a multicenter study . A total of 530 HIV-infected out patients was prospect ively included , 66 in the pilot study and 464 in the multicenter study . Four methods were used to study adherence to HAART regimens : the SERAD question naire , pill count , electronic monitoring , and plasma drug monitoring . Pearson 's correlations and Bl and and Altman 's method were developed . The SERAD question naire showed good feasibility and significant validity . Adequate levels of agreement between methods were observed , particularly when adherence was high . Differences increased as adherence fell . Moreover , the question naire was completed correctly , the interviewers did not report uncovered aspects , and the information was collected easily . Our results suggest that the SERAD question naire is a feasible and useful instrument for assessing adherence to HAART regimens in HIV-infected patients , and makes it possible to obtain reliable qualitative and quantitative information related to treatment adherence A step-wise approach to identify valid and feasible methods to detect non-adherence to tuberculosis drugs was evaluated in a prospect i ve study among pulmonary tuberculosis patients in an outpatient clinic in Indonesia . First , adherence was measured by self-reporting with the st and ardized Morisky question naire , physician assessment , pill-count , visit attendance , diary and an electronic medication event monitoring system ( MEMS ) . Next , validity of single methods was assessed against MEMS as gold st and ard . Feasibility of methods was then judged by physicians in the field . Finally , when valid and feasible methods were combined , it appeared that self-reporting by a question naire plus physician assessment could identify all non-adherent patients . It is recommended to use a systematic approach to develop a valid and locally feasible combination of methods to detect non-adherence to TB drugs Nonadherence to immunosuppressants in renal transplant recipients is a major factor affecting graft survival , but it is difficult to detect accurately in clinical practice . Adherence was measured in 153 adult renal transplant recipients using self-report question naires and interview , clinician rating , and cyclosporine levels . The sensitivity and specificity of these measures were determined by comparison with electronic monitoring in a r and omly selected sub sample of 58 subjects . Measures of adherence in current clinical use do not perform well when tested against electronic monitoring . Self-report at a confidential interview was the best measure of adherence for the detection of both missed doses and erratic timing of medication . However , the use of a confidential interview is not directly applicable to a clinical setting . Further research on how best to facilitate disclosure in clinical setting s may be the best way to develop adherence measures for use in routine practice A two-group r and omized experimental design was employed to assess the effects of monitoring and feedback on the compliance of 93 psychiatric out patients treated with lithium . Compliance in both groups was measured using self-report , lithium level , appointment-keeping , and medication refill frequency . The experimental group was also monitored using a unique electronic device that records the time and day pills are removed . At the midpoint of the study , the experimental group received feedback about serum lithium levels and patterns of removing medications from the monitoring device while the control group received feedback about serum lithium levels only . The study demonstrated no sustained effect of the monitoring and feedback interventions on compliance Improved therapeutic strategies , including the introduction of protease inhibitors , have led to a striking decrease in HIV-related morbidity and mortality ( 1 , 2 ) . It is widely believed that adherence to an antiretroviral regimen is central to the likelihood that a patient will derive sustained benefit from therapy ( 3 , 4 ) . Conventional wisdom holds that two groups of patients are currently experiencing clinical and virologic failure . The first group consists of patients who have received multiple different antiretroviral drugs over a prolonged period of time and who may be infected predominantly with HIV strains that are resistant to multiple drugs . The second group comprises patients who adhere poorly to their antiretroviral regimen . The two groups are not mutually exclusive : Patients with suboptimal adherence may be more likely to have antiretroviral drugresistant HIV infection . The potential public health importance of adherence to therapy in prevention of transmission of drug-resistant virus has also been emphasized ( 5 ) . Patients with suboptimal adherence to antiretroviral therapy and poor adherence to use of safer-sex practice s , such as use of condoms , may infect others with their own antiretroviral drugresistant virus . Anecdotal experience suggests that physicians may be unwilling to prescribe combination antiretroviral therapy to patients whom they perceive to be at high risk for poor adherence ( 6 ) . Given the critical importance of adherence to therapy to patient outcome , secondary prevention of HIV infection , and willingness of providers to prescribe therapy , we prospect ively investigated the association between protease inhibitor adherence and patient outcome , factors related to adherence , and the accuracy of physicians ' prediction of patient adherence . We used a microelectronic monitoring system to assess adherence to antiretroviral therapy . Methods Study Sample The study was conducted at the HIV clinics of the Veterans Affairs Medical Center , Pittsburgh , Pennsylvania , and University of Nebraska Medical Center , Omaha , Nebraska . The HIV physicians at these clinics were primary care providers for the study patients . Each site also had a dedicated HIV nurse coordinator . From August 1997 to March 1999 , we enrolled consecutive patients with HIV infection who were already receiving a protease inhibitor ( experienced patients ) or who were to begin taking a protease inhibitor ( naive patients ) . Exclusion criteria were inability to give informed written consent ; expectation of continued use of a medication organizer to include protease inhibitors ; and residence in a nursing home , jail , or hospice , where medications were dispensed at least daily . Collection of Baseline Data At baseline , a study investigator used medical chart review to complete a 52-item question naire for each patient . The question naire covered demographic information ( age , sex , ethnicity , risk factors for HIV infection , educational and employment status , income ) , medical history ( years known to be HIV infected ; opportunistic infections ; history of schizophrenia , depression , or bipolar affective disorder ) , and medication use ( name , dose , and frequency of all antiretroviral agents , other antimicrobials , and other prescription therapies ) . The enrolling physician assessed use of illegal drugs and nonprescription therapies ( including herbal or alternative therapies ) by interview . Alcohol abuse was assessed by using the CAGE question naire ( cutting down , annoyance with criticism , guilty feelings , and use of eye-opener drinks ) ( 7 ) . Information about use of adherence aids ( such as personal reminders by significant others or timers , alarms , or other devices ) was specifically sought . The investigator asked study patients if they felt that their current symptoms were attributable to HIV infection , the antiretroviral medications , or both . In addition , patients were asked whether they agreed with such health beliefs as Do you think your antiretroviral therapy will make you live longer ? At baseline , each patient completed the Beck Depression Inventory and the General Health Question naire ( 8 , 9 ) , well-vali date d measures of psychiatric morbidity that have been widely used in patients with HIV infection ( 9 - 11 ) . Patients completed the inventories as a written task without the assistance of a physician or clinic nurse . At baseline , we used the following question to elicit a prediction of adherence to protease inhibitor therapy from the patient 's primary HIV physician and clinic nurse : Do you think that the patient is compliant with antiretroviral therapy , that is , taking greater than 80 % of the prescribed doses of antiretroviral medications ? This prediction was made after collection of the baseline information but before actual measurement of adherence using the microelectronic monitoring system had begun . Collection of Follow-up Data Every 3 months for the duration of the study , the study participants were asked whether any of the following had changed since their previous visit : employment , use of alcohol or illegal drugs , residence , attribution of symptoms to the antiretroviral therapy or HIV infection , and changes in medications . Patients completed a new Beck Depression Inventory and General Health Question naire . The primary HIV physician determined whether the patient had developed an opportunistic infection in the past 3 months . Laboratory Testing At baseline and every 3 months for the duration of the study , HIV RNA levels were measured by using the Roche Amplicor System ( Roche Diagnostics , Nutley , New Jersey ) and CD4 lymphocyte sub population assays were performed . Assessment of Adherence Adherence was measured by using the Medication Events Monitoring System ( MEMS ) ( Aprex , Union City , California ) . The MEMS TrackCap system consists of st and ard medication bottles that have a pressure-activated microprocessor in the cap ( 12 ) . The microprocessor records each opening and lists the date , time , and duration of opening . The information on medication dosing is retrieved by scanning the cap over a purpose -built communicator module . The information is then stored in a data base provided by Aprex . Although the MEMS TrackCap system can not prove consumption of the drug by the patient , prolonged deception by patients has been shown to be unlikely ( 13 ) . Patients were provided with a MEMS TrackCap bottle for each prescribed protease inhibitor ( including refrigerated ritonavir capsules ) . Use of the MEMS TrackCaps system was not possible for patients who were prescribed ritonavir from August 1998 onward because ritonavir capsules were no longer available . The patients could use their regular medication organizer for all other medications . The caps were scanned each time the patient presented to the HIV clinic . Patients were specifically instructed not to take extra doses out at any time ( for example , not to take out an extra dose in the morning for consumption at lunchtime ) . Patients were offered small pill bottles that could be easily carried in a coat pocket . Adherence rates were defined as the number of doses recorded by the MEMS TrackCap divided by the total number of doses prescribed during the monitoring period . To evaluate the effect of dosing frequency on adherence , dosing interval errors were defined as medication doses taken at a time other than that prescribed ( that is,<9 hours or>15 hours after the previous dose of a medication prescribed every 12 hours or<5 hours or>11 hours after the previous dose of a medication prescribed every 8 hours ) ( 12 ) . Definitions of Virologic and Clinical Outcomes Virologic failure was defined as an HIV RNA level greater than 400 copies/mL at the last study visit . Changes in CD4 lymphocyte counts were calculated as the difference between the count at the baseline visit and the count at the final study visit . Opportunistic infections were defined according to Centers for Disease Control and Prevention criteria ( 14 ) . Hospitalization for all causes was recorded as the number of nights spent in any acute-care hospital ; nursing homes and drug or alcohol rehabilitation facilities were excluded . Mortality was defined as all-cause mortality at any time during the study period . Statistical Analysis All data was entered into a computerized data base , PROPHET Statistics Version 6.0 ( AB Tech Corp. , Charlottesville , Virginia ) . The chi-square or Fisher test was used to compare categorical variables . Continuous variables were examined by using the t-test or the MannWhitney test . Baseline and follow-up values were compared by using the paired t-test or the Wilcoxon signed-rank test . To examine the relation between two continuous measures , a best-fit line was obtained . The slope of this line was then tested against the null hypothesis of a slope of zero . The Pearson correlation coefficient was also calculated . Cox proportional-hazards regression was used to evaluate the relation between adherence and time to virologic failure . In the Cox model , predictor variables found to be significant ( P<0.1 ) in univariate analysis were added to the model . Logistic regression models were used to assess the effects of multiple variables on adherence . Factors were entered into the regression model if they were found by univariate analysis to be significantly associated ( P<0.1 ) . To analyze time to return of detectable HIV RNA for patients with an undetectable viral load at baseline , KaplanMeier survival curves were computed for less than 95 % adherence and 95 % or greater adherence and were compared by using the MantelCox test . The McNemar test was used to compare the predictions of the clinical nurses and physicians . Ethical Considerations The study was approved by the institutional review boards of the two study centers . Patients were fully informed that their adherence to protease inhibitor therapy was being measured by using the MEMS TrackCap system . Results Patient Characteristics Of 99 patients enrolled in the study , 6 withdrew before follow-up data were collected ( AIMS To assess the advantages and disadvantages of four methods for study ing compliance with antidepressants : self-report scores , tablet counts , a microprocessor ( MEMS ) container system and the assay of nordothiepin and dothiepin concentrations in plasma . METHODS The techniques were used in 88 patients commencing tricyclic antidepressants in the setting of UK general practice . RESULTS The MEMS system proved to be the most informative technique allowing identification of the precise time of container opening , the demonstration of ' drug holidays ' and early cessation of therapy . Self-report scores ( Morisky ) proved a useful screening technique with a sensitivity of 72.2 % and specificity of 74.1 % for > or = 80 % compliance . Although tablet counts were possible in 84 patients ( 95 . 5 % ) they were unreliable in 19 ( 21.6 % ) . Blood concentration assays proved the least acceptable method to patients and were possible in only 53 ( 60.2 % ) . A ratio of nordothiepin : dothiepin > or = 1.1 cl aim ed , by others , to identify noncompliance was only reliable when concentrations were low . CONCLUSIONS Both the MEMS system and self-report scores proved useful methods for identifying noncompliant patients in the setting of UK general practice . Although compliance was higher than reported in previous studies with 70 patients ( 79.5 % ) completing 6 weeks treatment , general practitioners tended to prescribe subtherapeutic doses OBJECTIVES ( 1 ) To document rates and patterns of adherence from enrollment until week 24 of an AIDS clinical trial ; ( 2 ) to examine the association of adherence to clinical end-points including plasma HIV-1 RNA level and CD4 cell count ; and ( 3 ) to identify predictors of adherence from clinical , behavioural , psychosocial and demographic factors . DESIGN Sub- study of a multicentre , r and omised , open-label , comparison-controlled trial ; 21 collaborating units of the Adult AIDS Clinical Trials Group . Observational , prospect i ve analysis . METHODS Ninety-three subjects with baseline plasma HIV-1 RNA levels > 500 copies/ml , who completed clinical assessment , plasma HIV-1 RNA titres and CD4 cell counts at study entry , weeks 2 , 4 and every 4 weeks thereafter until week 24 . All patients were antiretroviral-experienced but were naive to non-nucleoside reverse transcriptase inhibitors and protease inhibitors . Self-reported adherence to antiretroviral therapies prescribed as part of the trial was assessed every 4 weeks from trial , week 4 until week 24 . RESULTS Average adherence was high , with 63 % of subjects reporting > 95 % adherence across the trial . However , there was a significant decline in adherence over time on trial . After controlling for potential confounding variables , patients who were less than 95 % adherent to medications were 3.5-times more likely to have treatment failure ( HIV-1 RNA > 50 copies/ml ) than subjects with adherence rates of 95 - 100 % . The strongest predictor of adherence was adverse clinical events ( for example , dermatological , gastrointestinal symptoms ) : patients with adverse events were 12.8-times less likely to have 95 - 100 % adherence . Other clinical , demographic , psychosocial and behavioural factors were also significant predictors of adherence . CONCLUSIONS Adherence influences virological outcome even in AIDS clinical trials where overall adherence rates are high and should therefore be monitored in future trials . Intervention may be warranted to enhance adherence for subjects who have early toxicities , express concern about taking medications as directed , and for women and minorities Abstract Objective : To assess the effectiveness of a simplified therapy for very nonadherent patients who had previously failed with HAART . Method : We performed a prospect i ve open-label study of antiretroviral-experienced patients . Dosing schedule comprised ( co-formulated ) zidovudine , lamivudine , and abacavir bid . Eligible patients had to have plasma HIV RNA > 5000 copies/mL , previous therapy , and very poor adherence to the medication regimen . Results : Eighty-five patients were included ( mean viral load , 4.4 log/mL ; mean CD4 , 240 cells/mL ; IDUs , 78 % ; methadone maintenance program , 42 % ; AIDS , 28 % ) . Number of previous therapies : one , 53 % ; two , 28 % ; three or more , 19 % . In the intent-to-treat analysis at 1 year , 38 patients ( 44.7 % ) achieved viral load below 500 copies/mL. Adherence greater than 90 % of prescribed drugs was reported in 49 % of patients , adverse events were reported in 17.6 % , mortality in 6 % , and lost to follow-up in 26 % . The factors associated with virologic failure were nonadherence ( odds ratio [ OR ] , 4.4 ; 95 % CI 1.5 - 12.3 ) , baseline CD4 cell count < 200 cells/mL ( OR , 3.4 ; 95 % CI 1.3 - 8.9 ; p = .01 ) , and more than one previous treatment ( OR , 2.7 ; 95 % CI 1.1 - 6.9 ) . Conclusion : Regarding previously very nonadherent patients , this simplified combination therapy containing three NRTIs obtained satisfactory results in ART-experienced patients . However , more aggressive interventions to enhance adherence are needed to improve results Background : The ASK-20 survey is a previously vali date d patient-report measure of barriers to medication adherence and adherence-related behavior . Objective : To derive and vali date a shorter version of the ASK-20 scale . Methods : Patients with asthma , diabetes , and congestive heart failure were recruited from a university medical center . Participants completed the ASK-20 survey and other question naires . Approximately one-third of participants were r and omized to a 2-week retest administration . Item performance and results of an exploratory factor analysis were examined for item reduction and subscale identification . Subsequent analyses examined reliability and validity of the shorter version of the ASK . Results : A total of 112 patients participated ( 75.9 % female ; mean age 46.7 y ; 53.6 % African American ) . Eight items were dropped from the ASK-20 based on factor loadings , floor effects , Cronbach 's α , and the ability of each item to discriminate between groups of patients differing in self-reported adherence . The new total score ( ASK-12 ) had good internal consistency reliability ( Cronbach 's α 0.75 ) and test-retest reliability ( intraclass correlation 0.79 ) . Convergent validity was demonstrated through correlations with the Morisky Medication Adherence Scale ( r -0.74 ; p < 0.001 ) , condition-specific measures , the SF-12 Mental Component Score ( r –.32 ; p < 0.01 ) , and proportion of days covered by tilled medication prescriptions in the past 6 months as indicated by pharmacy cl aims data ( r -0.20 ; p = 0.059 ) . The ASK-12 total score also discriminated among groups of patients who differed in self-reported adherence indicators , including whether a dose was missed in the past week , the number of days medication was not taken as directed , and treatment satisfaction . Three subscales were identified ( adherence behavior , health beliefs , inconvenience/forgetfulness ) , and results provided initial support for their validity . Conclusions : The ASK-12 demonstrated adequate reliability and validity , and it may be a useful brief measure of adherence behavior and barriers to treatment adherence OBJECTIVE : To compare medication adherence calculated from four different data sources including a pill count and self-report obtained during a home medication history , as well as calculations based on refill frequency derived from a provincial prescription cl aims data base ( manual and electronic ) . DESIGN : Baseline medication adherence was collected as part of a prospect i ve , r and omized , controlled study . Mean medication adherence results obtained from the four data sources were compared using repeated- measures ANOVA followed by a Tukey 's multiple range test . SETTING : A pharmacy consultation service located at an interdisciplinary wellness center for noninstitutionalized elderly . PATIENTS : 65 years or older , noninstitutionalized , taking one or more prescribed or nonprescribed medications . Clients would either present to the wellness center or be referred by the Provincial Home Care program . RESULTS : When calculated from self-report or manual or electronic prescription cl aims data , mean percent adherence by drug was high and not statistically different ( 95.8 % ± 17.1 % , 107.6 % ± 40.3 % , and 94.6 % ± 24.0 % , respectively ) , whereas the pill count adherence was significantly lower at 74.0 % ± 41.5 % ( p < 0.0001 ) . CONCLUSIONS : An unexpected finding was that the pill count technique used in this study of elderly clients using chronic , repeat medications appeared to underestimate medication adherence . Numerous other limitations of pill count , self-report , and a province-wide prescription cl aims data base in estimating medication adherence are presented . When using medication adherence as a process measure , the research er and practitioner should be aware of the limitations unique to the data source they choose , and interpret data cautiously Among HIV-infected persons , high-level adherence to antiretroviral medications ( > 90%-95 % ) is associated with improved immunologic , virologic , and clinical outcomes , and is necessary to prevent the emergence of viral resistance . This study examines whether lifetime traumatic events including physical and sexual abuse , are associated with antiretroviral nonadherence . We present a cross-sectional analysis of the Coping with HIV/AIDS in the Southeast ( CHASE ) Study , analyzing data from the enrollment interview and medical records of study subjects . The CHASE Study is a prospect i ve cohort study of consecutively sample d HIV-infected subjects from infectious diseases clinics in five southern states ; Alabama , Georgia , Louisiana , North Carolina , and South Carolina . Four hundred seventy-four ( 78 % ) of the 611 CHASE study subjects reported being treated with antiretroviral medications at enrollment and are included in this analysis . Nonadherence was defined as the patient 's self-report of missing any doses of their antiretroviral medications over the previous 7 days . Among study subjects , 54 % reported a history of physical and /or sexual abuse , 91 % reported at least one lifetime traumatic event , and 24 % reported nonadherence with their antiretrovirals . In multivariable logistic regression analysis , the number of categories of lifetime traumatic events ( p = 0.03 ) , the Addiction Severity Index ( ASI ) alcohol score ( p = 0.02 ) , and being uninsured ( p = 0.04 ) were associated with antiretroviral nonadherence . The finding that lifetime traumatic events are associated with antiretroviral nonadherence , particularly among those who have been traumatized in multiple ways , highlights the complex and often persisting manifestations of such trauma and calls for further investigation Background : Little is known about adherence to pediatric antiretroviral regimens in countries of the developing world . Both assessment methods and predictors of adherence need to be examined to deliver appropriate health care to the growing patient population in re source -limited setting s. Methods : We conducted a prospect i ve study of adherence in a pediatric HIV outpatient clinic in Cape Town , South Africa . Adherence was assessed by the Medication Event Monitoring System ( MEMS ) and caregiver self-report by Visual Analogue Scale ( VAS ) . Virologic response was recorded at study baseline and closest follow-up visit , child and caregiver data were collected by question naires . Results : For 73 children followed , median adherence by MEMS was 87.5 % ; median caregiver reported adherence was 100 % . MEMS and caregiver report differed in reporting excellent ( > 95 % ) adherence , with MEMS classifying 36 % of subjects in this category , whereas caregiver report classified 91 % . Overall , 65 % of children achieved virologic suppression after the study period . MEMS adherence was significantly associated with virologic suppression . The highest specificity was obtained when adjusting the data for doses taken at the prescribed time ( 91.3 % ) . No predictors for the differences between MEMS and caregiver reported adherence could be identified . Conclusions : Adherence to pediatric antiretroviral regimens in South Africa is not lower than in the developed world , yet not high enough to guarantee long-term treatment success . Caregiver report seems unreliable in this setting . MEMS is a feasible and accurate measure of adherence for children on liquid drug formulations Objectives Many question naires on adherence to antiretroviral therapy are in use , but the validity of patients ’ responses has not been tested . The Medication Adherence Self-Report Inventory ( MASRI ) has been developed and tested for its validity against objective measures and treatment outcome . Design Prospect i ve study comparing question naire responses with MEMS TrackCap ( MC , a medication event monitoring system ) , pill count ( PC ) and plasma HIV viraemia in a publicly funded specialist HIV clinic . Participants Patients self-medicating antiretroviral therapy who were not cognitively impaired and were able to read and underst and English . Results Mean adherence by MC of the 78 subjects was 92.9 % ( SE , 1.8 % ) and by PC 96.8 % ( SE , 1.4 % ) . Agreement between MC and responses to items about doses missed 1 , 2 or 3 days ago was low ( κ = 0.23 ( P < 0.03 ) , 0.44 ( P < 0.001 ) and 0.28 ( P < 0.01 ) respectively ) . This improved when these responses were summated ( κ = 0.46;P < 0.001 ) and was similar to that for recall of non-adherence over the preceding 2 weeks ( κ = 0.54;P < 0.001 ) . Mean self-reported adherence by visual analogue scale ( VAS ) over the preceding month was 93.3 % ( SE , 1.2 % ) . This was strongly associated with both MC ( r = 0.63;P < 0.001 ) and PC ( r = 0.75;P < 0.001 ) . On multivariate analysis , the strongest association between a MASRI item and MC was for the VAS . Both the 2 week recall and VAS items were inversely associated with viral load ( P = 0.01 ) . There was no association between dose timing ( measured MC or question naire ) or 3 day self-report and viral load . Conclusions The MASRI provides a means of measuring patient adherence that is valid when compared with objective measures Abstract The Center for Adherence Support Evaluation ( CASE ) Adherence Index , a simple composite measure of self-reported antiretroviral therapy ( ART ) adherence , was compared to a st and ard three-day self-reported adherence measure among participants in a longitudinal , prospect i ve cross-site evaluation of 12 adherence programs throughout the United States . The CASE Adherence Index , consisting of three unique adherence questions developed for the cross-site study , along with a three-day adherence self-report were administered by interviews every three months over a one-year period . Data from the three cross-site adherence questions ( individually and in combination ) were compared to three -day self-report data and HIV RNA and CD4 outcomes in cross-sectional analyses . The CASE Adherence Index correlated strongly with the three-day self-reported adherence data ( p<0.001 ) and was more strongly associated with HIV outcomes , including a 1-log decline in HIV RNA level ( maximum OR = 2.34 ; p<0.05 ) , HIV RNA < 400 copies/ml ( maximum OR = 2.33 ; p<0.05 ) and performed as well as the three-day self-report when predicting CD4 count status . Participants with a CASE Index score > 10 achieved a 98 cell mean increase in CD4 count over 12 months , compared to a 41 cell increase for those with scores ≤10 ( p<0.05 ) . The CASE Adherence Index is an easy to administer instrument that provides an alternative method for assessing ART adherence in clinical setting The aim of this study was to evaluate self-reporting of adherence to cardiovascular medication using electronic pillboxes ( medical event monitoring system [ MEMS ] ) as the gold st and ard comparator . In total , 78 individuals ( 52 % hypertensives , 21 % diabetics , 27 % with dyslipidemia ) were recruited prospect ively from an outpatient clinic setting in Switzerl and . Participants completed two self-report measures ( visual analogue scale [ VAS ] and a vali date d self-reporting question naire ) at baseline and were asked to use MEMS as their pillbox for the subsequent 10 weeks . Patients expressed their medication adherence behaviour on a VAS ( 0 mm=“I never take any tablets ” ; 100 mm=“I take all tablets as prescribed ” ) and entered one of six numbers ( from 1 : perfect adherence to 6 : non-adherence ) on the question naire . Medication compliance was monitored for 75 d on average . Mean ( ±SD , range ) scores for MEMS with respect to timing adherence , correct dosing , and self-administration adherence were 79±25 % ( 8–100 % ) , 83±20 % ( 24–100 % ) , and 92±17 % ( 54–118 % ) , respectively . A majority of participants ( 78.8 % ) over-reported their adherence to the VAS ( 93±7 mm , 73–100 ) , and VAS scores correlated poorly with MEMS recordings ( Spearman 's ρ for timing adherence , correct dosing , self-administration adherence 0.29 [ p=0.018 ] , 0.24 [ p=0.051 ] , 0.26 [ p=0.036 ] , respectively ) . Similarly , we found no correlation between adherence as expressed in the question naire and MEMS ( regression coefficients < 0.1 ) . We conclude that a majority of patients over-report adherence to cardiovascular medication if asked to complete a visual analogue scale and a vali date d question naire . Therefore , using self-reporting as the sole means of assessing medication compliance is insufficiently accurate to detect poor adherence BACKGROUND AND OBJECTIVE Clinicians often find it difficult to differentiate between subobtimal adherence and nonresponse to medical treatment if a patient 's clinical condition does not improve . This study aim ed to evaluate an adherence self-report tool to assess adherence to blood pressure lowering medication . STUDY DESIGN AND SETTING Participants were 245 patients with uncontrolled hypertension from 21 general practice s taking part in a r and omized trial . Prior to r and omization , participants were asked to indicate which of six descriptions ( adherence levels ) would most closely describe their medication taking and were given electronic medication monitors for 30 days . We used multivariable regression analysis to compare the adherence self-report tool with electronic monitoring . RESULTS There was strong evidence that a drop in one adherence level from level 1 ( highest level ) to level 2 and from level 2 to level 3 - 6 ( six being the lowest ) combined was associated with a decrease in timing compliance of approximately 5 % ( test for trend : P = 0.0004 ) . CONCLUSION Adherence assessed by a brief self-report tool was associated with timing compliance obtained through electronic monitoring in patients taking blood pressure lowering medication . Further research is required to investigate the validity of this tool in patients with lower adherence levels and in a nontrial population Context : Long‐term adherence to antiretrovirals is critical for sustained virologic response to HIV therapy in blood . Although antiretroviral therapy ( ART ) reduces HIV seminal shedding , little is known about the relationship between adherence to ART and HIV suppression in semen . Objective : To determine predictors of seminal HIV RNA suppression after 6 months of ART . Design : Prospect i ve observational cohort of 93 HIV‐infected subjects before and after introduction of ART . Seminal HIV RNA was measured at baseline and 1 , 2 , 3 , and 6 months after the introduction of therapy . Adherence to therapy was measured by self‐report . Setting : A large academic HIV reference center in Rio de Janeiro , Brazil . Main Outcome Measure : Detectable HIV RNA in semen . Results : In a multivariate logistic model with undetectable seminal HIV RNA after 6 months of therapy as the outcome variable , adjusting for baseline seminal viral load , both being adherent to therapy ( OR = 11.8 , P < 0.01 ) and using triple‐drug ART ( OR = 6.48 , P = 0.04 ) were independently associated with seminal HIV RNA suppression . Conclusions : Inability to adhere to therapy was strongly associated with persistent shedding of HIV RNA in semen . Measures to improve adherence are urgently needed to reduce the sexual spread of potentially drug‐resistant HIV among subjects using antiretrovirals UNLABELLED Background . Responsibility for medication can be an integral part of the informal caring role . Aims and objectives . To explore partnerships between older people and their carers in the management of medication and consider the implication s for health professionals . Methods . Older people and their carers were identified through community pharmacies in four r and omly selected areas of Engl and . Data regarding their activities , responsibilities and experiences of managing medication were collected in semi-structured interviews conducted in respondents ' own homes . Ninety-four transcripts relating to 47 older people and their associated carers were analysed using a qualitative approach . Results . Responsibility for medication was shared to varying extents between older people and their carers , and different patterns of partnership were identified . Differing perspectives between older people and their carers regarding the role , purpose and need for medication were revealed . Underlying these perspectives were issues concerning the sharing/concealment of information , autonomy and control . Caring was also described as a dynamic process . Older people and carers commented on how sharing responsibilities for medication varied on a day-to-day basis , as well as expressing concern regarding the changing needs of the older person and the carer 's capacity to cope . CONCLUSIONS Older people and their carers work together in diverse and sometimes complex ways to manage medication . Problems included dilemmas relating to the sharing of information , patient determination , disputes about the control of medication and concerns about the future . RELEVANCE TO PRACTICE These patterns of partnership need to be recognized and taken into account by health professionals when providing information , advice and support . They need to listen for indications of differing perspectives and be aware of their possible implication s for adherence to medication regimens . In caring for older people , health professionals need to find a balance that respects their autonomy whilst providing support for carers to enable them to be effective in their roles Background : The relationship between patient adherence and treatment outcomes has been documented across chronic health conditions , but the evidence base for effective adherence interventions in human immunodeficiency virus ( HIV ) and acquired immune deficiency syndrome ( AIDS ) requires more rigorous research and reporting . Objectives : The aims of this study were to determine whether a tailored , nurse-delivered adherence intervention program-Client Adherence Profiling and Intervention Tailoring (CAP-IT)-improved adherence to HIV medications , compared with st and ard care , and to identify the relationship among adherence measures . Methods : A r and omized controlled trial ( RCT ) with repeated measures was used to test the efficacy of CAP-IT over a 6-month period . A convenience sample of 240 participants was recruited from a freest and ing public HIV/AIDS clinic in Houston , TX , that provides medical , psychological , and pharmaceutical services for over 5,000 clients . Study instruments and measures included demographics ; chart audit to capture CD4 count , viral load , and prescribed medications ; health literacy ; and five measures of adherence ( AIDS Clinical Trial Group-Revised Reasons for Missing Medications , Morisky Self-Report of Medication Non-Adherence , Pill Count , Medication Event Monitoring System [ MEMS ] caps , and Pharmacy Refill ) . Results : A logistic regression using generalized estimating equations method showed no significant differences over time on the five medication-adherence measures between the experimental and control groups . Little correlation was documented among the five different adherence measures , and there was minimal correlation with clinical markers . Discussion : It is unclear why the tailored adherence intervention was not efficacious in improving medication adherence . The findings suggest that these measures of medication adherence did not perform as expected and that , perhaps , they are not adequate measures of adherence . Effective and efficient adherence interventions are needed to address the barriers to medication adherence in HIV/AIDS We prospect ively studied long-term antiretroviral adherence patterns and their impact on biologic outcomes for human immunodeficiency virus (HIV)-infected participants in 2 r and omized , multicenter clinical trials . For the period from baseline to month 12 of the study , participants who reported adherence levels of 100 % , 80%-99 % , and 0%-79 % had plasma HIV RNA levels that decreased by 2.77 , 2.33 , and 0.67 log(10 ) copies/mL , respectively ( P<.001 ) , whereas their CD4 counts increased by 179 , 159 , and 53 cells/mm(3 ) , respectively ( P<.001 ) . Adherence predicted nondetectable HIV RNA levels ( < 50 copies/mL ) at 12 months of follow-up ( P<.001 ) . The HIV RNA level was nondetectable in 72 % of participants who reported 100 % adherence at all 4 follow-up visits , compared with 66 % , 41 % , 35 % , and 13 % of participants who reported 100 % adherence at 3 , 2 , 1 , or 0 follow-up visits , respectively ( P<.001 ) . Nonwhite race was associated with poorer adherence ( P<.001 ) , and older age was associated with better adherence ( P<.001 ) Objective : Self-report of antiretroviral medications adherence is inexpensive and simple to use in clinical setting s but grossly overestimates adherence . We investigated methods to calibrate patients ' self-reported adherence to match objective ly measured adherence more closely for the purpose of developing a practical and more accurate self-reported adherence measure . Design : Longitudinal cohort design . Methods : Using data from 2 prospect i ve longitudinal clinical investigations conducted at 5 HIV clinics , we examined the discrepancy between self-reported adherence and objective ly measured adherence . We evaluated the relation between attitudinal measures and the degree of discrepancy and used a cross-validation approach to propose c and i date items to improve adherence survey methodology . Results : Among 330 patients , self-reported adherence was consistently higher than objective ly measured adherence . The best calibration models included the patient 's self-reported adherence , duration of the antiretroviral regimen , and attitudinal measures ( ability to take medication as instructed , believing medication can help one to live longer , whether or not it is too troublesome to take antiretrovirals , and feeling things are going the right way ) . Conclusion : The method efficiently identified survey items to improve self-reported adherence measurement . The calibrated measure more closely approximates objective ly measured adherence and is more sensitive for detecting nonadherence . These models merit evaluation in other setting Objective To assess the effectiveness of the simplified medication adherence question naire ( SMAQ ) in identifying non-adherent patients . Design Prospect i ve observational study of adherence . The six-item SMAQ was developed . The following aspects were evaluated : ( i ) criterion validity , comparison with electronic adherence monitoring ; ( ii ) construct validity , association between adherence , as defined by the SMAQ , and virological outcomes ; and ( iii ) reliability , internal consistency and reproducibility . Patients A group of 3004 unselected HIV patients who had initiated nelfinavir therapy combined with other antiretroviral drugs [ 21 % naive , 15 % protease inhibitor (PI)-naive , 64 % PI-experienced ] between January 1998 and December 1999 were enrolled in 69 hospitals in Spain . The SMAQ was administered at months 3 , 6 and 12 . Results The SMAQ showed 72 % sensitivity , 91 % specificity and a likelihood ratio of 7.94 to identified non-adherent patients , compared with the medication-event monitoring system ( 40 patients evaluated ) . At month 12 , 1797 patients were evaluated , of whom 32.3 % were defined as non-adherent ; viral load < 500 copies/ml found in 68.3 % of the adherent , and 46 % of the non-adherent patients . A logistic regression analysis of PI-naive patients was performed , including age , sex , baseline viral load > 5 log10/ml , CD4 cell count < 200 × 106/l , and non-adherence as independent variables . Non-adherence was the only significant risk factor in failing to achieve virological suppression . Cronbach 's alpha internal consistency coefficient was 0.75 , and overall inter-observer agreement was 88.2 % . Conclusion The SMAQ appears to be an adequate instrument with which to assess adherence in HIV-infected patients , and may be applied in most clinical setting Abstract A r and omised trial compared two instruments for assessing self-reported adherence to antiretroviral medications : ( 1 ) a day-by-day recall instrument that elicited the number of missed doses in each of the prior three days ( 3-day instrument ; n=64 ) and ( 2 ) a general recall instrument that elicited an estimate of proportion of pills taken during the prior seven days ( 7-day instrument ; n=70 ) . Adherence was measured at study visits over 12 months among participants in a clinical trial assessing treatment strategies for individuals with virologic failure and multidrug-resistant HIV . Participants had a median ( interquartile range ) of 133 ( 41–264 ) CD4 cells/ml3 and a median of 10 major HIV resistance mutations at baseline . Mean adherence levels were 90–98 % throughout the study . There was a greater trend in the likelihood of 100 % adherence when measured by the 3-day versus the 7-day instrument ( odds ratio (OR)=1.45 ; p=0.06 ) . The likelihood of consistent 100 % adherence measured by either instrument decreased over time ( p<0.001 ) . Participants reporting 100 % adherence at more than half of study visits had better virologic and immunologic outcomes at month-12 compared to those reporting 100 % adherence at half or fewer visits ( HIV RNA decline of 0.96 versus 0.51 log , respectively , p=0.02 ; and CD4 cell increase of 51.0 versus 17.8 cells , p=0.04 ) . This study demonstrated the utility of the general 7-day recall adherence self-report instrument as well as the 3-day day-by-day recall adherence self-report instrument for measuring antiretroviral adherence . Self-reported adherence was significantly associated with virologic and immunologic outcomes in this population with advanced drug-resistant HIV disease |
1,236 | 25,711,728 | Conclusions Antenatal PFMT might be effective at shortening the first and second stage of labor in the primigravida .
Antenatal PFMT may not increase the risk of episiotomy , instrumental delivery , and perineal laceration in the primigravida | Introduction and hypothesisPelvic floor muscle training ( PFMT ) has been widely used to prevent and treat urinary incontinence ; however , the possible effect of antenatal PFMT on labor and delivery is still not clear .
The purpose of the study was to investigate the possible effect of antenatal PFMT on labor and delivery . | It is thought that antenatal pelvic floor muscle training ( PFMT ) might produce a strong pelvic floor result ing in prolonged labour , whilst some believe it produces well-controlled muscles that facilitate rotation of the foetal head and shortens the duration of labour . This secondary analysis ( of a previously published r and omised controlled trial ) assesses the labour and delivery details of 268 primigravidae who were originally r and omised at approximately 20 weeks gestation to supervised PFMT or a control group . Between the two groups , there was no difference in the duration of the second stage of labour or in the need for instrumental delivery . PFMT does not appear to facilitate or obstruct labour Epidemiological studies have postulated racial differences in the incidence and prevalence of pelvic floor disorders . There are anecdotal data from cadaver dissections suggesting that Asian women benefit from stronger pelvic support structures . A prospect i ve observational clinical study was conducted in order to test for differences in pelvic organ support in 200 nulliparous pregnant women . Assessment included translabial ultrasound , documenting the position of the pelvic organs and mobility on Valsalva relative to the inferoposterior symphyseal margin . The largest ethnic groups were Asian ( n=16 ) and Caucasian women ( n=161 ) . On comparing the groups , both antepartum and postpartum analyses showed significantly less pelvic organ mobility in Asians . This was true for virtually all parameters of organ mobility and both anterior ( P=0.002 antepartum , P=0.009 postpartum ) and posterior compartments ( P=0.04 antepartum , P=0.02 postpartum ) . No significant differences were detected for cervical mobility . It was concluded that Asian women seem to show less mobility of the anterior and posterior vaginal compartments than Caucasians OBJECTIVE : This study aim ed to compare the pelvic floor muscle strength of nulliparous and primiparous women . METHODS : A total of 100 women were prospect ively distributed into two groups : Group 1 ( G1 ) ( n = 50 ) included healthy nulliparous women , and Group 2 ( G2 ) ( n = 50 ) included healthy primiparous women . Pelvic floor muscle strength was subjectively evaluated using transvaginal digital palpation . Pelvic floor muscle strength was objective ly assessed using a portable perineometer . All of the parameters were evaluated simultaneously in G1 and were evaluated in G2 during the 20th and 36th weeks of pregnancy and 45 days after delivery . RESULTS : In G2 , 14 women were excluded because they left the study before the follow-up evaluation . The median age was 23 years in G1 and 22 years in G2 ; there was no significant difference between the groups . The average body mass index was 21.7 kg/m2 in G1 and 25.0 kg/m2 in G2 ; there was a significant difference between the groups ( p = 0.0004 ) . In G2 , transvaginal digital palpation evaluation showed significant impairments of pelvic floor muscle strength at the 36th week of pregnancy ( p = 0.0006 ) and 45 days after vaginal delivery ( p = 0.0001 ) compared to G1 . Objective evaluations of pelvic floor muscle strength in G2 revealed a significant decrease 45 days after vaginal delivery compared to nulliparous patients . CONCLUSION : Pregnancy and vaginal delivery may cause weakness of the pelvic floor muscles OBJECTIVE Urinary incontinence is a chronic health complaint that severely reduces quality of life . Pregnancy and vaginal delivery are main risk factors in the development of urinary incontinence . The aim of this study was to assess whether intensive pelvic floor muscle training during pregnancy could prevent urinary incontinence . METHODS We conducted a single-blind r and omized controlled trial at Trondheim University Hospital and three outpatient physiotherapy clinics in a primary care setting . Three hundred one healthy nulliparous women were r and omly allocated to a training ( n = 148 ) or a control group ( n = 153 ) . The training group attended a 12-week intensive pelvic floor muscle training program during pregnancy , supervised by physiotherapists . The control group received the customary information . The primary outcome measure was self-reported symptoms of urinary incontinence . The secondary outcome measure was pelvic floor muscle strength . RESULTS At follow-up , significantly fewer women in the training group reported urinary incontinence : 48 of 148 ( 32 % ) versus 74 of 153 ( 48 % ) at 36 weeks ' pregnancy ( P = .007 ) and 29 of 148 ( 20 % ) versus 49 of 153 ( 32 % ) 3 months after delivery ( P = .018 ) . According to numbers needed to treat , intensive pelvic floor muscle training during pregnancy prevented urinary incontinence in about one in six women during pregnancy and one in eight women after delivery . Pelvic floor muscle strength was significantly higher in the training group at 36 weeks ' pregnancy ( P = .008 ) and 3 months after delivery ( P = .048 ) . CONCLUSION Intensive pelvic floor muscle training during pregnancy prevents urinary incontinence during pregnancy and after delivery . Pelvic floor muscle strength improved significantly after intensive pelvic floor muscle training Abstract Objective : To compare the effect of pelvic floor exercises , electrical stimulation , vaginal cones , and no treatment for genuine stress incontinence . Design : Stratified , single blind , r and omised controlled trial . Setting : Multicentre . Participants : 107 women with clinical ly and urodynamically proved genuine stress incontinence . Mean ( range ) age was 49.5 ( 24 - 70 ) years , and mean ( range ) duration of symptoms 10.8 ( 1 - 45 ) years . Interventions : Pelvic floor exercise ( n=25 ) comprised 8 - 12 contractions 3 times a day and exercise in groups with skilled physical therapists once a week . The electrical stimulation group ( n=25 ) used vaginal intermittent stimulation with the MS 106 Twin at 50 Hz 30 minutes a day . The vaginal cones group ( n=27 ) used cones for 20 minutes a day . The untreated control group ( n=30 ) was offered the use of a continence guard . Muscle strength was measured by vaginal squeeze pressure once a month . Main outcome measures : Pad test with st and ardised bladder volume , and self report of severity . Results : Improvement in muscle strength was significantly greater ( P=0.03 ) after pelvic floor exercises ( 11.0 cm H2O ( 95 % confidence interval 7.7 to 14.3 ) before v 19.2 cm H2O ( 15.3 to 23.1 ) after ) than either electrical stimulation ( 14.8 cm H2O ( 10.9 to 18.7 ) v 18.6 cm H2O ( 13.3 to 23.9 ) ) or vaginal cones ( 11.8 cm H2O ( 8.5 to 15.1 ) v 15.4 cm H2O ( 11.1 to 19.7 ) ) . Reduction in leakage on pad test was greater in the exercise group ( −30.2 g ; −43.3 to 16.9 ) than in the electrical stimulation group ( −7.4 g ; −20.9 to 6.1 ) and the vaginal cones group ( −14.7 g ; −27.6 to −1.8 ) . On completion of the trial one participant in the control group , 14 in the pelvic floor exercise group , three in the electrical stimulation group , and two in the vaginal cones group no longer considered themselves as having a problem . Conclusion : Training of the pelvic floor muscles is superior to electrical stimulation and vaginal cones in the treatment of genuine stress incontinence OBJECTIVE Prospect i ve study to objective ly evaluate the benefits of pelvic floor strengthening exercises associated to biofeedback for the treatment of stress urinary incontinence . MATERIAL S AND METHODS Fourteen patients diagnosed with stress urinary incontinence ( SUI ) were selected for this study . All patients underwent a pelvic floor training associated to biofeedback for 12 consecutive weeks . Urodynamic tests , pad test and bladder diary were analyzed at the beginning of the study , at the end and after 3 months . The King 's Health Question naire ( KHQ ) was applied before and after treatment to assess the impact in the quality of life . RESULTS There was a significant reduction in the pad weight ( from 14.21 g to 1 g ) , number of urinary leakage episodes ( from 8.14 per day to 2.57 per day ) and daytime frequency ( from 7.93 per day to 5.85 per day ) . At urodynamics the authors observed a significant increase in Valsalva leak-point pressure ( from 103.93 cm H2O to 139.14 cm H2O ) , cistometric capacity ( from 249.29 mL to 336.43 mL , p = 0.0015 ) and bladder volume at first desire to void ( from 145 mL to 215.71 mL ) . Those differences were kept during the first 3 months of follow up . The KHQ revealed significant differences except in the case of ' ' general health perception ' ' , which covers health in general and not exclusively urinary incontinence . CONCLUSION Treatment of SUI with pelvic floor exercises associated to biofeedback caused significant changes in the parameters analyzed , with maintenance of good results 3 months after treatment AIM This article is a report of a study of the effects of a pelvic floor muscle exercise programme on the severity of stress urinary incontinence in pregnant women . BACKGROUND Pregnancy is main risk factor for the development of stress urinary incontinence . Stress urinary incontinence can be cured by pelvic floor muscle exercise which is a safe inexpensive treatment with no complications and does not require the use of instruments . METHODOLOGY A quasi-experimental study , pre-post test with control group design was used at the antenatal care unit in a tertiary care hospital between June and October of 2006 . The participants were 66 pregnant women who had stress urinary incontinence with gestational ages of 20 - 30 weeks . The main outcome measure was severity of stress urinary incontinence which comprised frequency and amount of urine leakage and perceived severity of stress urinary incontinence . RESULTS After the experimental group 's participation in the pelvic floor muscle exercise programme , the frequency and amount of urine leakage and the score of perceived stress urinary incontinence severity were significantly lower than the same scores before participation in the programme . In addition , women in the experimental group had frequency and volume of urine leakage , and score of perceived stress urinary incontinence severity after participation significantly lower than those in the control group . CONCLUSION The 6-week pelvic floor muscle exercise programme was able to decrease the severity of symptoms in pregnant women with stress urinary incontinence Introduction and hypothesisThe aim of the study was to evaluate the effect of antenatal pelvic floor muscle exercise ( PFME ) in the prevention and treatment of urinary incontinence during pregnancy and postpartum period . Methods Three hundred women were r and omly assigned to the PFME group and control group . Urinary symptoms were measured by Urogenital Distress Inventory-6 ( UDI-6 ) , Incontinence Impact Question naire-7 ( IIQ-7 ) , and question of self-reported urinary incontinence . Question naire scores of the PFME and the control groups were compared and analyzed . Results During late pregnancy and the postpartum period , the PFME group had significantly lower total UDI-6 and IIQ-7 scores ; their self-report rate of urinary incontinence was also less than the control group . Additionally , we found whether in PFME or control , women who delivered vaginally were more likely to develop postpartum urinary leakage than women who delivered by cesarean section . Conclusions PFME applied in pregnancy is effective in the treatment and prevention of urinary incontinence during pregnancy , and this effect may persist to postpartum period Please cite this paper as : Stafne S , Salvesen K , Romundstad P , Torjusen I , Mørkved S. Does regular exercise including pelvic floor muscle training prevent urinary and anal incontinence during pregnancy ? A r and omised controlled trial . BJOG 2012;119:1270–1280 Introduction and hypothesisTheoretically , tight or strong pelvic floor muscles may impair the progress of labor and lead to instrumental deliveries . We aim ed to investigate whether vaginal resting pressure , pelvic floor muscle strength , or endurance at midpregnancy affect delivery outcome . Methods This was a prospect i ve cohort study of women giving birth at a university hospital . Vaginal resting pressure , pelvic floor muscle strength , and endurance in 300 nulliparous pregnant women were assessed at mean gestational week 20.8 ( ±1.4 ) using a high precision pressure transducer connected to a vaginal balloon . Delivery outcome measures [ acute cesarean section , prolonged second stage of labor ( > 2 h ) , instrumental vaginal delivery ( vacuum and forceps ) , episiotomy , and third- and fourth-degree perineal tear ) were retrieved from the hospital ’s electronic birth records . Results Twenty-three women were lost to follow-up , mostly because they gave birth at another hospital . Women with prolonged second stage had significantly higher resting pressure than women with second stage less than 2 h ; the mean difference was 4.4 cmH2O [ 95 % confidence interval ( CI ) 1.2–7.6 ] , p < 0.01 , adjusted odds ratio 1.049 ( 95 % CI 1.011–1.089 , p = 0.012 ) . Vaginal resting pressure did not affect other delivery outcomes . Pelvic floor muscle strength and endurance similarly were not associated with any delivery outcomes . Conclusions While midpregnancy vaginal resting pressure is associated with prolonged second stage of labor , neither vaginal resting pressure nor pelvic floor muscle strength or endurance are associated with operative delivery or perineal tears . Strong pelvic floor muscles are not disadvantageous for vaginal delivery AIM This article reports a r and omised controlled trial to determine the efficacy of antenatal pelvic floor muscle exercises in the primary prevention of postpartum stress incontinence in primiparous women . BACKGROUND Pelvic floor muscle exercises are effective in treating stress incontinence , yet prevention studies demonstrate equivocal findings . DESIGN R and omised controlled trial . METHOD Pregnant women recruited from two hospitals in North-west Engl and were r and omised to an intervention ( n = 141 ) or control group ( n = 145 ) . Data were collected from 2005 - 2006 . The intervention comprised four sessions of taught pelvic floor muscle exercise training during pregnancy and 8 - 12 maximal contractions repeated twice daily at home . A modified Bristol Female Lower Urinary Tract Symptom question naire , Leicester Impact Scale and Three Day Diary were administered at 20 and 36 weeks of pregnancy and three months postpartum . RESULTS The intervention group was more likely to exercise their pelvic floor muscles compared to controls at 36 weeks ( p = 0.019 ) and three months ( 0.022 ) , reporting fewer episodes of incontinence and a lower score on the Leicester Impact Scale . However , these differences were not statistically significant . CONCLUSION Significant differences were not demonstrated between the groups in relation to incontinence episodes and degree of bother of symptoms postpartum , although trends indicate a positive effect . Further research is necessary to address issues of adherence and the effect of pelvic floor muscle exercise undertaken during pregnancy on postpartum stress urinary incontinence . RELEVANCE TO CLINICAL PRACTICE A proportion of women did not meet the required attendance at antenatal class , furthermore , few exercised their pelvic floor muscles during pregnancy according to instructions . Health professionals need to find ways to instruct and motivate women to perform pelvic floor muscles exercises regularly during pregnancy and the postpartum Abstract Objectives To examine a possible effect on labour of training the muscles of the pelvic floor during pregnancy . Design R and omised controlled trial . Setting Trondheim University Hospital and three outpatient physiotherapy clinics in a primary care setting . Participants 301 healthy nulliparous women r and omly allocated to a training group ( 148 ) or a control group ( 153 ) . Intervention A structured training programme with exercises for the pelvic floor muscles between the 20th and 36th week of pregnancy . Main outcome measures Duration of the second stage of labour and number of deliveries lasting longer than 60 minutes of active pushing among women with spontaneous start of labour after 37 weeks of pregnancy with a singleton fetus in cephalic position . Results Women r and omised to pelvic floor muscle training had a lower rate of prolonged second stage labour ( 24 % , 95 % confidence interval 16 % to 33 % ; 22 out of 105 women were at risk ( undelivered ) at 60 minutes in the survival analysis ) than women allocated to no training ( 38 % ( 37/109 ) , 28 % to 47 % ) . The duration of the second stage was not significantly shorter ( 40 minutes v 45 minutes , P = 0 . 06 ) . Conclusions A structured training programme for the pelvic floor muscles is associated with fewer cases of active pushing in the second stage of labour lasting longer than 60 minutes |
1,237 | 20,492,638 | Conclusions Tai Chi appears to be associated with improvements in psychological well-being including reduced stress , anxiety , depression and mood disturbance , and increased self-esteem . | Background Physical activity and exercise appear to improve psychological health .
However , the quantitative effects of Tai Chi on psychological well-being have rarely been examined . | Tai Chi , a moving meditation , is examined for its efficacy in post-stressor recovery . Forty-eight male and 48 female Tai Chi practitioners were r and omly assigned to four treatment groups : Tai Chi , brisk walking , mediation and neutral reading . Mental arithmetic and other difficult tests were chosen as mental challenges , and a stressful film was used to produce emotional disturbance . Tai Chi and the other treatments were applied after these stressors . After all treatments , the salivary cortisol level dropped significantly , and the mood states were also improved . In general the stress-reduction effect of Tai Chi characterized moderate physical exercise . Heart rate , blood pressure , and urinary catecholamine changes for Tai Chi were found to be similar to those for walking at a speed of 6 km/hr . Although Tai Chi appeared to be superior to neutral reading in the reduction of state anxiety and the enhancement of vigour , this effect could be partially accounted for by the subjects ' high expectations about gains from Tai Chi . Approaches controlling for expectancy level are recommended for further assessment Psychoneuroimmunology is a framework for mind-body practice and research that combines cutting-edge scientific exploration with holistic philosophy to appreciate and underst and stress responses . The rapidly growing research literature provides a foundation for building an integrative stress management model with the potential to positively influence the stress-disease relationship and , ultimately , health outcomes . This article introduces a novel tai chi intervention and provides quantitative and qualitative data from a r and omized clinical trial indicating its effects on psychosocial variables in individuals living with various stages of HIV disease BACKGROUND Stress can affect health . There is a growing need for the evaluation and application of professional stress management options , i.e , stress reduction . Mind/body medicine serves this goal , e.g , by integrating self-care techniques into medicine and health care . Tai Chi ( TC ) can be classified as such a mind/body technique , potentially reducing stress and affecting physical as well as mental health parameters , which , however , has to be examined further . MATERIAL / METHODS We conducted a prospect i ve , longitudinal pilot study over 18 weeks for the evaluation of subjective and objective clinical effects of a Yang style TC intervention in young adults ( beginners ) by measuring physiological ( blood pressure , heart rate , saliva cortisol ) and psychological ( SF-36 , perceived stress , significant events ) parameters , i.e , direct or indirect indicators of stress and stress reduction , in a non-r and omised/-controlled , yet non-selected cohort ( n=21 ) by pre-to-post comparison and in follow-up . SF-36 values were also compared with the age-adjusted norm population , serving as an external control . Additionally , we measured diurnal cortisol profiles in a cross-sectional sub- study ( n=2 + 2 , pre-to-post ) , providing an internal r and om control sub- sample . RESULTS Only nine participants completed all measurements . Even so , we found significant ( p<0.05 ) reductions of saliva cortisol ( post and follow-up ) , which seems to be an indicator of general stress reduction . A significant decrease in perceived mental stress ( post ) proved even highly significant ( p<0.01 ) in the follow-up , whereas physical stress perception declined to a much lesser degree . Significant improvements were also detected for the SF-36 dimensions general health perception , social functioning , vitality , and mental health/psychological well-being . Thus , the summarized mental health measures all clearly improved , pointing towards a predominantly psychological impact of TC . CONCLUSIONS Subjective health increased , stress decreased ( objective ly and subjectively ) during TC practice . Future studies should confirm this observation by rigorous methodology and by further combining physical and psychological measurements with basic research , thereby also gaining knowledge of autoregulation and molecular physiology that possibly underlies mind/body medicine Abstract Anxiety sensitivity , or the belief that anxiety-related sensations can have negative consequences , has been shown to play an important role in the etiology and maintenance of panic disorder and other anxiety-related pathology . Aerobic exercise involves exposure to physiological cues similar to those experienced during anxiety reactions . The present study sought to investigate the efficacy of a brief aerobic exercise intervention for high anxiety sensitivity . Accordingly , 24 participants with high anxiety sensitivity scores ( Anxiety Sensitivity Index-Revised scores > 28 ) were r and omly assigned to complete either six 20-minute sessions of aerobic exercise or a no-exercise control condition . The results indicated that individuals assigned to the aerobic exercise condition reported significantly less anxiety sensitivity subsequent to exercise , whereas anxiety sensitivity scores among non-exercisers did not significantly change . The clinical research and public health implication s of these findings are discussed , and several potential directions for additional research are recommended Objective : Alternative approaches to weight control and physical activity are increasingly needed . Numerous factors influence weight management , including the choice of physical exercise . No study has previously examined the therapeutic effect of a multidisciplinary weight management program incorporating Tai Chi ( TC ) exercises among sedentary obese women . Design : R and omized intervention trial with blinded medical provider . Setting : In day hospital consultations . Participants : Twenty-one obese women . Intervention : All subjects participated in a 10-week weight management program that was part of usual care and included a hypocaloric balanced diet , a weekly physician/psychologist/dietician group session , and an exercise program . For the exercise component , subjects were r and omized to either a 2-hour weekly session of TC or a conventional structured exercise program . Main Outcome Measures : Changes in weight , body composition , heart rate , blood pressure , mobility scores , mood , Three Factor Eating Question naire scores , and General Self-Efficacy . Results : The TC arm improved in resting systolic blood pressure , chair rise test , mood , and reduced percent of fat at week 10 and at 6 months follow-up . General self-efficacy was enhanced in both groups and maintained at 30 weeks . Conclusion : The observed benefits over a 30-week period of a multidisciplinary weight management program incorporating TC exercises on physical functioning mood and dietary restraint need further underst and ing of how sedentary obese women adhere to physical activity like TC or other alternative exercises Older persons who are willing to begin exercise programs are often not willing to continue them . At the Atlanta FICSIT ( Frailty and Injuries : Cooperative Studies of Intervention Techniques ) site , individuals aged 70 + were r and omized to Tai Chi ( TC ) , individualized balance training ( BT ) , and exercise control education ( ED ) groups for 15 weeks . In a follow-up assessment 4 months post-intervention , 130 subjects responded to exit interview questions asking about perceived benefits of participation . Both TC and BT subjects reported increased confidence in balance and movement , but only TC subjects reported that their daily activities and their overall life had been affected ; many of these subjects had changed their normal physical activity to incorporate ongoing TC practice . The data suggest that when mental as well as physical control is perceived to be enhanced , with a generalized sense of improvement in overall well-being , older persons ' motivation to continue exercising also increases Goals Health-related quality of life ( HRQL ) and self-esteem are often diminished among women diagnosed and treated for breast cancer . Tai Chi is a moderate form of exercise that may be an effective therapy for improving HRQL and self-esteem among these women . We sought to compare the efficacy of Tai Chi Chuan ( TCC ) and psychosocial support ( PST ) for improving HRQL and self-esteem among breast cancer survivors . Patients and methods A group of 21 women diagnosed with breast cancer , who had completed treatment within the last 30 months were r and omized to receive 12 weeks of TCC or PST . Participants in both groups met three times a week for 60 minutes . HRQL and self-esteem were assessed at baseline , 6 weeks , and 12 weeks . Results The TCC group demonstrated significant improvements in HRQL , while the PST group reported declines in HRQL , with the differences between the two groups approaching significance at week 12 . Additionally , the TCC group exhibited improvements in self-esteem , while the PST group reported declines in self-esteem , with the differences between groups reaching statistical significance at week 12 . These findings , coupled with a visual inspection of the raw change scores , support the plausibility of a dose-response relationship concerning Tai Chi . Conclusions In this pilot investigation , the TCC group exhibited improvements in HRQL and self-esteem from baseline to 6 and 12 weeks , while the support group exhibited declines . R and omized , controlled clinical trials with larger sample sizes are needed AIM This paper reports a study to examine change in psychosocial status following a 12-week Tai Chi exercise intervention among ethnic Chinese people with cardiovascular disease risk factors living in the United States of America . BACKGROUND Regular participation in physical activity is associated with protection against cardioavascular disease , and improvements in physical and psychological health . Increasing amounts of scientific evidence suggests that mind-body exercise , such as Tai Chi , are related to improvements in mental health , emotional well-being , and stress reduction . No prior study has examined the effect of a Tai Chi exercise intervention on psychosocial status among people with cardiovascular disease risk factors . METHODS This was a quasi-experimental study . Participants attended a 60-minute Tai Chi exercise class three times per week for 12 weeks . Data were collected at baseline , 6 and 12 weeks following the intervention . Psychosocial status was assessed using Chinese versions of Cohen 's Perceived Stress Scale , Profile of Mood States , Multidimensional Scale of Perceived Social Support , and Tai Chi exercise self-efficacy . RESULTS A total of 39 participants , on average 66-year-old ( + /-8.3 ) , married ( 85 % ) , Cantonese-speaking ( 97 % ) , immigrants participated . The majority were women ( 69 % ) , with < or = 12 years education ( 87 % ) . Statistically significant improvements in all measures of psychosocial status were found ( P < or = 0.05 ) following the intervention . Improvement in mood state ( eta2 = 0.12 ) , and reduction in perceived stress ( eta2 = 0.13 ) were found . In addition , Tai Chi exercise statistically significantly increased self-efficacy to overcome barriers to Tai Chi ( eta2 = 0.19 ) , confidence to perform Tai Chi ( eta2 = 0.27 ) , and perceived social support ( eta2 = 0.12 ) . CONCLUSIONS Tai Chi was a culturally appropriate mind-body exercise for these older adults , with statistically significant psychosocial benefits observed over 12-weeks . Further research examining Tai Chi exercise using a r and omized clinical trial design with an attention-control group may reduce potential confounding effects , while exploring potential mechanisms underlying the relaxation response associated with mind-body exercise . In addition , future studies with people with other chronic illnesses in all ethnic groups are recommended to determine if similar benefits can be achieved OBJECTIVES To determine whether an intense tai chi exercise program could reduce fear of falling better than a wellness education ( WE ) program in older adults who had fallen previously and meet criteria for transitioning to frailty . DESIGN Cluster-r and omized , controlled trial of 48 weeks ' duration . SETTING Ten matched pairs of congregate living facilities in the greater Atlanta area . PARTICIPANTS Sample of 291 women and 20 men , aged 70 to 97 . MEASUREMENTS Activity-related fear of falling using the Activities-Specific Balance Confidence Scale ( ABC ) and the Fall Efficacy Scale at baseline and every 4 months for 1 year . Demographics , time to first fall and all subsequent falls , functional measures , Centers for Epidemiologic Studies Depression Scale , medication use , level of physical activity , comorbidities , and adherence to interventions . RESULTS Mean ABC was similar in both cohort groups at the time of r and omization but became significantly higher ( decreased fear ) in the tai chi cohort at 8 months ( 57.9 vs 49.0 , P<.001 ) and at study end ( 59.2 vs 47.9 , P<.001 ) . After adjusting for covariates , the mean ABC after 12 months of intervention was significantly greater in the tai chi group than in the WE group , with the differences increasing with time ( mean difference at 12 months=9.5 points , 95 % confidence interval=4.8 - 14.2 , P<.001 ) . CONCLUSION Tai chi led to a significantly greater reduction in fear of falling than a WE program in transitionally frail older adults . The mean percentage change in ABC scores widened between tai chi and WE participants over the trial period . Tai chi should be considered in any program design ed to reduce falling and fear of falling in transitionally frail older adults Background Fibromyalgia ( FM ) , one of the most common musculoskeletal disorders , is associated with high levels of impaired health and inadequate or limited symptom relief . The cause of this complex syndrome is unknown , and there is no known cure . Numerous research results indicate that a combination of physical exercise and mind-body therapy is effective in symptom management . T’ai Chi , an ancient Chinese exercise , combines physical exercise with mind-body therapy . Purpose To investigate the effects of T’ai Chi exercise on FM symptoms and health-related quality of life . Design Pilot study , one group pre-to-post posttest design . Methods Participants with FM ( n = 39 ) formed a single group for 6 weeks of 1-hour , twice weekly T’ai Chi exercise classes . FM symptoms and health-related quality of life were measured before and after exercise . Findings Twenty-one participants completed at least 10 of the 12 exercise sessions . Although the dropout rate was higher than expected , measurements on both the Fibromyalgia Impact Question naire ( FIQ ) ( Buckhardt , Clark , & Bennett , 1991 ) and the Short Form-36 ( SF-36 ) ( Ware & Sherbourne , 1992 ) revealed statistically significant improvement in symptom management and health-related quality of life . Implication s for Nursing Research Knowledge of interventions to enhance health for the patient with musculoskeletal problems is a National Association of Orthopaedic Nurses priority . T’ai Chi is potentially beneficial to patients with FM . Further research is needed to support evidence -based practice OBJECTIVES To evaluate the effects on blood pressure , lipid profile , and anxiety status on subjects received a 12-week Tai Chi Chuan exercise program . DESIGN R and omized controlled study of a Tai Chi Chuan group and a group of sedentary life controls . SETTING Taipei Medical University Hospitals and University campus in the Taipei , Taiwan , area . SUBJECTS Two ( 2 ) selected groups of 76 healthy subjects with blood pressure at high-normal or stage I hypertension . INTERVENTION A 12-week Tai Chi Chuan exercise training program was practice d regularly with a frequency of 3 times per week . Each session included 10-minute warm-up , 30-minute Tai Chi exercise , 10-minute cool-down . Exercise intensity was estimated to be approximately 64 % of maximal heart rate . OUTCOME MEASURES Blood pressure , lipid profile and anxiety status ( State-Trait Anxiety Inventory ; STAI ) were evaluated . RESULTS After 12-weeks of Tai Chi training , the treatment group showed significant decrease in systolic blood pressure of 15.6 mm Hg and diastolic blood pressure 8.8 mm Hg . The serum total cholesterol level decreased 15.2 mg/dL and high-density lipoprotein cholesterol increased 4.7 mg/dL. By using STAI evaluation , both trait anxiety and state anxiety were decreased . CONCLUSIONS This study shows that under well- design ed conditions , Tai Chi exercise training could decrease blood pressure and results in favorable lipid profile changes and improve subjects ' anxiety status . Therefore , Tai Chi could be used as an alternative modality in treating patients with mild hypertension , with a promising economic effect OBJECTIVES To evaluate the effects of a behavioral intervention , Tai Chi , on resting and vaccine-stimulated levels of cell-mediated immunity ( CMI ) to varicella zoster virus ( VZV ) and on health functioning in older adults . DESIGN A prospect i ve , r and omized , controlled trial with allocation to two arms ( Tai Chi and health education ) for 25 weeks . After 16 weeks of intervention , subjects were vaccinated with VARIVAX , the live attenuated Oka/Merck VZV vaccine licensed to prevent varicella . SETTING Two urban U.S. communities between 2001 and 2005 . PARTICIPANTS A total of 112 healthy older adults aged 59 to 86 . MEASUREMENTS The primary endpoint was a quantitative measure of VZV-CMI . Secondary outcomes were scores on the Medical Outcomes Study 36-item Short-Form Health Survey ( SF-36 ) . RESULTS The Tai Chi group showed higher levels of VZV-CMI than the health education group ( P<.05 ) , with a significant rate of increase ( P<.001 ) that was nearly twice that found in the health education group . Tai Chi alone induced an increase in VZV-CMI that was comparable in magnitude with that induced by varicella vaccine , and the two were additive ; Tai Chi , together with vaccine , produced a substantially higher level of VZV-CMI than vaccine alone . The Tai Chi group also showed significant improvements in SF-36 scores for physical functioning , bodily pain , vitality , and mental health ( P<.05 ) . CONCLUSION Tai Chi augments resting levels of VZV-specific CMI and boosts VZV-CMI of the varicella vaccine OBJECTIVE To evaluate the effectiveness of Tai Chi in the treatment of knee osteoarthritis ( OA ) symptoms . METHODS We conducted a prospect i ve , single-blind , r and omized controlled trial of 40 individuals with symptomatic tibiofemoral OA . Patients were r and omly assigned to 60 minutes of Tai Chi ( 10 modified forms from classic Yang style ) or attention control ( wellness education and stretching ) twice weekly for 12 weeks . The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) pain score at 12 weeks . Secondary outcomes included WOMAC function , patient and physician global assessment s , timed chair st and , depression index , self-efficacy scale , and quality of life . We repeated these assessment s at 24 and 48 weeks . Analyses were compared by intent-to-treat principles . RESULTS The 40 patients had a mean age of 65 years and a mean body mass index of 30.0 kg/m(2 ) . Compared with the controls , patients assigned to Tai Chi exhibited significantly greater improvement in WOMAC pain ( mean difference at 12 weeks -118.80 mm [ 95 % confidence interval ( 95 % CI ) -183.66 , -53.94 ; P = 0.0005 ] ) , WOMAC physical function ( -324.60 mm [ 95 % CI -513.98 , -135.22 ; P = 0.001 ] ) , patient global visual analog scale ( VAS ; -2.15 cm [ 95 % CI -3.82 , -0.49 ; P = 0.01 ] ) , physician global VAS ( -1.71 cm [ 95 % CI -2.75 , -0.66 ; P = 0.002 ] ) , chair st and time ( -10.88 seconds [ 95 % CI -15.91 , -5.84 ; P = 0.00005 ] ) , Center for Epidemiologic Studies Depression Scale ( -6.70 [ 95 % CI -11.63 , -1.77 ; P = 0.009 ] ) , self-efficacy score ( 0.71 [ 95 % CI 0.03 , 1.39 ; P = 0.04 ] ) , and Short Form 36 physical component summary ( 7.43 [ 95 % CI 2.50 , 12.36 ; P = 0.004 ] ) . No severe adverse events were observed . CONCLUSION Tai Chi reduces pain and improves physical function , self-efficacy , depression , and health-related quality of life for knee OA Research in psychoneuroimmunology suggests that immunosuppression associated with perceived stress may contribute to disease progression in persons with HIV infection . While stress management interventions may enhance immune function , few alternative approaches have yet been tested . This r and omized clinical trial was conducted to test effects of three 10-week stress management approaches -- cognitive-behavioral relaxation training ( RLXN ) , focused tai chi training ( TCHI ) , and spiritual growth groups (SPRT)--in comparison to a wait-listed control group ( CTRL ) among 252 individuals with HIV infection . Using repeated measures mixed modeling , the authors found that in comparison to the CTRL group , ( a ) both the RLXN and TCHI groups used less emotion-focused coping , and ( b ) all treatment groups had augmented lymphocyte proliferative function . Despite modest effects of the interventions on psychosocial functioning , robust findings of improved immune function have important clinical implication s , particularly for persons with immune-mediated illnesses OBJECTIVE To determine whether Tai Chi or hydrotherapy classes for individuals with chronic symptomatic hip or knee osteoarthritis ( OA ) result in measurable clinical benefits . METHODS A r and omized controlled trial was conducted among 152 older persons with chronic symptomatic hip or knee OA . Participants were r and omly allocated for 12 weeks to hydrotherapy classes ( n = 55 ) , Tai Chi classes ( n = 56 ) , or a waiting list control group ( n = 41 ) . Outcomes were assessed 12 and 24 weeks after r and omization and included pain and physical function ( Western Ontario and McMaster Universities Osteoarthritis Index ) , general health status ( Medical Outcomes Study Short Form 12 Health Survey [ SF-12 ] , version 2 ) , psychological well-being , and physical performance ( Up and Go test , 50-foot walk time , timed stair climb ) . RESULTS At 12 weeks , compared with controls , participants allocated to hydrotherapy classes demonstrated mean improvements ( 95 % confidence interval ) of 6.5 ( 0.4 , 12.7 ) and 10.5 ( 3.6 , 14.5 ) for pain and physical function scores ( range 0 - 100 ) , respectively , whereas participants allocated to Tai Chi classes demonstrated improvements of 5.2 ( -0.8 , 11.1 ) and 9.7 ( 2.8 , 16.7 ) , respectively . Both class allocations achieved significant improvements in the SF-12 physical component summary score , but only allocation to hydrotherapy achieved significant improvements in the physical performance measures . All significant improvements were sustained at 24 weeks . In this almost exclusively white sample , class attendance was higher for hydrotherapy , with 81 % attending at least half of the available 24 classes , compared with 61 % for Tai Chi . CONCLUSION Access to either hydrotherapy or Tai Chi classes can provide large and sustained improvements in physical function for many older , sedentary individuals with chronic hip or knee OA OBJECTIVES To determine whether an intense tai chi ( TC ) exercise program could reduce the risk of falls more than a wellness education ( WE ) program in older adults meeting criteria for transitioning to frailty . DESIGN R and omized , controlled trial of 48 weeks duration . SETTING Twenty congregate living facilities in the greater Atlanta area . PARTICIPANTS Sample of 291 women and 20 men aged 70 to 97 . MEASUREMENTS Demographics , time to first fall and all subsequent falls , functional measures , Sickness Impact Profile , Centers for Epidemiologic Studies -Depression Scale , Activities-specific Balance Confidence Scale , Falls Efficacy Scales , and adherence to interventions . RESULTS The risk ratio ( RR ) of falling was not statistically different in the TC group and the WE group ( RR=0.75 , 95 % confidence interval (CI)=0.52 - 1.08 ) , P=.13 ) . Over the 48 weeks of intervention , 46 % ( n=132 ) of the participants did not fall ; the percentage of participants that fell at least once was 47.6 % for the TC group and 60.3 % for the WE group . CONCLUSION TC did not reduce the RR of falling in transitionally frail , older adults , but the direction of effect observed in this study , together with positive findings seen previously in more-robust older adults , suggests that TC may be clinical ly important and should be evaluated further in this high-risk population OBJECTIVE Depressive symptoms are common among patients with fibromyalgia , and behavioral intervention has been recommended as a major treatment component for this illness . The objective of this study was to test the effects of the Mindfulness-Based Stress Reduction ( MBSR ) intervention on depressive symptoms in patients with fibromyalgia . METHODS This r and omized controlled trial examined effects of the 8-week MBSR intervention on depressive symptoms in 91 women with fibromyalgia who were r and omly assigned to treatment ( n = 51 ) or a waiting-list control group ( n = 40 ) . Eligible patients were at least 18 years old , willing to participate in a weekly group , and able to provide physician verification of a fibromyalgia diagnosis . Of 166 eligible participants who responded to local television news publicizing , 49 did not appear for a scheduled intake , 24 enrolled but did not provide baseline data , and 2 were excluded due to severe mental illness , leaving 91 participants . The sample averaged 48 years of age and had 14.7 years of education . The typical participant was white , married , and employed . Patients r and omly assigned to treatment received MBSR . Eight weekly 2.5-hour sessions were led by a licensed clinical psychologist with mindfulness training . Somatic and cognitive symptoms of depression were assessed using the Beck Depression Inventory administered at baseline , immediately postprogram , and at followup 2 months after the conclusion of the intervention . RESULTS Change in depressive symptoms was assessed using slopes analyses of intervention effects over time . Depressive symptoms improved significantly in treatment versus control participants over the 3 assessment s. CONCLUSION This meditation-based intervention alleviated depressive symptoms among patients with fibromyalgia OBJECTIVE This study aim ed to assess the usefulness of two interventions in a group rehabilitation medicine setting to determine strategies and exercise guidelines for long-term care of the HIV/AIDS population with human immunodeficiency virus ( HIV ) and /or acquired immunodeficiency syndrome ( AIDS ) . DESIGN This was a r and omized clinical trial investigating the effects of tai chi ( TC ) and aerobic exercise ( EX ) on functional outcomes and quality of life ( QOL ) in patients with AIDS . SETTING Two outpatient infectious disease clinics in a mid-atlantic state were the setting . SUBJECTS AND INTERVENTION Thirty-eight ( 38 ) subjects with advanced HIV ( AIDS ) were r and omized to one of three groups : TC , EX , or control . Experimental groups exercised twice weekly for 8 weeks . OUTCOME MEASURES The primary outcomes included QOL as measured by the Medical Outcomes Short Form ( MOS-HIV ) and Spirituality Well-Being Scale ( SWB ) . Functional measures included the functional reach ( FR ) for balance , sit and reach ( SR ) for flexibility , and sit-up ( SU ) test for endurance . The physical performance test ( PPT ) was used to determine overall function , and the Profile of Mood States ( POMS ) was used to evaluate psychologic changes . To consider the patients ' explanations for these measurements , qualitative data were collected from subjects ' journals , focus groups , and nonparticipant observation . RESULTS Thirty-eight ( 38 ) subjects were included in data analysis : 13 in the TC group , 13 in the EX group , and 12 in the control group . Results of analysis of covariance showed significant changes in the exercise groups in overall functional measures ( p < 0.001 ) . The MOS-HIV showed a significant difference on the subscale of overall health ( p = 0.04 ) . The POMS showed significant main effect for time in confusion-bewilderment ( p = 0.000 ) and tension-anxiety ( p = 0.005 ) . Three dominant themes emerged from the qualitative data , including : positive physical changes , enhanced psychologic coping , and improved social interactions . CONCLUSIONS This study shows that TC and EX improve physiologic parameters , functional outcomes , and QOL . Group intervention provides a socialization context for management of chronic HIV disease . This study supports the need for more research investigating the effect of other types of group exercise for this population . This study sets the stage for a larger r and omized controlled trial to examine the potential short- and long-term effects of group exercise that may prove beneficial in the management of advanced HIV disease . Further research is warranted to evaluate additional exercise interventions that are accessible , safe , and cost-effective for the HIV population Changes in psychological and physiological functioning following participation in Tai Chi were assessed for 33 beginners and 33 practitioners . The variables in the three-way factorial design were experience ( beginners vs practitioners ) , time ( morning vs afternoon vs evening ) , and phase ( before Tai Chi vs during Tai Chi vs after Tai Chi ) . Phase was a repeated measures variable . Relative to measures taken beforeh and , practice of Tai Chi raised heart rate , increased noradrenaline excretion in urine , and decreased salivary cortisol concentration . Relative to baseline levels , subjects reported less tension , depression , anger , fatigue , confusion and state-anxiety , they felt more vigorous , and in general they had less total mood disturbance . The data suggest that Tai Chi results in gains that are comparable to those found with moderate exercise . There is need for research concerned with whether participation in Tai Chi has effects over and above those associated with physical exercise This study evaluated health benefits of a supported physical activity program for 116 older carers ( mean age 64.4 [ SD = 7.9 ] , 85 % women ) . Participants undertook a 6-month center-based physical activity program ( strength training , yoga , or Tai Chi ) . Eighty-eight participants ( 76 % ) completed the program . Multivariate repeated- measures ANOVA identified overall significant improvement postintervention ( p = .004 ) . Univariate analyses revealed significant improvements for balance , strength , gait endurance , depression , and SF-36 ( physical component ; p < .05 ) . There was no change in the Zarit Carer Burden Scale ( p > .05 ) . Change in performance scores did not differ significantly between those with higher and lower attendance at classes , although there was significantly greater improvement in gait endurance and balance ( p < .05 ) in those attending classes run twice weekly than in those attending once-weekly classes . In conclusion , a carer physical activity program , providing additional carer support to facilitate participation , can achieve high levels of involvement by carers and significant health benefits Psychological changes associated with 16-wk moderate and low intensity exercise training programs , two of which possessed a cognitive component , were evaluated . Subjects were healthy , sedentary adults , 69 women ( mean age = 54.8 + /- 8.3 yr ) and 66 men ( mean age = 50.6 + /- 8.0 yr ) . Participants were r and omly assigned to a control group ( C ) , moderate intensity walking group ( MW ) , low intensity walking group ( LW ) , low intensity walking plus relaxation response group ( LWR ) , or mindful exercise ( ME ) group-a Tai Chi type program . Women in the ME group experienced reductions in mood disturbance ( tension , P < 0.01 ; depression , P < 0.05 ; anger , P < 0.008 ; confusion , P < 0.02 ; and total mood disturbance , P < 0.006 ) and an improvement in general mood ( P < 0.04 ) . Women in the MW group noted greater satisfaction with physical attributes ( body cathexis , P < 0.03 ) , and men in MW reported increased positive affect ( P < 0.006 ) . No other differences were observed between groups on measures of mood , self-esteem , personality , or life satisfaction . Equivocal support is provided for the hypothesis that exercise plus cognitive strategy training programs are more effective than exercise programs lacking a structured cognitive component in promoting psychological benefits BACKGROUND / AIMS Rheumatoid arthritis ( RA ) is a serious health problem result ing in significant morbidity and disability . Tai Chi may be beneficial to patients with RA as a result of effects on muscle strength and ' mind-body ' interactions . To obtain preliminary data on the effects of Tai Chi on RA , we conducted a pilot r and omized controlled trial . Twenty patients with functional class I or II RA were r and omly assigned to Tai Chi or attention control in twice-weekly sessions for 12 weeks . The American College of Rheumatology ( ACR ) 20 response criterion , functional capacity , health-related quality of life and the depression index were assessed . RESULTS At 12 weeks , 5/10 patients ( 50 % ) r and omized to Tai Chi achieved an ACR 20 % response compared with 0/10 ( 0 % ) in the control ( p = 0.03 ) . Tai Chi had greater improvement in the disability index ( p = 0.01 ) , vitality subscale of the Medical Outcome Study Short Form 36 ( p = 0.01 ) and the depression index ( p = 0.003 ) . Similar trends to improvement were also observed for disease activity , functional capacity and health-related quality of life . No adverse events were observed and no patients withdrew from the study . CONCLUSION Tai Chi appears safe and may be beneficial for functional class I or II RA . These promising results warrant further investigation into the potential complementary role of Tai Chi for treatment of RA |
1,238 | 25,375,112 | In spite of the method ological shortcomings of the primary studies included in the systematic review , we reasonably conclude that implementation of high intensity aerobic interval training in subjects with metabolic syndrome , leads to increases in peak oxygen consumption | INTRODUCTION A number of cardiovascular risk factors characterizes the metabolic syndrome : insulin resistance ( IR ) , low HDL cholesterol and high triglycerides .
The aforementioned risk factors lead to elevated levels of abdominal adipose tissue , result ing in oxygen consumption deficiency .
PURPOSE To verify the validity and applicability of using high intensity interval training ( HIIT ) in subjects with metabolic syndrome and to answer the following question : Can HIIT improve peak oxygen consumption ? | We examined the effects of an 8-week exercise intervention on aerobic fitness , and roid and gynoid fat mass , and blood lipids in overweight and obese participants . Twenty-four sedentary participants ( average BMI = 30 ± 2 kg/m2 ; 18 females , 6 males ) were r and omized into either interval training and diet education ( INT group ) , continuous aerobic exercise and diet education ( CON group ) , or diet education only ( DIET group ) . Duration s of exercise sessions were similar ( ∼30 minutes ) , with both exercise groups completing the same amount of work . The INT and CON groups demonstrated significant improvements over time for ( p < 0.01 and p < 0.05 , ES = 1.1 and 1.2 , respectively ) and time to exhaustion on a grade d exercise test ( p < 0.01 and ES = 0.8 for both groups ) . Further , a large effect size ( 0.7 ) was recorded for the loss in and roid fat mass over time in the INT group only Regular exercise training is recognized as a powerful tool to improve work capacity , endothelial function and the cardiovascular risk profile in obesity , but it is unknown which of high-intensity aerobic exercise , moderate-intensity aerobic exercise or strength training is the optimal mode of exercise . In the present study , a total of 40 subjects were r and omized to high-intensity interval aerobic training , continuous moderate-intensity aerobic training or maximal strength training programmes for 12 weeks , three times/week . The high-intensity group performed aerobic interval walking/running at 85 - 95 % of maximal heart rate , whereas the moderate-intensity group exercised continuously at 60 - 70 % of maximal heart rate ; protocol s were isocaloric . The strength training group performed ' high-intensity ' leg press , abdominal and back strength training . Maximal oxygen uptake and endothelial function improved in all groups ; the greatest improvement was observed after high-intensity training , and an equal improvement was observed after moderate-intensity aerobic training and strength training . High-intensity aerobic training and strength training were associated with increased PGC-1alpha ( peroxisome-proliferator-activated receptor gamma co-activator 1alpha ) levels and improved Ca(2 + ) transport in the skeletal muscle , whereas only strength training improved antioxidant status . Both strength training and moderate-intensity aerobic training decreased oxidized LDL ( low-density lipoprotein ) levels . Only aerobic training decreased body weight and diastolic blood pressure . In conclusion , high-intensity aerobic interval training was better than moderate-intensity aerobic training in improving aerobic work capacity and endothelial function . An important contribution towards improved aerobic work capacity , endothelial function and cardiovascular health originates from strength training , which may serve as a substitute when whole-body aerobic exercise is contra-indicated or difficult to perform Background — Exercise training reduces the symptoms of chronic heart failure . Which exercise intensity yields maximal beneficial adaptations is controversial . Furthermore , the incidence of chronic heart failure increases with advanced age ; it has been reported that 88 % and 49 % of patients with a first diagnosis of chronic heart failure are > 65 and > 80 years old , respectively . Despite this , most previous studies have excluded patients with an age > 70 years . Our objective was to compare training programs with moderate versus high exercise intensity with regard to variables associated with cardiovascular function and prognosis in patients with postinfa rct ion heart failure . Methods and Results — Twenty-seven patients with stable postinfa rct ion heart failure who were undergoing optimal medical treatment , including & bgr;-blockers and angiotensin-converting enzyme inhibitors ( aged 75.5±11.1 years ; left ventricular [ LV ] ejection fraction 29 % ; & OV0312;o2peak 13 mL · kg−1 · min−1 ) were r and omized to either moderate continuous training ( 70 % of highest measured heart rate , ie , peak heart rate ) or aerobic interval training ( 95 % of peak heart rate ) 3 times per week for 12 weeks or to a control group that received st and ard advice regarding physical activity . & OV0312;o2peak increased more with aerobic interval training than moderate continuous training ( 46 % versus 14 % , P<0.001 ) and was associated with reverse LV remodeling . LV end-diastolic and end-systolic volumes declined with aerobic interval training only , by 18 % and 25 % , respectively ; LV ejection fraction increased 35 % , and pro-brain natriuretic peptide decreased 40 % . Improvement in brachial artery flow-mediated dilation ( endothelial function ) was greater with aerobic interval training , and mitochondrial function in lateral vastus muscle increased with aerobic interval training only . The MacNew global score for quality of life in cardiovascular disease increased in both exercise groups . No changes occurred in the control group . Conclusions — Exercise intensity was an important factor for reversing LV remodeling and improving aerobic capacity , endothelial function , and quality of life in patients with postinfa rct ion heart failure . These findings may have important implication s for exercise training in rehabilitation programs and future studies BACKGROUND Peak oxygen uptake ( Vo(2peak ) ) strongly predicts mortality in cardiac patients . We compared the effects of aerobic interval training ( AIT ) versus moderate continuous training ( MCT ) on Vo(2peak ) and quality of life after coronary artery bypass grafting ( CABG ) . METHODS Fifty-nine CABG patients were r and omized to either AIT at 90 % of maximum heart rate or MCT at 70 % of maximum heart rate , 5 d/wk , for 4 weeks at a rehabilitation center . Primary outcome was Vo(2peak ) , at baseline , after rehabilitation ( 4 weeks ) , and after 6 months of home-based exercise ( 6 months ) . RESULTS Vo(2peak ) increased between baseline and 4 weeks in AIT ( 27.1 + /- 4.5 vs 30.4 + /- 5.5 mL.kg(-1).min(-1 ) , P < .001 ) and MCT ( 26.2 + /- 5.2 vs 28.5 + /- 5.6 mL.kg(-1).min(-1 ) , P < .001 ; group difference , not significant ) . Aerobic interval training increased Vo(2peak ) between 4 weeks and 6 months ( 30.4 + /- 5.5 vs 32.2 + /- 7.0 mL.kg(-1).min(-1 ) , P < .001 ) , with no significant change in MCT ( 28.5 + /- 5.6 vs 29.5 + /- 5.7 mL.kg(-1).min(-1 ) ) . Quality of life improved in both groups from baseline to 4 weeks , remaining improved at 6 months . There were no changes in echocardiographic systolic and diastolic left ventricular function . Adiponectin increased between 4 weeks and 6 months in both groups ( group differences , not significant ) . CONCLUSIONS Four weeks of intense training increased Vo(2peak ) significantly after both AIT and MCT . Six months later , the AIT group had a significantly higher Vo(2peak ) than MCT . The results indicate that AIT and MCT increase Vo(2peak ) similarly in the short term , but with better long-term effect of AIT after CABG PURPOSE Autonomic dysfunction including sympathetic activation and vagal withdrawal has been reported in patients with chronic heart failure ( CHF ) . We tested the hypotheses that high-intensity interval exercise ( HIIE ) in CHF patients would enhance vagal modulation and thus decrease arrhythmic events . METHODS Eighteen CHF patients underwent a baseline assessment ( CON ) and were then r and omized to a single session of HIIE and to an isocaloric moderate-intensity continuous exercise ( MICE ) . We evaluated the HR , HR variability parameters , and arrhythmic events by 24-h Holter ECG recordings after HIIE , MICE , and CON sessions . RESULTS We found that HR was significantly decreased after HIIE ( 68 ± 3 bpm , P < 0.01 ) when compared with CON and MICE values ( 71.1 ± 2 and 69 ± 3 bpm , respectively ) . HIIE led to a significant increase in normalized high-frequency power ( 35.95 % ± 2.83 % vs 31.56 % ± 1.93 % and 24.61 % ± 2.62 % for CON and MICE , respectively , P < 0.01 ) . Both exercise conditions were associated with an increase in very low frequency power comparative to CON . After HIIE , premature ventricular contractions were significantly decreased ( 531 ± 338 vs 1007 ± 693 and 1671 ± 1604 for CON and MICE , respectively , P < 0.01 ) . An association was found between the changes in premature ventricular contraction and the changes in low-frequency/high-frequency ratio ( r = 0.66 , P < 0.01 ) in patients exposed to HIIE . CONCLUSION We demonstrate that a single session of HIIE improves autonomic profile of CHF patients , leading to significant reductions of HR and arrhythmic events in a 24-h posttraining period . Cardioprotective effects of HIIE in CHF patients need to be confirmed in a larger study population and on a long-term basis This study determined the cellular energetic and structural adaptations of elderly muscle to exercise training . Forty male and female subjects ( 69.2 + /- 0.6 yr ) were assigned to a control group or 6 mo of endurance ( ET ) or resistance training ( RT ) . We used magnetic resonance spectroscopy and imaging to characterize energetic properties and size of the quadriceps femoris muscle . The phosphocreatine and pH changes during exercise yielded the muscle oxidative properties , glycolytic ATP synthesis , and contractile ATP dem and . Muscle biopsies taken from the same site as the magnetic resonance measurements were used to determine myosin heavy chain isoforms , metabolite concentrations , and mitochondrial volume densities . The ET group showed changes in all energetic pathways : oxidative capacity ( + 31 % ) , contractile ATP dem and ( -21 % ) , and glycolytic ATP supply ( -56 % ) . The RT group had a large increase in oxidative capacity ( 57 % ) . Only the RT group exhibited change in structural properties : a rise in mitochondrial volume density ( 31 % ) and muscle size ( 10 % ) . These results demonstrate large energetic , but smaller structural , adaptations by elderly muscle with exercise training . The rise in oxidative properties with both ET and RT suggests that the aerobic pathway is particularly sensitive to exercise training in elderly muscle . Thus elderly muscle remains adaptable to chronic exercise , with large energetic changes accompanying both ET and RT Objective : To determine the effects of a 15-week high-intensity intermittent exercise ( HIIE ) program on subcutaneous and trunk fat and insulin resistance of young women . Design and procedures : Subjects were r and omly assigned to one of the three groups : HIIE ( n=15 ) , steady-state exercise ( SSE ; n=15 ) or control ( CONT ; n=15 ) . HIIE and SSE groups underwent a 15-week exercise intervention . Subjects : Forty-five women with a mean BMI of 23.2±2.0 kg m−2 and age of 20.2±2.0 years . Results : Both exercise groups demonstrated a significant improvement ( P<0.05 ) in cardiovascular fitness . However , only the HIIE group had a significant reduction in total body mass ( TBM ) , fat mass ( FM ) , trunk fat and fasting plasma insulin levels . There was significant fat loss ( P<0.05 ) in legs compared to arms in the HIIE group only . Lean compared to overweight women lost less fat after HIIE . Decreases in leptin concentrations were negatively correlated with increases in VO2peak ( r=−0.57 , P<0.05 ) and positively correlated with decreases in TBM ( r=0.47 ; P<0.0001 ) . There was no significant change in adiponectin levels after training . Conclusions : HIIE three times per week for 15 weeks compared to the same frequency of SSE exercise was associated with significant reductions in total body fat , subcutaneous leg and trunk fat , and insulin resistance in young women Background Increased aerobic exercise capacity appears to reduce both all-cause mortality and cardiovascular disease mortality . Physical exercise to improve peak oxygen uptake ( VO2peak ) is thus strongly recommended , however evidence regarding the most efficient training intensity for patients with coronary artery disease ( CAD ) is still lacking . The purpose of this r and omized study was therefore to assess the effects of high intensity aerobic interval exercise compared to moderate intensity exercise , representing the same total training load , for increasing VO2peak in stable CAD- patients . Methods Twenty-one stable CAD- patients were r and omized to supervised treadmill walking at either high intensity ( 80–90 % of VO2peak ) or moderate intensity ( 50–60 % of VO2peak ) three times a week for 10 weeks . Results After training VO2peak increased by 17.9 % ( P = 0.012 ) in the high intensity group and 7.9 % ( P = 0.038 ) in the moderate intensity group . The training-induced adaptation was significantly higher in the high intensity group ( P = 0.011 ) . Conclusions High intensity aerobic interval exercise is superior to moderate exercise for increasing VO2peak in stable CAD- patients . As VO2peak seems to reflect a continuum between health and cardiovascular disease and death , the present data may be useful in design ing effective training programmes for improved health in the future |
1,239 | 24,589,069 | Based from the pooled sensitivity of abnormal ultrasound findings with homogenous results ( p > 0.05 ) , the hypoechogenicity of the common extensor origin has the best combination of diagnostic sensitivity and specificity .
There is insufficient evidence supporting the use of Power Doppler Ultrasonogrophy , Real-time Sonoelastography and sonographic probe-induced tenderness in diagnosing LE .
Conclusions The use of Gray-scale Ultrasonography is recommended in objective ly diagnosing lateral epicondylalgia .
The presence of hypoechogenicity and bone changes indicates presence of a stressed common extensor origin-lateral epicondyle complex in elbows with lateral epicondylalgia .
In addition to diagnosis , detection of these abnormal ultrasound findings allows localization of pathologies to tendon or bone that would assist in design ing an appropriate treatment suited to patient ’s condition | Background Ultrasound is considered a reliable , widely available , non-invasive and inexpensive imaging technique for assessing soft tissue involvement in Lateral epicondylalgia .
Despite the number of diagnostic studies for Lateral Epicondylalgia , there is no consensus in the current literature on the best abnormal ultrasound findings that confirm lateral epicondylalgia . | PURPOSE The aim of this prospect i ve study was to compare the sensitivity and specificity of sonography with those of MRI in evaluating epicondylitis . METHODS The affected elbows of 11 patients with suspected epicondylitis were examined sonographically , and the contralateral ( normal ) elbow was also examined for comparison . In 10 of these patients , the affected elbow was also examined with MRI . In addition , both elbows of 6 volunteers without epicondylitis were examined sonographically ; 1 elbow of each volunteer was design ated as the " test " elbow and was examined with MRI . The sonograms of the patients ' affected elbows and the volunteers ' test elbows were paired with the sonograms of the contralateral elbows for comparison and were r and omly shown twice to 2 readers . These readers , working independently and without knowledge of the findings of MRI , were instructed to state whether each elbow was normal or affected by epicondylitis . The MRI scans were then shown to the readers for similar review . RESULTS Sonographic features of epicondylitis included outward bowing of the common tendon , presence of hypoechoic fluid subadjacent to the common tendon , thickening , decreased echogenicity , and ill-defined margins of the common tendon . Sensitivity for detecting epicondylitis ranged from 64 % to 82 % for sonography and from 90 % to 100 % for MRI . Specificity ranged from 67 % to 100 % for sonography and from 83 % to 100 % for MRI . CONCLUSIONS Sonography is as specific but not as sensitive as MRI for evaluating epicondylitis . Used as an initial imaging tool , sonography might be adequate for diagnosing this condition in many patients , thus allowing MRI to be reserved for patients with symptoms whose sonographic findings are normal PURPOSE To determine the sensitivity and specificity of ultrasonography ( US ) in the detection of lateral epicondylitis and identify the US findings that are most strongly associated with symptoms . MATERIAL S AND METHODS Internal review board approval was obtained for retrospective review of the patient images , and the need for informed consent was waived . Internal review board approval was also obtained for scanning the 10 volunteers , all of whom gave informed consent . The study was compliant with the Health Insurance Portability and Accountability Act . US of the common extensor tendon was performed in 20 elbows in 10 asymptomatic volunteers ( six men , four women ; age range , 22 - 38 years ; mean age , 29.6 years ) and 37 elbows in 22 patients with symptoms of lateral epicondylitis ( 10 men , 12 women ; age range , 30 - 59 years ; mean age , 46 years ) . Fifty-seven representative images , one from each elbow , were r and omly assorted and interpreted by three independent readers who rated each common extensor tendon as normal or abnormal . Abnormal images were further classified as demonstrating one or more of eight US findings . Readers interpreted each image at two separate sessions to determine intrareader variability . The authors calculated the sensitivity and specificity of US in the diagnosis of lateral epicondylitis and the odds ratio for each US finding . Odds ratios were considered statistically significant at P < .05 when 95 % confidence intervals did not include one . RESULTS Sensitivities of US in the detection of symptomatic lateral epicondylitis ranged from 72 % to 88 % and specificities from 36 % to 48.5 % . Odds ratios for the following findings were statistically significant ( P < .05 ) for both reading sessions : calcification of common extensor tendon , tendon thickening , adjacent bone irregularity , focal hypoechoic regions , and diffuse heterogeneity . Odds ratios for lateral epicondyle enthesophytes were statistically significant ( P < .05 ) for the first reading session only . Odds ratios for linear intrasubstance tears and peritendinous fluid were not statistically significant . CONCLUSION US of the common extensor tendon had high sensitivity but low specificity in the detection of symptomatic lateral epicondylitis . The relationship between symptoms and intratendinous calcification , tendon thickening , adjacent bone irregularity , focal hypoechoic regions , and diffuse heterogeneity was statistically significant OBJECTIVES Following a consensus statement from a multidisciplinary UK workshop , a structured examination schedule was developed for the diagnosis and classification of musculoskeletal disorders of the upper limb . The aim of this study was to test the repeatability and the validity of the newly developed schedule in a hospital setting . METHOD 43 consecutive referrals to a soft tissue rheumatism clinic ( group 1 ) and 45 subjects with one of a list of specific upper limb disorders ( including shoulder capsulitis , rotator cuff tendinitis , lateral epicondylitis and tenosynovitis ) ( group 2 ) , were recruited from hospital rheumatology and orthopaedic outpatient clinics . All 88 subjects were examined by a research nurse ( blinded to diagnosis ) , and everyone from group 1 was independently examined by a rheumatologist . Between observer agreement was assessed among subjects from group 1 by calculating Cohen 's κ for dichotomous physical signs , and mean differences with limits of agreement for measured ranges of joint movement . To assess the validity of the examination , a pre-defined algorithm was applied to the nurse 's examination findings in patients from both groups , and the sensitivity and specificity of the derived diagnoses were determined in comparison with the clinic 's independent diagnosis as the reference st and ard . RESULTS The between observer repeatability of physical signs varied from good to excellent , with κ coefficients of 0.66 to 1.00 for most categorical observations , and mean absolute differences of 1.4 ° –11.9 ° for measurements of shoulder movement . The sensitivity of the schedule in comparison with the reference st and ard varied between diagnoses from 58%–100 % , while the specificities ranged from 84%–100 % . The nurse and the clinic physician generally agreed in their diagnoses , but in the presence of shoulder capsulitis the nurse usually also diagnosed shoulder tendinitis , whereas the clinic physician did not . CONCLUSION The new examination protocol is repeatable and gives acceptable diagnostic accuracy in a hospital setting . Examination can feasibly be delegated to a trained nurse , and the protocol has the benefit of face and construct validity as well as consensus backing . Its performance in the community , where disease is less clear cut , merits separate evaluation , and further refinement is needed to discriminate between discrete pathologies at the shoulder The histopathologic features from 11 patients who were treated surgically for lateral epicondylitis were grade d and compared to similar tissue from 12 cadaveric spec imens . All studies were done by a single pathologist who had no knowledge of the origin of the specimen . The surgical specimens were interpreted as abnormal in all 11 specimens , and all 12 of the control specimens were reported as being without histologic abnormality . Vascular proliferation was present in 10 of 11 and focal hyaline degeneration was recorded in all 11 of the surgical specimens . Neither feature was present in any of the control material ( P < 0.001 ) . These data suggest that chronic refractory lateral epicondylitis requiring sur gery is a degenerative rather than inflammatory proc ess . This may account for the lack of response to rest and antiinflammatory medication OBJECTIVE The purpose of this article is to evaluate prospect ively the utility of sonographic measurements of the common extensor tendon for diagnosing lateral epicondylitis . SUBJECTS AND METHODS Forty-eight patients with documented lateral epicondylitis and 63 healthy volunteers were enrolled and underwent ultrasound of the elbow joint . The common extensor tendon overlying the bony l and mark was scanned transversely , and the cross-section area and the maximum thickness were measured . Clinical examination was used as the reference st and ard in the diagnosis of lateral epicondylitis . Data from the patient and control groups were compared with established optimal diagnostic criteria for lateral epicondylitis using receiver operating characteristic curves . Qualitative evaluation with grayscale ultrasound was also performed on patients and healthy volunteers . RESULTS The common extensor tendon was significantly thicker in patients with lateral epicondylitis than in control subjects ( p < 0.01 ) . Tendon thickness greater than 4.2 mm ( sensitivity , 78.4 % ; specificity , 95.2 % ; accuracy , 87.7 % ) and area larger than or equal to 32 mm(2 ) ( sensitivity , 86.3 % ; specificity , 82.5 % ; accuracy , 84.2 % ) were highly predictive of lateral epicondylitis . For qualitative evaluation with gray-scale ultrasound , overall sensitivity , specificity , and accuracy values in the diagnosis of lateral epicondylitis were 76.5 % , 76.2 % , and 76.3 % , respectively . CONCLUSION The quantitative sonographic measurements had an excellent diagnostic performance for lateral epicondylitis , as well as good or excellent interreader agreement . A common extensor tendon cross-section area greater than or equal to 32 mm(2 ) and a thickness of 4.2 mm correlated well with the presence of lateral epicondylitis . However , further prospect i ve study is necessary to determine whether quantitative ultrasound with these cutoff values can improve the accuracy of the diagnosis of lateral epicondylitis OBJECTIVE Tennis elbow is a common complaint . Several treatment strategies have been described , but an optimal strategy has not been identified . Sonographic imaging as a predictive factor has never been studied . The aim of our study was to determine the value of sonographic findings in predicting response to conservative therapy for tennis elbow . This was done in a r and omized controlled trial in which the effectiveness of a brace only , physical therapy only , and a combination of both were compared . SUBJECTS AND METHODS Patients with tennis elbow complaints were r and omized . Sonography was performed before r and omization in 57 patients . Outcome measures at 6 weeks ' follow-up were success rate and decrease in pain ( scale , 0 - 100 ) . Data were analyzed using an intention-to-treat analysis . RESULTS In only 75 % of the imaged patients , sonographic abnormalities were identified and the clinical diagnosis could thus be confirmed . The following entities were identified : hypo- and hyperechogenicity , swelling , calcification , bursitis , enthesopathy , and tendinosis . The positive predictive value of sonography for the different entities varied between 0.78 and 0.82 , and the negative predictive value ranged between 0.23 and 0.71 . Predictive value was studied by subgroups of sonographic findings : hypoechoic , swelling present , enthesopathy , any entity present , and no entity present . We found no significant differences among the subgroups for either success rate ( range , 40 - 54 % ) or mean decrease in pain ( range , 16 - 28 percentage points ) . CONCLUSION No predictive value of sonography for the detection of abnormalities was identified in this study . Its diagnostic capability showed limited value . However , limitations in this study necessitate drawing definitive conclusions with care |
1,240 | 27,199,385 | Overall , nearly half the studies reported that baseline depression/anxiety was associated with some type of later smoking behavior , while over a third found evidence that a smoking exposure was associated with later depression/anxiety .
The results varied considerably , with evidence for smoking both associated with subsequent depression and anxiety , and vice versa .
Suggesting that despite advantages of longitudinal studies , they can not alone provide strong evidence of causality . | Background : Many studies report a positive association between smoking and mental illness .
However , the literature remains mixed regarding the direction of this association .
We therefore conducted a systematic review evaluating the association of smoking and depression and /or anxiety in longitudinal studies . | BACKGROUND Epidemiologic studies have reported an association between major depression and smoking . This prospect i ve study examines the role of depression in smoking progression and cessation , and the role of smoking in first-onset major depression . METHODS Data are from a 5-year longitudinal epidemiologic study of 1007 young adults . Incidence and odds ratios ( ORs ) are based on the prospect i ve data . Hazards ratios are based on the combined lifetime data and estimated in Cox proportional hazards models with time-dependent covariates . RESULTS Based on the prospect i ve data , history of major depression at baseline increased significantly the risk for progression to daily smoking ( OR , 3.0 ; 95 % confidence interval , 1.1 - 8.2 ) , but did not decrease significantly smokers ' rate of quitting ( OR , 0.8 ; 95 % confidence interval , 0.4 - 1.6 ) . History of daily smoking at baseline increased significantly the risk for major depression ( OR , 1.9 ; 95 % confidence interval , 1.1 - 3.4 ) . These estimates were reduced somewhat when history of early ( ie , before age 15 years ) conduct problems was controlled . Estimates based on lifetime data were consistent with these results . CONCLUSIONS The observed influences from major depression to subsequent daily smoking and smoking to major depression support the plausibility of shared etiologies . Separate causal mechanisms in each direction might also operate , including self-medication of depressed mood as a factor in smoking progression and neuropharmacologic effects of nicotine and other smoke substances on neurotransmitter systems linked to depression Objective : Previous research has indicated an association between smoking and depression in adolescents , although the nature of the relationship is controversial . We sought to underst and this relationship better in a prospect i ve study by investigating whether there are sub population s of adolescents with different relationships between smoking and depressive symptoms . Methods : Our sample was 925 adolescents attending one of five Northern Virginia high schools , grade s 9 to 12 . We used General Growth Mixture Modeling as our method because it allowed identification and characterization of depressive symptoms trajectories and assessment of the effects of trajectory on 12th grade smoking . We defined the binary variable 12th grade current smoking as smoking on 1 or more of the past 30 days and more than 100 cigarettes smoked in a lifetime , versus not having smoked in the past 30 days . Results : We identified three trajectories : high , medium , and low depressive symptoms . For adolescents with high symptoms , 9th grade ( baseline ) smoking was associated with an overall deceleration of depressive symptoms , whereas for adolescents with moderate symptoms , baseline smoking was associated with an overall acceleration in depressive symptoms . Baseline smoking was not associated with rate of change in depressive symptoms for adolescents with low symptoms , nor was it associated with baseline depressive symptoms in any trajectory . Conclusion : These findings demonstrate that there is a relationship between smoking and depressive symptoms in adolescents , and that the relationship can vary by developmental trajectory , suggesting etiological heterogeneity . GGMM = General Growth Mixture Modeling ; CES-D = Center for Epidemiological Studies Depression ; GMM = Growth Mixture Modeling ; BIC = Bayesian Information Criterion ; LMR LRT = Lo-Mendell-Rubin Likelihood Ratio ; OR = odds ratio ; CI = confidence interval Although it has been hypothesized that depressive persons have an excess risk of cancer , few prospect i ve data are available . The association between depressiveness and subsequent incidence of lung cancer was studied in the nationally representative Mini-Finl and Health Survey . The study population comprised 7,018 adult men and women , free from cancer at the baseline , carried out in 1978 - 1980 . During a 14-year follow-up , 605 cancer cases occurred , of which 70 were male lung cancer patients . Mental problems and disorders were assessed at the baseline examination using st and ard interview techniques ( General Health Question naire and Present State Examination ) . The relative risk of lung cancer between depressive persons and individuals with a normal depressiveness score was 3.32 ( 95 % confidence interval 1.53 - 7.20 ) . Neither adjustment for the potential confounding factors of age , education , geographic area , smoking , alcohol consumption , body mass index , serum cholesterol , leisure-time exercise , general health , and use of antidepressant medication nor exclusion of cancer cases occurring during the first 4 years of follow-up notably altered the results . There was a strong interaction between depressiveness and smoking . The relative risks of lung cancer between smokers and nonsmokers were 3.38 ( 95 % confidence interval 1.09 - 10.52 ) at normal depressiveness score levels and 19.67 ( 95 % confidence interval 2.57 - 150.7 ) at strongly elevated levels , respectively . It is possible that depressiveness modifies the effect of smoking on lung cancer risk either by biologic mechanisms or by affecting smoking behavior Smokers have a higher prevalence of major depressive episodes and depressive symptoms than the general population , but whether this association is causal , or is due to confounding or reverse causation is uncertain because of the problems inherent in some epidemiological studies . Mendelian r and omization , in which a genetic variant is used as a surrogate for measuring exposure , is an approach which may be used to better underst and this association . We investigated the rs1051730 single nucleotide polymorphism in the nicotine acetylcholine receptor gene cluster ( CHRNA5-CHRNA3-CHRNB4 ) , associated with smoking phenotypes , to determine whether women who continued to smoke were also more likely to report a low mood during pregnancy . We found among women who smoked pre-pregnancy , those with the 1051730 T allele smoked more and were less likely to quit smoking during pregnancy , but were also less likely to report high levels of depressed mood at 18 weeks of pregnancy ( per allele OR = 0.84 , 95%CI 0.72 to 0.99 , p = 0.034 ) . The association between genotype and depressed mood was limited to women who were smokers prior to pregnancy , with weak evidence of an interaction between smoking status and genotype ( p = 0.07 ) . Our results do not support a causal role of smoking on depressed mood , but are consistent with a self-medication hypothesis , whereby smoking is used to alleviate symptoms of depression . A replication study using multiple genetic variants which influence smoking via different pathways is required to confirm these findings and provide evidence that the genetic variant is reflecting the effect of quitting smoking on depressed mood , and is not directly affecting mood INTRODUCTION Smoking research and intervention efforts have neglected older women . Depressive symptoms , which are common in middle-aged and older women , are related to the maintenance of adult smoking . METHODS This study investigated the relation of a composite measure of current depressive symptoms , derived from a short form of the Center for Epidemiological Studies Depression Scale , and history of depressive symptoms , derived from two items from the Diagnostic Interview Schedule , to smoking outcomes in the Women 's Health Initiative Observational Study ( N = 90,627 ) . Participants were postmenopausal with an average age of 63.6 years at baseline . Participants were recruited from urban , suburban , and rural areas surrounding 40 clinical centers in the United States . Analyses controlled for age , educational level , and ethnicity . RESULTS In multinomial logistic regression analyses , depressive symptoms were related cross-sectionally to current light ( odds ratio [ OR ] = 1.19 , 95 % CI = 1.14 - 1.23 ) and heavier ( OR = 1.28 , 95 % CI = 1.23 - 1.32 ) smoking at baseline compared with nonsmokers . In prospect i ve multiple logistic regression analyses , baseline depressive symptoms were negatively predictive of smoking cessation at a 1-year follow-up ( OR = .85 , 95 % CI = 0.77 - 0.93 ) and at participants ' final assessment s in the study ( OR = .92 , 95 % CI = 0.85 - 0.98 ) . Light smokers had more than 2 times higher odds of smoking cessation than did heavier smokers . CONCLUSIONS The present findings demonstrate a consistent link between depressive symptoms and negative smoking-related behaviors among middle-aged and older women at both light and heavier smoking levels Using data from a 4-wave longitudinal study with a school-based sample of 1,218 middle adolescents , the authors investigated the directionality ( e.g. , unidirectionality and bidirectionality ) of the prospect i ve relationship between depressive symptoms and cigarette use within the context of potential confounding variables and common and unique intrapersonal and interpersonal predictors . Findings indicated that serious and persistent depressive symptoms were prospect i ve predictors of increased cigarette use across time , after controlling for baseline levels of smoking . Similarly , heavy and persistent smoking prospect ively predicted increases in depressive symptoms . Intrapersonal and interpersonal predictors of cross-temporal changes in depressive symptoms and cigarette use were more unique than common . Latent growth curve modeling indicated a quadratic trend in adolescent cigarette smoking across time with an initial acceleration followed by a deceleration , though there was substantial intraindividual variation in individual trajectories OBJECTIVE This study aim ed to develop a simple risk table of modifiable factors prospect ively associated with depression in later life that could be used to guide the assessment , management and introduction of preventive strategies in clinical practice . METHODS This retrospective cohort study included 4636 men aged 65 to 83 years living in the community who denied history of past diagnosis or treatment for depression . They self-reported information about their physical activity , weight and height , smoking history , alcohol consumption and dietary habits , as well as history of hypertension , diabetes , coronary heart disease and stroke . We calculated the body mass index ( BMI ) in kg/m(2 ) . Three to 8 years later they were assessed with the Geriatric Depression Scale 15 ( GDS-15 ) and those with a total score of 7 or greater were considered to display clinical ly significant symptoms of depression . We used binomial exponentiated log-linked general linear models to estimate the risk ratio ( RR ) and 95 % confidence interval ( 95 % CI ) of incident depression after adjusting for age , education , marital status and prevalent medical illnesses . We calculated the probability of depression for each individual combination of risk factors and displayed the results in a risk table . RESULTS Two hundred and twenty-nine men ( 4.5 % ) showed evidence of incident depression 5.7±0.9 ( mean±st and ard deviation ) years later . Measured dietary factors showed no association with incident depression . The probability of depression was the highest for older men who were underweight , overweight or obese , physically inactive , risk drinkers and smokers ( 12.0 % , 95 % CI=7.0 % , 17.1 % ) , and the lowest for those who had all 4 healthy lifestyle markers : physically active , normal body mass , non-risk drinking and non-smoking ( 1.6 % , 95 % CI=0.6 % , 2.5 % ) . The probability of incident depression fell between these two extremes for different combinations of lifestyle practice s. CONCLUSION Four modifiable lifestyle factors can be used in combination to produce a risk table that predicts the probability of incident depression over a period of 3 to 8 years . The risk table is simple , informative and can be easily incorporated into clinical practice to guide assessment and risk reduction interventions BACKGROUND The aim of the present study was to investigate the stability and longitudinal association between depression and smoking status within a community sample with type 2 diabetes ( T2D ) while controlling for sociodemographic and disease-related variables . METHODS Adults with T2D were recruited and agreed to be followed-up via r and om digit dialing for the Montreal Diabetes Health Study . At baseline , 1614 individuals were classified as never ( n = 592 ) , former ( n = 690 ) , light ( ≤10 cigarettes a day ; n = 128 ) and moderate-heavy ( 11 + cigarettes a day ; n = 204 ) smokers . Depression was assessed using the Patient Health Question naire-9 and individuals were classified as either " none " or having depression syndrome . Generalized estimating equations were used to test the association between depression syndrome and current smoking status while controlling for other demographic and health-related variables . RESULTS Prevalence rates of smoking and depression showed mild to substantial agreement over time . Depression syndrome was significantly associated with moderate-heavy smoking in the fully adjusted model using cross-sectional ( all four waves ; odds ratio [ OR ] 1.46 ; 95 % confidence interval [ CI ] 1.08 - 1.99 ; P < 0.05 ) and longitudinal ( controlling for depression at baseline ; OR 1.54 ; 95 % CI 1.02 - 2.31 ; P < 0.05 ) data . CONCLUSIONS Smoking and depression prevalence rates appear to be stable over time in our community sample with T2D . Moderate-heavy smoking is strongly associated with elevated depression , both in cross-sectional and longitudinal models . Persistent moderate-heavy smokers may be at increased risk of both physical and mental health complications . This burden is even greater for those with T2D Both depression and smoking are highly prevalent and related to poorer outcomes in cardiac patients . In this study , the authors examined the association between depressive symptoms and smoking status , described the frequency and type of antidepressant use , and prospect ively tested the effects of antidepressant use in smokers on smoking status and psychosocial outcomes . Participants comprised 1,498 coronary artery disease ( CAD ) out patients who completed a baseline survey which assessed depressive symptoms , current medications , and smoking status . A second survey was mailed 9 months later that assessed depressive symptoms , anxiety , insomnia and smoking status . Results showed that current and former-smokers had significantly greater depressive symptoms than non-smokers . Ten percent of patients were taking antidepressants , most frequently SSRIs , with significantly more smokers on antidepressants than former and non-smokers . At follow-up , smokers on antidepressants were less likely to have quit , had greater anxiety , depressive symptoms and insomnia than smokers not using antidepressants . This study demonstrated that smokers and quitters with CAD had greater depressive symptoms and use of antidepressants than non-smokers , but that the antidepressants utilized may not be optimizing outcomes AIMS To examine the prospect i ve relationships between childhood externalizing and internalizing disorders and substance use in early adolescence . DESIGN Longitudinal , community-based study of twins ( aged 11 at intake ; aged 14 at follow-up ) . SETTING AND PARTICIPANTS The sample was composed of twins participating in the Minnesota Twin Family Study , an epidemiological sample of twins and their families representative of the state population of Minnesota . A total of 699 twin girls and 665 twin boys participated at both time-points . MEASUREMENTS Twins participated in in-person , life-time diagnostic assessment s of the following childhood DSM III-R externalizing and internalizing disorders at age 11 : conduct disorder , oppositional defiant disorder , attention deficit hyperactivity disorder , major depressive disorder and in addition , for girls only , overanxious disorder and separation anxiety disorder . At ages 11 and 14 , substance use and abuse were assessed . FINDINGS Externalizing psychopathology predicted having tried alcohol , nicotine and cannabis by age 14 as well as regular and advanced experience with these substances . Internalizing disorders showed weak effects , with only major depression at age 11 showing a significant relationship with substance use at age 14 . CONCLUSION The results suggest that externalizing psychopathology is a robust prospect i ve predictor of a variety of early onset substance use behaviors and is systematic ally related to degree of substance use involvement . The results also suggest that depression may predict initiation of licit substance use in early adolescence OBJECTIVES . The purpose of this work was to identify characteristics that predict progression from the first inhalation of a cigarette to dependence . We studied a cohort of 1246 public school 6th- grade rs in 6 Massachusetts communities ( mean age at baseline : 12.2 years ) . METHODS . We conducted a 4-year prospect i ve study using 11 interviews . We assessed 45 risk factors and measured diminished autonomy over tobacco with the Hooked on Nicotine Checklist and evaluated tobacco dependence according to the International Classification of Diseases , 10th Revision . Cox proportional-hazards models were used . RESULTS . Among 217 youths who had inhaled from a cigarette , the loss of autonomy over tobacco was predicted by feeling relaxed the first time inhaling from a cigarette and depressed mood . Tobacco dependence was predicted by feeling relaxed , familiarity with Joe Camel , novelty seeking , and depressed mood . CONCLUSIONS . Once exposure to nicotine had occurred , remarkably few risk factors for smoking consistently contributed to individual differences in susceptibility to the development of dependence or loss of autonomy . An experience of relaxation in response to the first dose of nicotine was the strongest predictor of both dependence and lost autonomy . This association was not explained by trait anxiety or any of the other measured psychosocial factors . These results are discussed in relation to the theory that the process of dependence is initiated by the first dose of nicotine AIMS To investigate prospect i ve associations between psychopathology in adolescence and tobacco , alcohol and drug use in young adulthood . DESIGN A sample of 787 10 - 14-year-olds from the Dutch general population was prospect ively followed-up across an 8-year interval . The Child Behavior Checklist ( CBCL ) was administered at initial assessment , and at 2- and 4-year follow-ups . Substance abuse was assessed with the Young Adult Self-Report ( YASR ) at 8-year follow-up . FINDINGS The Thought Problems scale of the CBCL was the strongest predictor of alcohol use , while smoking was predicted by the Thought Problems and Delinquent Behavior scales . The strongest association with drug use in young adulthood was for the CBCL Delinquent Behavior scale . Predictive value of predictors in early adolescence was as important as in late adolescence . CONCLUSION To investigate pathways towards substance use in young adulthood , studies assessing a broad range of possible predictors , including Thought Problems , at different developmental stages of adolescence , are needed BACKGROUND Epidemiological research is believed to underestimate the lifetime prevalence of mental illness due to recall failure and a lack of rapport between research ers and participants . METHOD In this prospect i ve study , we examined lifetime prevalence and co-morbidity rates of substance use disorders , antisocial personality disorder ( ASPD ) and major depressive disorder ( MDD ) in a representative , statewide Minnesota sample ( n = 1252 ) assessed four times between the ages of 17 and 29 years with very low attrition . RESULTS Lifetime prevalence rates of all disorders more than doubled between the ages of 17 and 29 years in both men and women , and our prospect i ve rates at the age of 29 years were consistently higher than rates from leading epidemiological surveys . Although there was some variation , the general trend was for lifetime co-morbidity to increase between the ages of 17 and 29 years , and this trend was significant for MDD-alcohol dependence , MDD-nicotine dependence , and ASPD-nicotine dependence . CONCLUSIONS Overall , our results show that emerging adulthood is a high-risk period for the development of mental illness , with increases in the lifetime prevalence and co-morbidity of mental disorders during this time . More than a quarter of individuals had met criteria for MDD and over a fifth had experienced alcohol dependence by the age of 29 years , indicating that mental illness is more common than is estimated in cross-sectional mental health surveys . These findings have important implication s for the measurement of economic burden , re source allocation toward mental health services and research , advocacy organizations for the mentally ill , and etiological theories of mental disorders BACKGROUND A key question regarding the documented association between smoking and depression is whether it reflects a causal influence of smoking on depression ; however , only a limited number of longitudinal studies exist in the literature , all of which have relatively short time frames . The purpose was to prospect ively assess the risk of depression according to daily tobacco consumption in a Danish longitudinal study . METHODS A prospect i ve cohort study , the Copenhagen City Heart Study ( n = 18,146 ) , was analyzed with up to 26 years of follow-up . It contains three up date d data sets on tobacco consumption and potential confounding factors . The study population was linked to Danish hospital registers to detect registration s with depression . Individuals with depression before baseline were excluded . RESULTS Women smoking more than 10 g of tobacco per day were at significantly increased risk of depression compared to women who did not smoke . The adjusted risk of depression among women smoking 11 - 20 g per day was 1.74 ( CI:1.33 - 2.27 ) and 2.17 ( CI:1.45 - 3.26 ) among women smoking more than 20 g per day . For men , there was an increased risk of depression for those smoking more than 20 g per day ( HR = 1.90 ; CI:1.05 - 3.44 ) . All tests for linear trend were significant ( all p < 0.01 ) . The estimates remained significant in sensitivity analyses aim ing to eliminate reverse causation , and in analyses based on a reduced sample without individuals with chronic diseases or psychiatric disorders other than depression . CONCLUSION The study suggests that smoking is associated with increased risk of developing depression . This underlines the potentially harmful consequences of smoking for mental health and supports efforts to prevent and stop smoking AIMS The comorbidity of mental disorders and substance dependence is well documented , but prospect i ve investigations in community sample s are rare . This investigation examines the role of primary mental disorders as risk factors for the later onset of nicotine , alcohol and illicit drug use , abuse and dependence with abuse . DESIGN The National Comorbidity Survey ( NCS ) was a nationally representative survey of mental and substance disorders in the United States carried out in 1990 - 92 . The NCS-2 re-interviewed a probability sub sample of NCS respondents in 2001 - 03 , a decade after the baseline survey . PARTICIPANTS A total of 5001 NCS respondents were re-interviewed in the NCS-2 ( 87.6 % of baseline sample ) . RESULTS Aggregate analyses demonstrated significant prospect i ve risks posed by baseline mental disorders for the onset of nicotine , alcohol and illicit drug dependence with abuse over the follow-up period . Particularly strong and consistent associations were observed for behavioral disorders and previous substance use conditions , as well as for certain mood and anxiety disorders . Conditional analyses demonstrated that many observed associations were limited to specific categories of use , abuse or dependence , including several mental disorders that were non-significant predictors in the aggregate analyses . CONCLUSIONS Many mental disorders are associated with an increased risk of later substance use conditions , but important differences in these associations are observed across the categories of use , abuse and dependence with abuse . These prospect i ve findings have implication s for the precision of prevention and treatment strategies targeting substance use disorders This study examined the psychosocial predictors of nicotine dependence in Blacks and Puerto Ricans . A longitudinal , prospect i ve study design was employed . Data on five psychosocial domains were obtained from a four-wave study of tobacco use and smoking behavior ; data were analyzed using logistic regression . Participants ( N = 475 ) included adult Blacks and Puerto Ricans initially recruited from urban public schools in New York City and interviewed when they were mean age 14 years , and then again when they were mean ages 19 , 24 , and 26 years . Structured interviews were administered at four points in time over a period of 12 years . Nicotine dependence was measured using a DSM-IV adapted version of the Composite International Diagnostic Interview nicotine dependence measure . Logistic regression analyses showed that factors in each of five psychosocial domains ( personality , drug use behavior , family , peer , and environment ) significantly predicted nicotine dependence . The pattern of results was similar for both Black and Puerto Rican sample s. Factors that protected against nicotine dependence included achievement , ego-integration , and a positive school climate . The findings indicate that a variety of risk factors contribute to the occurrence of nicotine dependence . When examining the causes of nicotine dependence , it is important to investigate an array of biopsychosocial and environmental factors AIMS It is well established that tobacco use is associated with mental disorders . However , the association between tobacco use and mental disorders has not yet been examined sufficiently in prospect i ve , population -based studies . The current study is aim ed at examining whether smoking is associated with first-ever incidence of mental disorders . DESIGN , SETTING AND PARTICIPANTS We conducted a prospect i ve , population -based epidemiological study ( the Netherl and s Mental Health Survey and Incidence Study : NEMESIS ) in which a representative sample of adults aged 18 - 64 years ( n = 7076 ) were interviewed to establish the presence of a broad range of mental disorders . We re-interviewed them at 1 year ( n = 5618 ; response 79.4 % ) and 3 years ( n = 4796 ; 67.8 % ) after baseline . MEASUREMENTS The presence of mental disorders was assessed according to DSM-III-R criteria with the Composite International Diagnostic Interview ( CIDI ) , which was administered by trained lay interviewers . Tobacco use was assessed by asking respondents whether they had smoked in the past year , and how many cigarettes they smoked . FINDINGS Subjects who smoked but never had a mental disorder in their life , had an increased risk of developing a mental disorder ( P < 0.01 ) , and this remained significant after correcting for major risk indicators of mental disorders . CONCLUSIONS Smoking is associated not only with the prevalence , but also with first-ever incidence of mental disorders . More research is needed to study the causal pathways OBJECTIVE To examine cross-sectionally and prospect ively relationships of cigarette smoking with major depressive disorder ( MDD ) , controlling for comorbidity in a community sample of adolescents . METHOD A representative sample of 1,709 adolescents ( aged 14 through 18 years ) was assessed by using semistructured diagnostic interviews on two occasions , approximately 1 year apart . Logistic regression analyses were used to examine cross-sectionally and prospect ively the relationships between smoking and each psychiatric disorder , while statistically controlling for the other disorders . RESULTS Cross-sectional analyses revealed significant relationships of drug abuse/dependence and disruptive behavior disorders with adolescent smoking , even after the co-occurrence of all other disorders was controlled . Prospect ively , smoking was found to increase the risk of developing an episode of MDD and drug abuse/dependence , after adjusting for other disorders . Finally , only lifetime prevalence of MDD remained a significant predictor of smoking onset , after controlling for other disorders . Gender did not moderate any of the relationships between psychopathology and smoking . CONCLUSIONS The results suggest important relationships between cigarette smoking and psychiatric disorders among adolescents , particularly with regard to MDD , drug abuse/dependence , and disruptive behavior disorders . These findings have important clinical implication s , both for psychiatric care and for smoking prevention and cessation efforts with adolescents AIMS To examine whether child and adolescent psychopathology predicts subsequent tobacco use at 14 and 21 years of age . DESIGN Prospect i ve birth cohort study . SETTING Data are taken from the Mater Misericordiae Hospital and University of Queensl and Study of Pregnancy and its outcomes ( MUSP ) , a prospect i ve longitudinal study which recruited women at their first antenatal visit in Brisbane , Australia . PARTICIPANTS A 5- , 14- and 21-year follow-up of children whose mother 's were recruited into the MUSP birth cohort study at their first antenatal visit . MEASUREMENTS Psychopathology exposure was measured using the Achenbach 's Child Behaviour Checklist ( CBCL ) at 5 years , the Youth Self Report ( YSR ) at 14 years and the Young Adult Self Report ( YASR ) at 21 years . Outcome measures were the children 's tobacco smoking status at the 14 and 21 years ' follow-up and the Composite International Diagnostic Interview ( CIDI ) based DSM-IV nicotine dependence at 21 years ' follow-up . FINDINGS Externalizing symptoms had the strongest association with subsequent tobacco use . Children who met the criteria for CBCL aggression at 5 years were more likely to be tobacco smokers at the 14-year follow-up . YSR externalizing behaviours at the 14-year follow-up predicted tobacco smoking , but not DSM-IV nicotine dependence at the 21-year follow-up . Internalizing behaviour ( anxiety/depression ) was associated with a reduced rate of smoking at the 14- and 21-year follow-ups , but externalizing behaviour and attention problems at 14 and 21 years were associated separately and cumulatively with nicotine dependence at the 21-year follow-up . CONCLUSION Childhood and adolescent psychopathology predict tobacco smoking , but some forms of psychopathology predict increased ( aggression/delinquency ; attention problems ) and other forms decreased ( anxiety/depression ) smoking . There may be some benefits in targeting children with early onset aggressive/delinquent behaviour problems with tobacco smoking prevention initiatives CONTEXT Despite the frequent occurrence of depressive symptoms among older adults , especially women , little is known about the long-term course of late-life depressive symptoms . OBJECTIVE To characterize the natural course of depressive symptoms among older women ( from the young old to the oldest old ) followed up for almost 20 years . DESIGN Using latent-class growth-curve analysis , we analyzed women enrolled in an ongoing prospect i ve cohort study ( 1988 through 2009 ) . SETTING Clinic sites in Baltimore , Maryl and ; Minneapolis , Minnesota ; the Monongahela Valley near Pittsburgh , Pennsylvania ; and Portl and , Oregon . PARTICIPANTS We studied 7240 community-dwelling women 65 years or older . MAIN OUTCOME MEASURE The Geriatric Depression Scale short form ( score range , 0 - 15 ) was used to routinely assess depressive symptoms during the follow-up period . RESULTS Among older women , we identified 4 latent classes during 20 years , with the predicted probabilities of group membership totaling 27.8 % with minimal depressive symptoms , 54.0 % with persistently low depressive symptoms , 14.8 % with increasing depressive symptoms , and 3.4 % with persistently high depressive symptoms . In an adjusted model for latent class membership , odds ratios ( ORs ) for belonging in the increasing depressive symptoms and persistently high depressive symptoms classes , respectively , compared with a group having minimal depressive symptoms were substantially and significantly ( P < .05 ) elevated for the following variables : baseline smoking ( ORs , 4.69 and 7.97 ) , physical inactivity ( ORs , 2.11 and 2.78 ) , small social network ( ORs , 3.24 and 6.75 ) , physical impairment ( ORs , 8.11 and 16.43 ) , myocardial infa rct ion ( ORs , 2.09 and 2.41 ) , diabetes mellitus ( ORs , 2.98 and 3.03 ) , and obesity ( ORs , 1.86 and 2.90 ) . CONCLUSIONS During 20 years , almost 20 % of older women experienced persistently high depressive symptoms or increasing depressive symptoms . In addition , these women had more comorbidities , physical impairment , and negative lifestyle factors at baseline . These associations support the need for intervention and prevention strategies to reduce depressive symptoms into the oldest-old years This study employs a prospect i ve design to examine possible personality , drug use , stressful life event , and social support-related variables associated with the onset of a depressive episode in a cohort of psychoactive drug using young adults . Two waves of data , collected one year apart , were available on 942 individuals . Cases ( n = 62 ) were free of depressive symptoms at time 1 but reported significant symptomatology at time 2 as measured by the depression subscale of the Brief Symptom Inventory . Controls ( n = 490 ) were those free of depressive symptoms at both time points . In multivariate analyses , users of the central nervous system depressant methaqualone had a nearly four-fold elevated risk for depressed mood as compared to nonusers . Additional risk factors significant after multivariate adjustment included lower self-esteem at time 1 and negative life events . These results highlight the multifactorial nature of depressive symptomatology We examined prospect ively the association between nicotine dependence and major depression ( MDD ) . The following questions were addressed : ( 1 ) Are smokers with a history of MDD at increased risk for progression to nicotine dependence and more severe levels of dependence ? ( 2 ) Are persons with a history of nicotine dependence at increased risk for MDD ? A sample of 995 young adults were interviewed in 1989 and reinterviewed in 1990 , 14 months later . The revised National Institute of Mental Health-Diagnostic Interview Schedule was used to ascertain DSM-III-R nicotine dependence and other substance use and psychiatric disorders . A history of MDD increased the risk for progression to nicotine dependence or more severe levels of dependence ( odds ratio , 2.06 ; 95 % confidence interval , 1.21 to 3.49 ) . In addition , persons with a history of nicotine dependence had a higher rate of first-incidence MDD during the follow-up period than persons with no history of nicotine dependence ( 7.5 % vs 3.2 % ; odds ratio , 2.45 ; 95 % confidence interval , 1.17 to 5.15 ) . The prospect i ve data suggest that the association between nicotine dependence and MDD , observed previously in cross-sectional studies , might be either causal , with influences flowing in both directions , or , more probably , noncausal , reflecting the effects of common factors that predispose to both disorders BACKGROUND The Children in the Community Study is a prospect i ve longitudinal study investigating the association between early drug use ( childhood , adolescence , and early 20s ) and later psychiatric disorders ( in the late 20s ) . METHODS Using data from a community-based sample of 736 adults ( 50 % female ) from upstate New York , the subjects were interviewed at the mean ages of 14 , 16 , 22 , and 27 years . Psychiatric disorders , measured by age-appropriate versions of the University of Michigan Composite International Diagnostic Interview , and participant 's drug use were assessed . RESULTS Adolescent and young adult tobacco use was significantly associated with an increased risk of alcohol dependence and substance use disorders at a mean age of 27 years , but not with new episodes of major depressive disorder . Earlier alcohol use significantly predicted later major depressive disorder , alcohol dependence , and substance use disorders in the late 20s , as did early marijuana use and other illicit drug use . Except for the effect of tobacco use on major depressive disorder , early drug use was significantly related to later psychiatric disorders , even after statistically controlling for age , sex , parental educational level , family income , and prior episodes of major depressive disorder and substance use disorders . CONCLUSIONS Our results suggest that early drug use is associated with and predicts later psychiatric disorders . Preventive implication s stem from the importance of study ing a range of psychiatric disorders in the context of substance use assessed over a wide age range This report describes a longitudinal study of the natural course of smoking initiation in a school-based , ethnically diverse ( 42 % White , 37 % African American , 20 % Hispanic ) sample of adolescents in grade s 5 , 8 , and 12 who were followed prospect ively for 1 year . A cohort of 659 students was identified who were never smokers at baseline and who completed question naires both at baseline and at 1-year follow-up . From this cohort , predictor variables were used to identify ethnic-specific risk factors for ( a ) " susceptibility to smoking " among the 509 students who were nonsusceptible , never smokers at baseline and ( b ) " ever smoking " among all 659 students who were never smokers at baseline ( both susceptible and nonsusceptible ) . Logistic regression analyses revealed that parental and household influences ( parental education , marital status , household smoking ) were important predictors of ever smoking , but not of susceptibility to smoking , for African Americans . Hispanic adolescents were significantly influenced by environmental influences , namely smoking by other household members ( ever smoking ) and by peers ( susceptibility and ever smoking ) , although peer pro-tobacco influences ( friends who smoke or friends ' approval of smoking ) were important predictors of susceptibility to smoking or ever smoking for all three ethnic groups . Exposure to tobacco-related advertising was a risk factor for White ( susceptibility and ever smoking ) and African American ( susceptibility only ) adolescents but not for Hispanic adolescents . Inclusion of the susceptibility to smoking variable in the model predicting ever smoking substantially reduced the importance of other predictors in the model , suggesting that susceptibility to smoking was not an independent risk factor for ever smoking but rather a potential mediating variable . The results of this study offer important insights for design ing ethnic-specific strategies for preventing smoking during adolescence In 1982‐1983 a r and om sample of 1486 people aged 65 years and above was generated from general practitioner lists ; 1070 were interviewed in the community using the Geriatric Mental State and a Social History question naire . The cohort was followed up by interview 3 years later . At year 3 the diagnostic computer program AGECAT diagnosed 44 incident cases of depression . Information from the depressed group 's initial and further interviews was compared with a control group ( which excluded cases of affective or organic mental illness ) . Univariate analysis yielded three factors that were significantly associated with the development of depression 3 years later : a lack of satisfaction with life ; feelings of loneliness ; and smoking . Multivariate analysis confirmed their independent effects and revealed 2 further factors attaining significance : female gender and a trigger factor , bereavement of a close figure within 6 months of the third‐year diagnosis . Some other factors traditionally associated with depression , such as poor housing , marital status and living alone , failed to attain significance as risk factors This study examined smoking trajectories between adolescence and adulthood in an African American cohort followed prospect ively from first grade to age 32 . We classified non-smokers , former smokers , current smokers/late adopters ( initiated after age 18 ) , and current smokers/early adopters ( initiated before age 17 ) . Results show that almost half of the population were currently smoking . Multiple logistic regression analyses showed that non-smokers differed most from the three smoking groups on social integration . Non-smokers were less likely to have left home before the age of 18 , to have had more drug use parental supervision as an adolescent , to have moved less , and to attend church more frequently as an adult . Those current smokers who initiated early differed from the non-smokers and also from the former smokers and the current smokers who adopted smoking after the age of 18 ; they were more likely to be rated as aggressive or both shy and aggressive by their first grade teachers and to have drug problems as adults . Current smokers were less likely to attend church as adults than the non-smokers and former smokers . Neither mother 's smoking or lifetime depression was related to smoking . The findings eluci date the contribution of factors over the life course that have an impact on smoking initiation , continuation , and cessation . They highlight the importance of targeting African American children and adolescents for prevention despite the fact that African American youth have the lowest rates of smoking across all ethnic groups . Possible interventions could be aim ed at early aggressive behavior , parental supervision and monitoring , and other social integration efforts Objective : The authors used data from a prospect i ve , population -based cohort study to examine : ( a ) whether the presence of chronic bronchitis predicts the subsequent onset of depression or anxiety , and ( b ) if the incidence of depressed or anxious cases was different for smokers compared with nonsmokers . Material s and Methods : For study ing the relation between chronic bronchitis and anxiety or depression , we used data from respectively 4468 and 4520 respondents . Results : The number of incident anxious ( 19.1 % , n = 17 ) and depressed ( 14.0 % , n = 13 ) cases was highest in employees with chronic bronchitis compared with employees without respiratory complaints ( 4.3 % , n = 189 and 3.3 % , n = 145 , respectively ) . The presence of chronic bronchitis was associated with a significant increase in anxious and depressed cases ( odds ratio ( OR ) for anxiety = 5.09 , 95 % confidence interval ( CI ) 2.91 , 8.89 ; OR for depression = 4.38 , 95 % CI 2.35 , 8.16 ) . The incidence of anxiety as well as depression was strongest in the smokers group ( OR for anxiety = 8.94 , 95 % CI 4.08 , 19.59 ; OR for depression = 7.56 , 95 % CI 3.37 , 16.96 ) . Conclusions : This prospect i ve study shows significantly higher levels of anxiety as well as depression in employees with chronic bronchitis . Results also seem to indicate that smoking cigarettes modifies this association , result ing in an increased risk of depression and anxiety in employees with chronic bronchitis who smoke . COPD = chronic obstructive pulmonary disease ; HADS = Hospital Anxiety and Depression Scale ; HADS-A = HADS anxiety subscale ; HADS-D = HADS depression subscale OBJECTIVE Early onset of smoking is associated with subsequent abuse of other substances and development of negative health outcomes . This study aim ed to examine early life predictors of onset of smoking in an Australian young cohort . METHODS Data were from the Mater Hospital and University of Queensl and Study of Pregnancy ( MUSP ) , a population -based prospect i ve birth cohort study ( 1981 - 2012 ) . The present study is based on a cohort of 3714 young adults who self-reported smoking status and age of onset of smoking at the 21-year follow-up . Of these , data were available for 3039 on early childhood factors collected between the baseline and 14-year follow-up of the study . RESULTS Of 3714 young adults , 49.6 % ( 49.9 % males and 49.3 % females ) reported having ever smoked cigarettes . For those who had ever smoked , mean and median ages at first smoke were 15.5 and 16.0years , respectively . In multivariate Cox proportional hazard analysis mother 's education , change in maternal marital status , maternal cigarette smoking and alcohol consumption , maternal depression and child externalizing when the child was 5years statistically significantly predicted early onset of smoking . CONCLUSIONS The data suggest that individuals exposed to personal and environmental risk factors during the early stage of childhood are at increased risk of initiation to cigarette smoking at an earlier age . Identification of the pathways of association between these early life factors and initiation to cigarette smoking may help reduce risk of tobacco smoking in adolescents and its adverse consequences This study examined whether sixth- grade rs ' depressed mood and positive substance use expectancies predicted increases over the next two years in students ' lifetime and 30-day cigarette , alcohol , and marijuana use , and whether sixth grade rs ' positive substance use expectancies moderated the relationship between baseline depressed mood and changes over the next two years in the use of these substances . Study data came from a r and omized controlled trial of Project ALERT , a school-based substance use prevention program , in which students from 34 schools completed self-report surveys as sixth ( n=5782 ) , seventh ( n=5065 ) , and eighth grade rs ( n=4940 ) . Primary analyses were performed using Hierarchical Nonlinear Modeling . Over time , there were significant effects of baseline positive expectancies on each of the six measures of substance use . Baseline depressed mood predicted increases over time only for lifetime use of cigarettes and alcohol , and for 30-day alcohol use . Positive expectancies significantly moderated the effects of adolescent depressed mood only on lifetime marijuana use . Although depressed mood predicted substance use for half of our variables , our results suggest that positive expectancies are a more consistent predictor of adolescent substance use , and that they may moderate the effects of depressed mood on marijuana , but not cigarette or alcohol , use . Substance use prevention programs may benefit from addressing adolescents ' perceptions about the positive consequences of drug use BACKGROUND A large number of adults report symptoms of , but do not meet diagnostic criteria for , an alcohol use disorder . Yet , little is known about the relationship between symptoms of alcohol use disorders and the initiation and persistence of smoking . This study prospect ively examines the relationship between having 1 - 2 symptoms of alcohol dependence ( without abuse ) and smoking initiation and persistence as well as nicotine dependence over a 3-year period among adults in the United States . METHODS Data were drawn from Wave 1 ( 2001 - 2002 ) and Wave 2 ( 2004 - 2005 ) of the National Epidemiologic Survey on Alcohol and Related Conditions . Relationships between Wave 1 symptoms of alcohol dependence , alcohol abuse , and alcohol dependence and initiation and persistence of cigarette smoking and nicotine dependence at Wave 2 were examined using logistic regression analyses . Analyses were adjusted for demographics , mood and anxiety disorders . RESULTS Symptoms of alcohol dependence were associated with smoking initiation at Wave 2 . There was no association between symptoms of alcohol dependence and smoking persistence . Symptoms of alcohol dependence predicted incident and persistent nicotine dependence . Findings persisted after adjusting for demographic characteristics and mood/anxiety disorders . CONCLUSIONS Even 1 - 2 symptoms of alcohol dependence are associated with increased vulnerability to smoking initiation and onset and persistence of nicotine dependence at a similar strength as alcohol use disorders . Efforts at smoking cessation must address problematic alcohol use , even at the sub clinical level , in order to improve efficacy Previous studies have found that constituents in tobacco inhibit both forms of the enzyme monoamine oxidase ( MAO-A and MAO-B ) . This enzyme is important in the breakdown of the amine neurotransmitters , including dopamine , which is thought to mediate the reinforcing effects of nicotine and contribute to tobacco dependence . To further examine the relationship between cigarette smoking , smoking cessation and MAO , we measured platelet MAO-B activity in 16 smokers before and after being switched to smoking denicotinized cigarettes ; in a subset of six subjects who subsequently quit-smoking , MAO-B activity was also measured at 1 and 4 weeks following cessation . Smoking cessation treatment was provided in an open-label format , and included nicotine skin patch treatment in conjunction with oral mecamylamine ( a nicotinic antagonist ) and neostigmine ( a peripherally acting acetylcholinesterase inhibitor , administered to counteract constipation experienced from mecamylamine ) . Results showed that smoking behavior , indexed by expired air carbon monoxide levels , was negatively correlated with platelet MAO-B activity prior to smoking cessation . Moreover , MAO-B activity significantly increased by approximately 100 % at 4 weeks after quitting smoking . However , little or no recovery occurred within the first week of abstinence , suggesting that the constituents in tobacco responsible for MAO inhibition may have half-lives of several days . Thus , if relapse to smoking is due in part to withdrawal from the MAO-inhibiting effects of tobacco , this effect likely occurs more than 1 week after quitting . Additionally , low baseline MAO-B activity significantly predicted the intensity of withdrawal symptoms reported upon switching to the denicotinized cigarettes as well as after smoking cessation . These results support the view that MAO inhibition from non-nicotine constituents in cigarette smoke is relevant to tobacco dependence and that continued investigation of the potential use of MAO inhibitors in smoking cessation treatment is warranted Context . Although several risk factors for tobacco use have been implicated in the development of depression , smoking progression has typically been viewed as a consequence of depression . The results of limited longitudinal studies are controversial . Objective . To assess the nature and direction of the relationship between cigarette smoking and depression among teens . Design . Prospect i ve analysis of baseline and 1-year follow-up data from the National Longitudinal Study of Adolescent Health . Setting . In-home teen and parent interviews . Participants . Two sample s were identified . For the first sample , 8704 adolescents who were not depressed at baseline based on CES-D scores were identified for analyses of the effects of cigarette smoking on development of high depressive symptomatology . Baseline smoking status , which could vary in this group , was the predictor of interest in these analyses . For the second sample , 6947 teens who had not smoked cigarettes in the 30 days before the baseline survey ( noncurrent smokers ) were identified for analyses on the effect of high depressive symptoms on subsequent moderate to heavy cigarette use at 1 year of follow-up . Baseline high depressive symptomatology based on CES-D score was the predictor of interest in this sample . Main Outcome Measures . Among the nondepressed , developing high depressive symptoms at 1 year of follow-up . Among noncurrent smokers , smoking at least 1 pack per week at 1 year of follow-up . Results . For the nondepressed , multivariate modeling revealed that current cigarette smoking was the strongest predictor of developing high depressive symptoms in all models ( final model odds ratio [ OR ] : 3.90 ; 95 % confidence interval [ CI ] : 1.85,8.20 ) . For noncurrent smokers , although in bivariate analyses , baseline high depressive symptoms increased the risk of heavy smoking nearly threefold , multivariate modeling revealed that baseline high depressive symptoms were not predictive of heavy smoking when controlling for other determinants of smoking in teens . Previous experimentation with smoking was the strongest predictor of becoming a heavy smoker ( OR : 3.04 ; 95 % CI : 1.93,4.88 ) . Conclusions . In contrast to common dictum , depression does not seem to be an antecedent to heavy cigarette use among teens . However , current cigarette use is a powerful determinant of developing high depressive symptoms BACKGROUND Recent cross-sectional studies suggest some adolescents who have never smoked cigarettes experience nicotine dependence ( ND ) symptoms and that exposure to second-h and smoke , social exposure to smoking , and alcohol use are plausible correlates . The aim of this study was to replicate and extend these findings by investigating possible predictors of ND symptoms longitudinally . METHOD Participants included 847 secondary school students who had never smoked cigarettes enrolled in the Nicotine Dependence in Teens Study . Adolescents completed self-report question naires measuring smoking status , ND symptoms , and risk factors for ND in smokers ( i.e. , socio-demographic indicators , social exposure to smoking , psychosocial indicators , and substance use ) in 20 survey cycles from 7 to 11th grade . Generalized estimating equations , which account for repeated measures within individuals , were used to test the predictors of ND symptoms . RESULTS Consistent with previous research , 7.8 % of never-smokers across all cycles endorsed at least one ND symptom . Younger age ( p ≤ .001 ) , country of birth ( p ≤ .05 ) , peer smoking ( p ≤ .001 ) , teacher smoking ( p ≤ .05 ) , depression ( p ≤ .05 ) , stress ( p ≤ .001 ) , lower self-esteem ( p ≤ .05 ) , impulsivity ( p ≤ .05 ) , and alcohol use ( p ≤ .001 ) predicted greater ND symptoms in multivariable modeling . CONCLUSIONS Replicating previous cross-sectional findings , peer smoking and alcohol use predicted ND symptoms among never-smoking adolescents . Extending these findings , previous predictors only observed among ever-smokers , including socio-demographic and psychosocial indicators , also predicted ND symptoms . This longitudinal investigation demonstrated the temporal relation of the predictors preceding ND symptoms . Future research should consider longer prospect i ve studies with younger children to capture early onset of ND symptoms and with longer follow-up to detect eventual smoking uptake Adolescence is an important period for initiation of smoking and manifestation of depression , which are often comorbid . Research ers have examined associations between depressive symptoms and smoking to eluci date whether those with increased depressive symptoms smoke more to self-medicate , whether those who smoke experience increased subsequent depressive symptoms , or both . Collectively , there have been mixed findings ; however , studies have been limited by ( 1 ) cross-sectional or short-term longitudinal data or ( 2 ) the use of methods that test associations , or only one direction in the associations , rather than a fully-reciprocal model to examine directionality . This study examined the associations between smoking and depressive symptoms in a sample of adolescent girls using latent dual change scores to model ( 1 ) the effect of smoking on change in depressive symptoms , and simultaneously ( 2 ) the effect of depressive symptoms on change in smoking across ages 11–20 . Data were from a cohort-sequential prospect i ve longitudinal study ( N = 262 ) . Girls were enrolled by age cohort ( 11 , 13 , 15 , and 17 years ) and were primarily White ( 61 % ) or African American ( 31 % ) . Data were restructured by age . Every 6 months , girls reported depressive symptoms and cigarette use . Results indicated that controlling for sociodemographic characteristics , higher levels of smoking predicted a greater increase in depressive symptoms across adolescence . These findings suggest that a higher level of cigarette smoking does contribute to more depressive symptoms , which has implication s for prevention of depression and for intervention and future research AIMS Young adulthood represents a period of continued smoking progression and the establishment of regular and long-term smoking practice s. Our underst and ing of the psychological processes that facilitate and solidify regular smoking patterns in this developmental period is limited . We sought to evaluate the role of depression symptoms in young adult smoking uptake and to evaluate whether non-smoking related alternative reinforcers was a mechanism by which depression symptoms influence smoking . PARTICIPANTS The sample was composed of 834 young adults who participated in a longitudinal study of smoking adoption ( aged 18 - 22 years ) . DESIGN AND MEASUREMENTS In this prospect i ve cohort study , smoking , depression , alternative reinforcers and several covariates were measured annually via telephone from emerging adulthood ( age 18 ) to young adulthood ( age 22 ) . FINDINGS Results of a parallel processes latent growth curve model showed that depression symptoms level ( baseline age 18 ) had a significant negative effect on substitute alternative reinforcers trend ( β = -0.01 , Z = -3.17 , P=0.002 ) and that substitute reinforcers trend had a significant negative effect on smoking trend ( β = -0.62 , Z = -2.99 , P = 0.003 ) . An assessment of indirect effects revealed that depression symptoms level had a significant positive indirect effect on smoking trend through substitute alternative reinforcers trend ( β = 0.01 , Z = 2.09 , P = 0.04 , 99 % CI = 0.001 , 0.02 ) , such that greater depression symptoms at baseline predicted decreases in substitute reinforcers across time which in turn predicted increases in smoking uptake/rate from emerging to young adulthood . CONCLUSIONS Depressive symptoms in emerging adulthood appear to influence smoking uptake and smoking rate through reductions in alternative reinforcers . This suggests that increasing involvement in alternative reinforcers may prevent smoking uptake and escalation in smoking rate Objective : To study the incidence of conversion to tobacco dependence ( TD ) and the prevalence of the TD state in relation to several potential determinants in a sample of adolescent smokers . Methods : Question naires were administered every 3–4 months to document TD symptoms , amount of cigarette consumption , and depression symptoms in a prospect i ve cohort of 1293 grade 7 students in a convenience sample of 10 schools . Results : Over 54 months of follow-up , 113 of 344 novice smokers converted to TD . The referent series for the analysis of incidence comprised 823 person-surveys . The prevalence series included 1673 person-surveys , contributed by 429 smokers . Conversion to TD and TD status were associated with the intensity of recent ( that is , past 3-month ) cigarette consumption ( adjusted incidence rate ratio ( aIRR ) 1.63 ( 95 % confidence interval ( CI ) 1.36 to 1.97 ) and adjusted prevalence odds ratio ( aPOR ) 1.35 ( 95 % CI 1.23 to 2.48 ) per 100 cigarettes per month ) , slowest CYP2A6 activity ( aIRR 4.19 ( 95 % CI 1.38 to 12.76 ) and aPOR 2.30 ( 95 % CI 1.29 to 4.09 ) ) , depression score ( aIRR 1.61 ( 95 % CI 1.17 to 2.21 ) and aPOR 1.47 ( 95 % CI 1.22 , 1.75 ) per 1-unit change ) . Additional determinants included , for conversion to TD , time since onset of cigarette use ( aIRR 0.76 ( 95 % CI 0.58 to 1.00 ) per year ) and , for the TD state , positive TD status six months ago ( aPOR 3.53 ( 95 % CI 2.41 to 5.19 ) ) . Conclusions : TD risk in adolescents is associated with intensity of recent cigarette consumption , while the role of more distant cigarette consumption appears small ; subjects with slow nicotine metabolism and those with more depression symptoms are at increased risk of becoming tobacco dependent . The risk of being tobacco dependent is considerably higher in subjects who had previously developed the TD state Few prospect i ve studies of smoking initiation have investigated a wide range of time-varying and invariant predictor variables at the individual and context ual levels concurrently . In this study ( 1999 - 2005 ) , 877 Canadian students ( mean age = 12.7 years ) who had never smoked at baseline completed self-report question naires on cigarette smoking and 32 predictor variables in 20 survey cycles during secondary school . Height and weight were measured in survey cycles 1 , 12 , and 19 . School administrators completed question naires on school tobacco control policies/activities , and trained observers collected data on access to tobacco products in commercial establishments near schools . Younger age , single-parent family status , smoking by parents , siblings , friends , and school staff , stress , impulsivity , lower self-esteem , feeling a need to smoke , not doing well at school , susceptibility to tobacco advertising , alcohol use , use of other tobacco products , and attending a smoking-tolerant school were independent determinants of smoking initiation . Independent determinants of daily smoking onset among initiators of nondaily smoking included smoking by siblings and friends , feeling a need to smoke , susceptibility to tobacco advertising , use of other tobacco products , and self-perceived mental and physical addiction . Adolescent tobacco control programs should address multiple individual and context ual-level risk factors . Strategies that address nicotine dependence symptoms are also needed for adolescents who have already initiated smoking Objective : Depression occurs comorbidly in patients hospitalized for a range of cardiac conditions and procedures . This study examines the fluctuations in depressive symptomatology from index hospitalization to 3 months after hospitalization and determines predictors of depression 3 months after hospital admission for a cardiac condition or procedure . Methods : Baseline clinical and demographic variables collected from a prospect i ve study of the natural history of depression in 833 hospitalized cardiac patients were entered into a multinomial regression analysis . Results : Similar proportions of participants were found to have no , mild , or moderate to severe depression at baseline and at 3 months , although 35.8 % of participants had moved from one depression level to another during that period . Baseline characteristics predicting depression at 3 months after hospitalization were : a mild or moderate to severe level of depressive symptoms at hospitalization ; younger age ; smoking ; self-reported previous diagnosis of a cardiac condition ; and self-reported history of depression , anxiety , or stress . Conclusions : The five clinical ly accessible variables identified as predictors in this study may assist physicians in identification of cardiac patients who are at risk of persistent depression and who may require active intervention . Given that depression in cardiac patients is related to increased mortality and morbidity and that it is currently poorly diagnosed , these findings may have implication s for preventing adverse outcomes The purpose of this longitudinal , prospect i ve study was to evaluate trajectories of smoking in a cohort of African-American and Puerto Rican young adults and describe personality and behavioral factors associated with specific smoking trajectory group membership . Participants consisted of African-American and Puerto Rican male and female young adults ( N = 451 , mean age 26 ) from an inner-city community . Data were collected at four time points over a period of 13 years using structured interviews . Interviews took place within the schools and the participants ' homes . Scales with adequate psychometric properties were adapted from previously vali date d measures . Variables that were examined for this study came from the domains of internalizing behaviors , externalizing behaviors , drug use , and demographic information . Data were analyzed using latent growth mixture modeling to explore discrete smoking trajectories . Logistic regression analyses were then used to examine the risk factors associated with the various smoking trajectory groups . Four trajectory groups were determined to best fit the data : nonsmokers , maturing-out smokers , late-starting smokers , and early-starting continuous smokers . Subjects who were unconventional , experienced intrapersonal distress , and used alcohol and illegal drugs were more likely to belong to one of the smoking trajectory groups than to the nonsmoking group . The early-starting continuous group scored highest on these personal risk attributes . The long-term impact of unconventional behavior , intrapersonal distress , and drug use on developmental trajectories of smoking support the importance of early intervention and prevention Constructs representative of global positive expectancies ( GPE ) such as dispositional optimism and hope have been theoretically and empirically linked to many positive mental and physical health outcomes . However such expectancies ’ health implication s for adolescents , as well as their trajectory over time , are less well understood than for adult population s. This study tested whether GPE predict the key indicators of adolescents ’ future physical health status , their health-related behaviours . A prospect i ve longitudinal study design was employed whereby a diverse population -based cohort ( N = 744 ; mean age at baseline = 12 ) completed three surveys over approximately 18 months . Rigorous tests of causal predominance and reciprocal effects were conducted through latent growth and cross-panel structural equation models . Results showed GPE systematic ally decreased during the course of the study , yet higher initial levels of GPE predicted less alcohol drinking , healthier food choice and greater physical activity over time . GPE 's protective relationships towards health protective behaviours ( vs. health risk behaviours that also included tobacco smoking ) appear more independent from depressive symptomatology , and the primary findings were robust across socio-demographic groups Children of parents with substance use disorders ( SUDs ) have been shown to demonstrate an increased risk for cigarette smoking in adolescence . In this prospect i ve study , we hypothesized that adolescent cigarette smoking risk would be accounted for by childhood disruptive behavior disorders and parent cigarette smoking . Preadolescent children ( ages 10 - 12 years ) of fathers with SUD considered at high average risk ( HAR ; n=274 ) and children of fathers without SUD or major psychopathology considered at low average risk ( LAR ; n=298 ) participated in structured interviews to determine mental disorder diagnoses and substance use history . Both parents were assessed . The age of onset of daily tobacco use was determined in three follow-up assessment s conducted through late adolescence . Conduct disorder ( CD ) and parental smoking predicted earlier daily cigarette smoking , and mediated the relationship between risk status and offspring daily cigarette smoking . Through the identification of childhood characteristics predicting daily cigarette smoking in adolescence , these results may facilitate targeting of early childhood preventive interventions AIMS To investigate prospect ively the associations between daily smoking and nicotine dependence and anxiety , depression and suicide attempts . METHODS Data were from the Young in Norway Longitudinal Study . A population -based sample ( n = 1501 ) was followed for 13 years from ages 13 - 27 years . Data were gathered on smoking patterns and nicotine dependence ; and depression , anxiety and parasuicide . Extensive information on socio-demographic factors , parental and family conditions , parental rearing practice s , educational career , conduct problems , alcohol problems and use of illegal substances was also collected . RESULTS Young adults who were nicotine-dependent had clearly elevated rates of anxiety , depression and parasuicide . These rates declined after controlling for a previous history of mental health problems and potential confounding factors . After adjustment , nicotine dependence was still associated with anxiety , depression and parasuicide . There was also a significant association with later depression in the group of non-dependent daily smokers . Measures of reduced mental health did not predict later smoking initiation or the development of nicotine dependence . CONCLUSIONS Mental health was reduced more seriously in nicotine-dependent smokers than in non-dependent smokers . These findings are consistent with the hypothesis that smoking , in particular nicotine dependence , influences mental health AIMS To examine whether physical health and health-risk behaviours in young people are risk factors for psychological distress and depressive symptoms over a 2-year period . DESIGN / SETTING A 2-year , prospect i ve epidemiological cohort study in East London . PARTICIPANTS A total of 1615 adolescents from the Research with East London Adolescents : Community Health Survey (RELACHS)-a representative cohort of young people aged 11 - 12 and 13 - 14 years at baseline , followed-up after 2 years . MEASUREMENTS Psychological distress and depressive symptoms identified by the self-report Strengths and Difficulties Question naire and the Short Moods and Feelings Question naire at baseline and follow-up . Data on overweight/obesity , general health , long-st and ing illness , physical activity , smoking , alcohol use and drug use were collected from question naires completed by the adolescents at baseline and follow-up . FINDINGS At follow-up , 10.1 % of males and 12.9 % of females reported psychological distress ; 20 % of males and 33.7 % of females reported depressive symptoms . Having tried drugs or engaged in two or more health-risk behaviours ( smoking , alcohol use or drug use ) at baseline predicted psychological distress and depressive symptoms at follow-up . Smoking on its own , long-st and ing illness , obesity/overweight and activity levels were not associated with later psychological health . Risk of poor psychological health at follow-up was associated strongly with psychological health at baseline . CONCLUSIONS Psychological health at baseline was the strongest predictor of psychological health at follow-up . Engaging in two or more health-risk behaviours moderately increased the risk of poor psychological health , suggesting that prevention strategies targeting co-occuring substance use may reduce burden of disease Among 1566 personally evaluated female twins from a population -based register , average lifetime daily cigarette consumption was strongly related to lifetime prevalence and to prospect ively assessed 1-year prevalence of major depression ( MD ) . Using the cotwin control method , we evaluated whether the association between smoking and lifetime MD was causal or noncausal . While the relative risk ( 95 % confidence interval ) for ever smoking given a lifetime history of MD was 1.48 ( 1.30 to 1.65 ) in the entire sample , it was 1.18 ( 0.88 to 1.47 ) and 0.98 ( 0.71 to 1.26 ) , respectively , in dizygotic and monozygotic twin pairs discordant for a history of MD . The relative risk for a history of MD given ever smoking was 1.60 ( 1.39 to 1.83 ) in the entire sample , while in dizygotic and monozygotic twins discordant for smoking , it was 1.29 ( 0.87 to 1.74 ) and 0.96 ( 0.59 to 1.42 ) , respectively . Controlling for personal smoking history , family history of smoking predicted risk for MD ; controlling for the personal history of MD , family history of MD predicted smoking . The best-fitting bivariate twin model suggested that the relationship between lifetime smoking and lifetime MD result ed solely from genes that predispose to both conditions . These results suggest that the association between smoking and MD in women is not a causal one but arises largely from familial factors , which are probably genetic , that predispose to both smoking and MD BACKGROUND Some evidence suggests that depression may increase the risk of adult-onset asthma . No data are available for African American women , in whom the prevalence of depression and asthma is high . OBJECTIVE To conduct prospect i ve analyses of the relation of depressive symptoms to asthma incidence in the Black Women 's Health Study , a prospect i ve cohort of US black women followed since 1995 with mailed biennial question naires . METHODS Of 31,848 participants followed from 1999 to 2011 , 771 reported incident asthma . Depressive symptoms were ascertained on 1999 and 2005 follow-up question naires with the Center for Epidemiological Studies -Depression Scale ( CES-D ) . Participants rated the frequency of 20 symptoms . A score was calculated by summing the responses to all questions . Cox regression models were used to derive incidence rate ratios and 95 % confidence intervals for 4 categories of the CES-D score in relation to incident asthma , adjusted for body mass index , smoking , and other covariates . RESULTS The multivariable incidence rate ratio in the highest category of CES-D score ( ≥ 33 ) compared with the lowest ( < 16 ) was 2.08 ( 95 % confidence interval 1.58 - 2.74 ) , with a significant trend ( P < .0001 ) . The incidence rate ratio was higher in women who took antidepressants , were current or former smokers , were not obese , and were at least 40 years old , although there were no statistically significant interactions . CONCLUSION A positive association was observed between CES-D score and the incidence of adult-onset asthma . If the hypothesis is confirmed , depression could contribute substantially to the burden of asthma in adults AIMS The nature of the relationship between adolescent smoking and depression is unclear and the mechanisms that account for the comorbidity have received little investigation . The present study sought to clarify the temporal precedence for smoking and depression and to determine whether these variables are linked indirectly through peer smoking . PARTICIPANTS The sample was composed of 1093 adolescents participating in a longitudinal study of the behavioral predictors of smoking adoption . DESIGN AND MEASUREMENTS In this prospect i ve cohort study , smoking , depression , peer smoking and other covariates were measured annually from mid-adolescence ( 9th grade ; age 14 ) to late adolescence ( 12th grade , age 18 ) . FINDINGS Parallel processes latent growth curve models supported a bidirectional relationship between adolescent smoking and depression , where higher depression symptoms in mid-adolescence ( age 14 ) predicted adolescent smoking progression from mid- to late adolescence ( ages 14 - 18 ) . A significant indirect effect indicated that higher depression symptoms across time predicted an increase in the number of smoking peers , which in turn predicted smoking progression from mid-adolescence to late adolescence . In addition , smoking progression predicted a deceleration of depression symptoms from mid- to late adolescence . A significant indirect effect indicated that greater smoking at baseline predicted a deceleration in the number of smoking peers across time , which predicted a deceleration in depression symptoms from mid-adolescence to late adolescence . CONCLUSIONS The current study provides the first evidence of bidirectional self-medication processes in the relationship between adolescent smoking and depression and highlights peer smoking as one explanation for the comorbidity AIMS To examine the association of adolescent depression and anxiety symptoms with daily smoking and nicotine dependence in young adulthood . DESIGN A prospect i ve cohort study of adolescent and young adult health ( n = 1943 ) . Teen assessment s occurred at 6-monthly intervals , with two follow-up assessment s in young adulthood ( wave 7 , 1998 ; wave 8 , 2001 - 03 ) . SETTING Victoria , Australia . Participants Students who participated at least once during the first six ( adolescent ) waves of the cohort study . MEASUREMENTS Adolescent depression and anxiety symptoms were assessed using the Revised Clinical Interview Schedule ( CIS-R ) . Young adult tobacco use was defined as : daily use ( 6 or 7 days per week ) and dependent use ( > or = 4 on the Fagerstrom Test for Nicotine Dependence ) . FINDINGS Among adolescent ' less than daily ' smokers , those with high levels of depression and anxiety symptoms had an increased risk of reporting nicotine dependence in young adulthood [ odds ratio ( OR ) 3.3 , 95 % confidence interval ( CI ) 1.2 - 9.1 ] compared to young adults who had low levels of adolescent depression and anxiety symptoms , after adjusting for potential confounding factors . Similarly , in the adjusted model ( OR 1.9 , 95 % CI 1.0 - 3.4 ) , among adolescent ' daily ' smokers , those with high levels of depression and anxiety symptoms had an almost two-fold increase in the odds of reporting nicotine dependence in young adulthood compared to young adults with low levels of adolescent depression and anxiety symptoms . CONCLUSIONS Adolescent smokers with depression and anxiety symptoms are at increased risk for nicotine dependence into young adulthood . They warrant vigilance from primary care providers in relation to tobacco use well into adulthood OBJECTIVE To examine prospect ively the comorbidity of DSM-IV psychiatric disorders and nicotine dependence in adolescence . METHOD A multiethnic sample ( N = 1,039 ) of adolescents from grade s 6 to 10 in the Chicago public schools ( mean age 14.1 years ) was interviewed at home five times , and mothers were interviewed three times over a 2-year period ( 2003 - 2005 ) . Completion rates at each wave were 96 % of the initial sample . Selected DSM-IV psychiatric disorders were ascertained from youths and mothers about youths at two annual waves with the NIMH Diagnostic Interview Schedule for Children , Version IV-Y and IV-P ; DSM-IV symptoms of nicotine dependence were ascertained from youths at every wave using a measure developed for adolescents . RESULTS Psychiatric disorders most often preceded the onset of the first criterion of nicotine dependence . Prospect i ve associations between psychiatric disorders and nicotine dependence were examined through logistic regressions . After controlling for comorbid disorders , it was found that lifetime disruptive disorder significantly predicted the onset of a nicotine dependence criterion ( adjusted odds ratio 2.1 ) . Early onset of any psychiatric disorder increased this risk . Other predictors included novelty seeking and extensiveness of smoking . By contrast , nicotine dependence did not predict the onset of a psychiatric disorder ; significant predictors included the youths ' prior other psychiatric disorders , novelty seeking , and parental depression and antisocial behavior . CONCLUSIONS Nicotine dependence does not seem to contribute to the onset of psychiatric disorders , whereas disruptive disorder is an important etiologic factor for nicotine dependence in adolescence |
1,241 | 24,555,766 | In conclusion , this meta- analysis suggests that the addition of r-hLH to r-hFSH may be beneficial for women with POR | Background The potential benefit of adding recombinant human luteinizing hormone ( r-hLH ) to recombinant human follicle-stimulating hormone ( r-hFSH ) during ovarian stimulation is a subject of debate , although there is evidence that it may benefit certain sub population s , e.g. poor responders . | PURPOSE The purpose of this prospect i ve , r and omized study was to compare ovarian response and oocyte and embryo yields in women undergoing ovulation induction for IVF/ICSI using recombinant human FSH ( rhFSH ) alone or in combination with recombinant human LH ( rhLH ) . METHODS Patients were r and omized to receive rhFSH alone ( group F ; n = 13 ) or rhFSH + rhLH ( group L ; n = 15 ) . rhFSH was administered according to a step-down protocol ; patients assigned to group L received rhLH at a fixed dose of 75 IU ( 1 ampoule ) throughout the treatment period . RESULTS The total dose of rhFSH , number of growing follicles , and serum concentrations of estradiol ( E2 ) on the day of hCG administration were similar in both treatment groups . However , the percentage of metaphase II oocytes and fertilization rate were significantly higher in group F than in group L. The lower fertilization rates associated with rhLH were also seen in a subgroup of patients from group L who had undergone a previous ART cycle stimulated with FSH only and thus acted as their own controls . However , when in vitro fertilization ( IVF ) and intracytoplasmic sperm injection cycles were considered separately , differences in fertilization rates were statistically significant only for oocytes treated by conventional IVF . CONCLUSIONS This study shows that the addition of recombinant LH to recombinant FSH in pituitary-suppressed women undergoing ART does not improve the ovarian response and even may have a negative impact on oocyte maturation and fertilization OBJECTIVE To evaluate the effects of recombinant human luteinizing hormone ( rhLH ) supplementation on ovarian stimulation and implantation rate in down-regulated women of advanced reproductive age . DESIGN Prospect i ve r and omized study . SETTING University teaching hospital . PATIENT(S ) A total of 120 consecutive normogonadotropic infertile women > or = 35 years old undergoing their first cycle of IVF or intracytoplasmic sperm injection ( ICSI ) treatment . INTERVENTION(S ) Ovarian stimulation in a long agonist protocol with a combination of recombinant human follicle-stimulating hormone ( rhFSH ) and rhLH ( group 1 , n = 60 ) starting on day 6 of FSH stimulation until hCG at a daily fixed dose of 150 IU of rhLH , or with rhFSH alone ( group 2 , n = 60 ) . MAIN OUTCOME MEASURE(S ) Ovarian stimulation characteristics , ovum retrieval , and IVF/ICSI outcome . RESULT ( S ) The mean number of intermediate ( 10 - 14 mm ) and large ( > 14- < 18 mm ) but not leading ( > or = 18 mm ) follicles was significantly lower in group 1 on the day of hCG injection . The oocyte yield and maturity as well as the number of oocytes fertilized were significantly higher in group 2 than in group 1 . However , the number of patients having embryo transfer ( n = 55 in both treatment groups ) , the number and quality of embryos replaced , the implantation rate ( 20.6 % vs. 21.7 % ) and clinical pregnancy rates per embryo transfer ( 44 % vs. 45 % ) were similar in groups 1 and 2 . CONCLUSION ( S ) The rhLH supplementation does not increase ovarian response and implantation rates in patients of older reproductive age stimulated with rhFSH under pituitary suppression for assisted reproductive technologies ( ARTs ) Women undergoing intracytoplasmic sperm injection ( ICSI ) for male factor infertility were r and omly assigned to receive ovarian stimulation in a long agonist protocol with a combination of recombinant human FSH ( r-hFSH ; Gonal-F ) and recombinant human LH ( r-hLH ; Luveris ) ( n = 212 ) starting on day 6 of FSH stimulation until human chorionic gonadotrophin ( HCG ) at a daily fixed dose of 150 IU r-hLH , or with r-hFSH alone ( n = 219 ) . There was no significant difference in the number of metaphase II oocytes retrieved ( 10.3 versus 10.4 ) in patients treated with r-hFSH and r-hLH versus r-hFSH alone ; however , more embryos were transferred in the LH-supplemented group ( 2.9 versus 2.8 , P = 0.037 ) . Overall , the implantation rates were 22.9 versus 27.0 % in patients treated with r-hFSH and r-hLH versus with r-hFSH alone respectively ( NS ) . The respective numbers of MII oocytes retrieved in patients < 35 or > or=35 years were 11 versus 8.3 ( P = 0.010 ) for patients treated with r-hFSH alone , and 10.7 versus 9.3 ( NS ) for those given supplemental r-hLH ( 150 IU ) from day 6 . Implantation rates in patients < 35 years treated with r-hFSH were higher ( 30.7 % ) than those receiving r-hFSH and r-hLH , ( 23.5 % ) ( P = 0.068 ) . In patients > or=35 years , the implantation rates were 21.7 % for those patients supplemented with 150 IU r-hLH from day 6 of stimulation versus 15.7 % when treated with FSH alone ( NS ) . Younger patients therefore do not seem to benefit from an LH-supplemented ovarian stimulation protocol , but women > or=35 years undergoing assisted reproduction may benefit from using r-hLH in addition to r-hFSH BACKGROUND Poor ovarian response is a common clinical problem , affecting up to 26 % of IVF cycles . For these women , addition of recombinant luteinizing hormone ( rLH ) to ovarian hyperstimulation with recombinant FSH has a beneficial effect on ongoing pregnancy rates , but its effect on the yield of top- quality embryos is unknown . METHODS We conducted a r and omized controlled trial in women expected to respond poorly under ovarian hyperstimulation during their first IVF cycle [ all women aged 35 - 41 and women with FSH > 12 IU/ml and antral follicle count ( AFC ) ≤ 5 ] . Women were r and omly allocated to rFSH and rLH ( 2:1 ratio ) or rFSH alone ( control group ) after down-regulation with a GnRH agonist . The primary outcome was the proportion of top- quality embryos per woman on the day of transfer . Secondary outcomes were the number of stimulation days , the number of follicles ≥17 mm , the number of oocytes , the fertilization rate , the number of embryos , the number of women with ≥1 top- quality embryo , the biochemical , clinical and ongoing pregnancy rates and the miscarriage rate . RESULTS There were 116 women allocated to the rLH group and 128 allocated to the control group . The proportion of top- quality embryos per woman was 17 % in the rLH group and 11 % in the control group [ mean difference 0.06 ; 95 % confidence interval ( CI ) -0.01 - 0.14 ] . In the rLH and control groups respectively , 47 ( 41 % ) and 41 ( 32 % ) women had at least one top- quality embryo on the day of transfer ( relative risk : 1.3 , 95 % CI 0.91 - 1.77 ) . The ongoing pregnancy rate was 13 versus 12 % ( relative risk : 1.1 ; 95 % CI 0.57 - 2.16 ) for the rLH group compared with the control group . CONCLUSIONS This study found no significant difference in embryo quality after the addition of rLH to rFSH for ovarian stimulation in women with poor ovarian reserve . CLINICAL TRIALS IDENTIFIER NTR1457 This single-centre , r and omized , parallel group , comparative study aim ed to identify potential benefits of mid-follicular recombinant human LH ( r-HLH ) supplementation in women aged 35 - 39 years undergoing ovarian stimulation for intracytoplasmic sperm injection ( ICSI ) . The main endpoint was the number of metaphase II oocytes retrieved . After pituitary suppression with a gonadotrophin-releasing hormone agonist , ovarian stimulation was initiated with recombinant human FSH ( r-HFSH ; 300 - 450 IU/day ) . On stimulation day 6 , patients were r and omized to receive r-HFSH alone or r-HFSH + r-HLH ( r-HLH 150 IU/day ) for the remainder of the stimulation period . Final follicular maturation was triggered with 250 mug of recombinant human chorionic gonadotrophin . After assessing oocyte nuclear maturity , oocyte were fertilized by ICSI and afterwards embryo quality was analyzed . Of the 131 women enrolled , 68 were allocated to r-HFSH alone and 63 to r-HFSH + r-HLH . No significant differences were observed in markers of either oocyte or embryo quality or quantity . However , higher rates of implantation and live birth per started cycle were observed with r-HLH supplementation than with r-HFSH alone . Although additional large studies are required to further investigate these findings , r-HLH supplementation for women aged 35 - 39 years undergoing ICSI is recommended as it may have a beneficial action on implantation BACKGROUND In approximately 12 - 14 % of young normogonadotrophic women treated with a depot GnRH agonist long protocol , the initial ovarian response to recombinant human FSH ( rFSH ) can be suboptimal . We have tested the hypothesis that these women may benefit from recombinant human LH ( rLH ) supplementation in a multicentre , prospect i ve , r and omized trial compared with patients treated with an rFSH step-up protocol . METHODS A total of 260 young normogonadotrophic women undergoing controlled ovarian stimulation with a GnRH agonist long protocol for IVF/ICSI were enrolled . The starting dose of rFSH was 225 IU . One hundred and thirty patients with serum estradiol levels < 180 pg/ml and with at least six follicles with a mean diameter > 5 mm but none > 10 mm on both day 5 and day 8 of stimulation were r and omly allocated to two groups . From the eighth day of stimulation , women in group A ( n=65 ) received 150 IU of rLH in addition to rFSH , while those in group B ( n=65 ) had an increase of 150 IU in the daily dose of rFSH ( step-up protocol ) . One hundred and thirty normally responding women continued monotherapy with rFSH and served as a further control population ( group C ) . RESULTS The mean number of cumulus-oocyte complexes retrieved in group A ( 9.0+/-4.3 ) was significantly higher ( P<0.01 ) compared with group B ( rFSH 6.1+/-2.6 ) but significantly lower compared with group C ( 10.49+/-3.7 , P<0.05 ) . Implantation and pregnancy rates were significantly lower ( P<0.05 ) in the rFSH step-up group ( 10.5 and 29.3 % respectively ) when compared with normal responders ( 18.1 and 47.3 % respectively ) . CONCLUSIONS rLH supplementation is more effective than increasing the dose of rFSH in terms of ovarian outcome in patients with an initial inadequate ovarian response to rFSH alone BACKGROUND The effect of recombinant human LH ( r-hLH ; lutropin alfa ) in women undergoing controlled ovarian stimulation with recombinant human FSH ( r-hFSH ) prior to IVF was investigated . METHODS After down-regulation with the GnRH agonist , buserelin , 114 normo-ovulatory women ( aged 18 - 37 years ) received r-hFSH alone until the lead follicle reached a diameter of 14 mm . Patients were then r and omized in a double-blind fashion to receive r-hFSH in addition to r-hLH , 75 IU s.c . , or placebo daily for a maximum of 10 days prior to oocyte retrieval and IVF . The primary end-point was the number of metaphase II oocytes . RESULTS There were no significant differences between treatment groups for the primary end-point . Serum estradiol concentrations on the day of HCG administration were significantly higher in the group receiving r-hLH plus r-hFSH than in the group receiving r-hFSH alone ( P = 0.0001 ) , but there were no significant differences between the groups in dose and duration of r-hFSH treatment required , oocyte maturation , fertilization rate , pregnancy rate and live birth rate . CONCLUSION In this patient population , the addition of r-hLH during the late follicular phase of a long GnRH agonist and r-hFSH stimulation cycle provides no further benefit in terms of oocyte maturation or other end-points OBJECTIVE To prospect ively assess the effect of using a combination of recombinant follicle-stimulating hormone ( rFSH ) and recombinant luteinizing hormone ( rLH ) on ovarian stimulation parameters and treatment outcome among poor-responder patients . DESIGN Prospect i ve r and omized trial . SETTING University-associated private medical center . PATIENT(S ) Eighty-four patients who had a basal FSH level of > or=10 mIU/mL , who were > or=40 years of age , and who were undergoing their first IVF cycle participated in this controlled trial . INTERVENTION(S ) Patients were r and omly allocated into two study groups : group A , in which ovarian stimulation included GnRH analogue and rFSH and rLH , and group B , in which patients received GnRH analogue and rFSH without further LH addition . MAIN OUTCOME MEASURE(S ) Primary outcome measures included the ongoing pregnancy rate per retrieval and implantation rate per embryo transferred . The number of days of gonadotropin treatment , E(2 ) level on rHCG administration day , number of developed follicles , number of retrieved oocytes , number of normally fertilized zygotes ( at the two-pronuclear [ 2PN ] stage ) , cumulative embryo score , and number of transferred embryos were also evaluated . RESULT ( S ) The overall pregnancy rate was 22.61 % ( 19 pregnancies among 84 couples ) . The pregnancy wastage rate was 30.00 % in group A and 22.22 % in group B. There were no differences in either primary or secondary end points . CONCLUSION ( S ) The results of this prospect i ve and r and omized trial show that the addition of rLH at a given time of follicular development produces no further benefit in the patient population of our study . A reduced ovarian response can not be overcome by changes in the stimulation protocol BACKGROUND When administered in the late follicular phase to prevent an LH surge , GnRH antagonists induce a sharp decrease in serum LH levels that may be detrimental for assisted reproductive technology cycle outcome . Therefore , a prospect i ve study was design ed to assess the effects of recombinant human (r)LH supplementation during GnRH antagonist ( cetrorelix ) administration . METHODS The protocol consisted of cycle programming with oral contraceptive pill , ovarian stimulation with rFSH and flexible administration of a single dose of cetrorelix ( 3 mg ) . A total of 218 patients from three IVF centres were r and omized ( by sealed envelopes or according to woman 's birth date ) to receive ( n = 114 ) or not ( n = 104 ) a daily injection of rLH 75 IU from GnRH antagonist initiation to hCG injection . RESULTS The only significant difference was a higher serum peak E2 level in patients treated with rLH ( 1476 + /- 787 versus 1012 + /- 659 pg/ml , P < 0.001 ) whereas the numbers of oocytes and embryos as well as the delivery rate ( 25.2 versus 24 % ) and the implantation rate per embryo ( 19.1 versus 17.4 % ) were similar in both groups . CONCLUSIONS These results show that in an unselected group of patients , there is no evident benefit to supplement GnRH antagonist-treated cycles with rLH OBJECTIVE To analyze the impact of LH administration on cycle outcome in ovarian stimulation with GnRH antagonists . DESIGN R and omized , open-label , controlled trial performed in two age subgroups . Recombinant ( r ) FSH versus rFSH + rLH administration was compared . SETTING University-affiliated private infertility clinic . PATIENT(S ) Up to 35 years old ( n = 380 ) and aged 36 to 39 years ( n = 340 ) , undergoing their first or second IVF cycle . INTERVENTION(S ) Recombinant LH administration since stimulation day 1 . MAIN OUTCOME MEASURE(S ) Implantation rate , ongoing pregnancy rate . RESULT ( S ) In the young population , implantation rates were similar : 27.8 % versus 28.6 % , odds ratio ( OR ) 1.03 ( 95 % confidence interval [ CI ] 0.73 - 1.47 ) , as was the ongoing pregnancy rate per started cycle : 37.4 % versus 37.4 % , OR 1.0 ( 95 % CI 0.66 - 1.52 ) . In older patients , the implantation rate was significantly higher in the rFSH + rLH group : 26.7 % versus 18.6 % , OR 1.56 ( 95 % CI 1.04 - 2.33 ) . Ongoing pregnancy rates per started cycle were 33.5 % versus 25.3 % , OR 1.49 ( 95 % CI 0.93 - 2.38 ) . CONCLUSION ( S ) Recombinant LH administration significantly increased the implantation rate in patients aged 36 to 39 years . A clinical ly relevant better ongoing pregnancy rate per started cycle was observed , although the difference was not statistically significant . Patients younger than 36 years do not obtain any benefit from rLH administration BACKGROUND The purpose of this multicentre , multinational trial was to study whether rLH supplementation to recombinant FSH ( rFSH ) during the late follicular phase increased pregnancy rates . METHODS After down-regulation with nafarelin , 526 women were r and omized on Day 1 of stimulation to use either rFSH ( Gonal-F ) alone ( n = 261 ) or to continue after Day 6 of stimulation with both rFSH ( Gonal-F ) and rLH ( Luveris ) ( n = 265 ) from Day 6 . The starting dose of rFSH was 150 - 225 IU/day according to age below or above 35 years . RESULTS Ongoing pregnancy rate at week 10 - 12 was 28.7 % after rFSH alone and 27.2 % after rFSH + rLH . This showed no evidence of a difference . Administration of rLH significantly ( P < 0.001 ) increased serum LH . Ongoing pregnancy rates in patients with low LH levels ( <33 percentile ) on Days 1 and 6 of stimulation showed no difference between the group treated with rFSH only ( 23.9 % low Day 1 LH ; 22.1 % low Day 6 LH ) versus rFSH + rLH ( 25.0 % low Day 1 LH ; 28.9 % low Day 6 LH ) . CONCLUSIONS Supplementing rFSH with daily doses of 75 - 150 IU of rLH during the second half of the follicular phase showed no evidence of increasing the ongoing pregnancy rates in the general population . ( Clinical Trials.gov , trial number : KF02 - 035/03 ) Aim . The aim of our study is to evaluate the effect of recombinant-human LH supplementation on ovarian response and pregnancy outcome , during ovarian stimulation , in down-regulated women with baseline low serum LH levels undergoing assisted reproductive technology . Study design . A prospect i ve r and omized study performed with 80 women , with serum LH levels < 0.5 IU/l on cycle Day 6 of stimulation . Group-A ( 40 ) : 14-days after down-regulation with leuprorelin , ovarian stimulation was initiated only with r-FSH 225 IU . Group-B ( 40 ) : at the same time stimulation was initiated with rFSH 225 IU associated with rLH 75 UI on cycle Day 6 of stimulation . Results . Serum-E2 levels on the hCG-day administration were significantly reduced in the Group-A. FF-VEGF levels were higher in Group-A. We did not find significant differences in the number of retrieved oocytes . The quality of oocytes proved to be higher and more significant from a statistical point of view in Group-B. The number of embryos obtained and transferred , the pregnancy rate lower in Group-A. Conclusions . In our study , it was shown that LH supplementation seems to have a beneficial effect on the maturity and fertilizability of oocyte . Lower FF VEGF levels , found in Group B , could be an indication of a lower apoptosis rate in human cumulus cells after administration of LH . We can affirm that LH-supplementation is beneficial in patients who show a significant serum LH suppression during the receptorial An open label , r and omized , multi-centre study was performed to compare cetrorelix and leuprolide acetate for prevention of premature LH surge and to assess whether patients treated with cetrorelix benefit from addition of recombinant human (r-h)LH . Normo-ovulatory women ( n = 74 ) undergoing ovarian stimulation prior to intracytoplasmic sperm injection were treated with leuprolide acetate ( n = 25 ) before ovarian stimulation with recombinant human FSH ( r-hFSH ) or with cetrorelix 3 mg on stimulation day 7 ( with ( n = 25 ) or without ( n = 24 ) r-hLH 150 IU on days 7 - 10 ) . The main outcome measures were the number of metaphase II ( MII ) oocytes retrieved ; secondary efficacy end-points ; adverse events ( AE ) and other safety measures . There were no significant differences between groups for MII oocytes retrieved , duration of stimulation , total r-hFSH dose and pregnancy rates . The group treated with cetrorelix alone had a significantly lower concentration of oestradiol per follicle compared with the other groups . The majority of AE were mild to moderate in severity . Cetrorelix and leuprolide acetate appear to have comparable efficacy and safety , although cetrorelix has the advantage of typically requiring only one injection OBJECTIVE To investigate the role of exogenous LH in controlled ovarian hyperstimulation for assisted reproductive technologies . DESIGN Prospect i ve r and omized study . SETTING SISMER fertility unit . PATIENT(S ) Women showing a hyporesponsiveness to FSH under GnRH agonist down-regulation were r and omized into three groups : group A ( n = 54 ) received an increased dosage of FSH ; group B ( n = 54 ) was administered recombinant LH in addition to the increased dose of FSH ; group C ( n = 22 ) was given additional FSH and LH using hMG as a combined drug . Fifty-four age-matched women with no need to increase the FSH dose were included as a control group ( D ) . INTERVENTION(S ) None . MAIN OUTCOME MEASURE(S ) Implantation and live birth rate per started cycles . RESULT ( S ) In group B , the pregnancy and implantation rates were statistically higher when compared with groups A and C and did not differ from the control group for normal response . The live birth rate was similar in groups B and D but was half as high in groups A and C. CONCLUSION ( S ) Hyporesponsiveness to FSH could be related to iatrogenic LH deficiency that , in turn , could affect oocyte competence . Addition of a small amount of recombinant LH is able to rescue oocyte competence to produce viable embryos The aim of this study was to evaluate the use of recombinant luteinizing hormone ( rLH ) supplementation in an unselected group of IVF patients undergoing follicular stimulation with recombinant follicle stimulating hormone ( rFSH ) after pituitary down-regulation . Group A comprised 122 cycles administered rFSH and rLH while group B included 331 cycles using rFSH only during the same period of treatment . There was no significant difference in any of the endocrine , embryological and outcome parameters measured . The implantation rate of 14.2 % for group A compared with 9.8 % for group B showed a positive trend ( P = 0.055 ) , but for patients in whom LH concentration was < 1.0 IU/l at down-regulation or required excessive FSH stimulation , there was an increased incidence of implantation if rLH was supplemented . It was concluded that the addition of exogenous rLH to an unselected group of ' down-regulated ' patients stimulated with rFSH appears to offer little benefit , but in the event of profound LH down-regulation or requirement for excessive exogenous FSH ( > 2500 IU ) , the rate of implantation might be improved Circulating endogenous concentrations of LH are reduced in women undergoing down-regulation with gonadotrophin-releasing hormone agonists ( GnRHa ) and ovarian stimulation with recombinant human FSH ( r-hFSH ) . The effect of recombinant human LH ( r-hLH ) supplementation on ovarian response and pregnancy outcome was evaluated in a prospect i ve r and omized study ( sealed envelopes ) including 231 cycles . Normogonadotrophic women were stimulated with either r-hFSH or a combination of r-hFSH and r-hLH in a ratio of 2:1 . LH supplementation was started from day 8 of the cycle . Blood sample s for oestradiol , LH and and rostendione were prospect ively collected on days 1 , 8 and on the day of aspiration and analysed retrospectively . Overall , the two groups did not differ with respect to pregnancy rate . In contrast , women aged > or = 35 years responded to exogenous LH supplementation with significantly increased implantation rates and significantly reduced total FSH consumption as compared with the non-supplemented group . In addition , the implantation rate for a subgroup of patients with the highest endogenous LH concentrations ( i.e. > or = 1.99 IU/l ) on day 8 was significantly increased by LH supplementation . Exogenous LH supplementation from day 8 has no detrimental effect on ovarian response and pregnancy outcome . On the contrary supplementation with r-hLH seems to benefit treatment outcome for women above 35 years of age and for the subgroup of women exhibiting LH concentrations above 1.99 IU/l on stimulation day 8 OBJECTIVE To determine in vivo whether LH supplementation during the late follicular phase induces increased production of ovarian follicle adiponectin in humans . DESIGN R and omized , double-blind , placebo-controlled study . SETTING Academic tertiary care medical center . PATIENT(S ) Twenty infertile , healthy women ( aged 18 - 39 years ) undergoing IVF . INTERVENTION(S ) Administration of recombinant FSH after down-regulation and equal r and omization of subjects to receive recombinant LH 75 IU/day or placebo when two or more follicles reached a mean diameter of 14 mm . MAIN OUTCOME MEASURE(S ) Follicular fluid ( FF ) adiponectin levels were measured . RESULT ( S ) Adiponectin FF levels were significantly higher in the recombinant LH group compared with the placebo group , and these differences were unaltered after correction to estrogen ( E ) levels and number of follicles in each cycle . CONCLUSION ( S ) This is the first demonstration of in vivo induction of adiponectin by gonadotropins in the human ovary . The addition of recombinant LH during the late follicular phase may enhance follicular insulin sensitivity , result ing in decreased and rogen levels through a cascade mediated by increased production of adiponectin OBJECTIVE The objective was to verify the outcome of intracytoplasmic sperm injection ( ICSI ) with ovulation induction performed with GnRH antagonists , comparing the use of recombinant follicle-stimulating hormone ( r-FSH ) alone and in combination with recombinant luteinizing hormone ( r-LH ) in a prospect i ve and r and omized trial . STUDY DESIGN Forty male-factor infertile normo-ovulatory patients undergoing ovarian stimulation for ICSI took part in the study . After initiating ovarian stimulation with only r-FSH , all patients were treated with GnRH antagonist ( cetrorelix ) . When beginning cetrorelix administration , the patients were r and omized into two groups : in group I , 20 patients continued to receive r-FSH alone and in group II , 20 patients received combined r-FSH and r-LH . The number of metaphase II oocytes , estradiol concentration at the time of hCG administration , fertilization rate , grade 1 embryo rate , pregnancy rate per cycle , and implantation rate were measured . Results are expressed as mean+/-S.D. RESULTS In group I , the women 's age was 32.3+/-2.30 years , and FSH concentration was 7.8+/-1.7 IU/ml . In group II , the women 's age was 32.2+/-2.46 years and FSH concentration was 7.5+/-1.7 IU/ml . The number of oocytes retrieved was 9.6+/-2.9 and the number of metaphase II oocytes was 6.7+/-2.2 in group I. In group II the number of retrieved oocytes were 9.9+/-2.6 and the number of metaphase II oocytes 6.9+/-2.1 ( p>0.05 ) . Estradiol concentration at the time of hCG was 4.6+/-1.8 nm/l in group I and 6.7+/-2.0 nm/l in group II ( p<0.01 ) . Fertilization rate was 73.0 % in group I versus 78.2 % in group II . In group I , we obtained 53.9 % of grade 1 embryos versus 54.4 % in group II ( p>0.05 ) . Pregnancy and implantation rates in group I were 30.0 and 16.7 % , respectively and in group II 35.0 and 20.4 % , respectively ( p>0.05 ) . CONCLUSIONS The use of recombinant LH in addition to recombinant FSH may prevent a decrease in estradiol after GnRH antagonist administration , but does not influence positively the outcome of oocyte number , maturation , embryo quality , fertilization rate , pregnancy rate per cycle , and implantation rate BACKGROUND Suppression of endogenous LH production by mid-follicular phase GnRH-antagonist administration in controlled ovarian hyperstimulation protocol using recombinant ( rec ) FSH preparations void of LH activity may potentially affect ovarian response and the outcome of IVF treatment . The present study prospect ively assessed the effect of using a combination of recFSH and recLH on ovarian stimulation parameters and treatment outcome in a fixed GnRH-antagonist multiple dose protocol . METHODS 127 infertile patients with an indication for IVF or ICSI were recruited and r and omized ( using sealed envelopes ) to receive a starting dose of either 150 IU recFSH ( follitropin alpha ) or 150 IU recFSH plus 75 IU recLH ( lutropin alpha ) for ovarian hyperstimulation . GnRH-antagonist ( Cetrorelix ) 0.25 mg was administered daily from stimulation day 6 onwards up to and including the day of the administration of recombinant HCG ( chorion gonadotropin alpha ) . Gonadotropin dose adjustments were allowed from stimulation day 6 onwards , HCG was administered as soon as three follicles > or = 18 mm were present . The primary outcome parameter was treatment duration until administration of HCG . RESULTS Exogenous LH did not shorten the time necessary to reach ovulation induction criteria . Serum estradiol ( E(2 ) ) and LH levels were significantly higher on the day of HCG administration in the recLH-supplemented group ( 1924.7 + /- 1256.4 vs 1488.3 + /- 824.0 pg/ml , P < 0.03 ) , and 2.1 + /- 1.4 vs 1.4 + /- 1.5 IU/l , P < 0.01 , respectively ) . CONCLUSIONS Except for higher E(2 ) and LH levels on the day of HCG administration , no positive trend in favour of additional LH was found as defined by treatment outcome parameters OBJECTIVE To assess the clinical effects of recombinant luteinizing hormone ( LH ) or low-dose recombinant human chorionic gonadotropin ( hCG ) supplementation administered in the midfollicular phase in microdose gonadotropin-releasing hormone analogue ( GnRH-a ) flare-up cycles . DESIGN Prospect i ve r and omized study . SETTING Private infertility clinic . PATIENT(S ) A total of 170 women enrolled , with 145 women eligible for r and omization . INTERVENTION(S ) After r and omization , 51 patients ( group A ) received only 600 IU of recombinant follicle-stimulating hormone ( FSH ) as the control group , 46 patients ( group B ) received 600 IU of recombinant FSH plus daily supplementation with 75 IU of recombinant luteinizing hormone , and 48 patients ( group C ) received 600 IU of recombinant FSH plus daily supplementation with 75 IU of recombinant hCG . MAIN OUTCOME MEASURE(S ) Peak estradiol ( E(2 ) ) levels , days of stimulation with recombinant FSH , total recombinant FSH dosage , metaphase II oocytes retrieved , pregnancy rate ( positive hCG levels ) , clinical pregnancy rate ( positive fetal cardiac activity ) , and cancellation rates of stimulation and embryo transfer . RESULT ( S ) The pregnancy rates were 35.1 % , 27.6 % and 31.2 % for groups A , B , and C , respectively . Clinical pregnancy rates were 27.1 % , 27.5 , and 21.8 % for groups A , B , and C , respectively . There were no statistically significant differences in the age , peak serum E(2 ) concentration , total recombinant FSH dosage , days of stimulation with recombinant FSH , total number of metaphase II oocytes retrieved , number of embryos transferred , pregnancy rates , clinical pregnancy rates , or cancellation rates of stimulation and embryo transfer among the three groups . CONCLUSION ( S ) Additional exogenous LH activity in the form of either recombinant luteinizing hormone or low-dose recombinant hCG is unnecessary in microdose cycles to increase pregnancy rates OBJECTIVE To study the effect of early follicular phase recombinant LH supplementation on stimulation outcome among women undergoing IVF using the GnRHa long protocol and recombinant FSH . DESIGN R and omized , controlled trial . SETTING Private IVF unit . PATIENT(S ) Women under the age of 40 with normal ovarian function undergoing their first or second IVF cycle . INTERVENTION(S ) All stimulations followed the st and ard luteal long GnRHa down-regulation protocol . At suppression , patients in the experimental group received 75 IU of rLH daily for 4 days , and recombinant FSH at a fixed starting dose of 150 IU for the first 5 days was started a day later , on day 2 of rLH . In the control group , patients started rFSH at a fixed dose of 150 IU for the first 5 days at suppression . MAIN OUTCOME MEASURE(S ) Baseline , stimulation , embryology parameters , and treatment outcome were compared . Of primary interest , recombinant FSH need during stimulation was assessed . RESULT ( S ) Stimulation , embryology parameters , and treatment outcome were comparable . The amount of gonadotropins used and medication expense were similar in the two groups . CONCLUSION ( S ) Early follicular phase recombinant LH supplementation at a daily dose of 75 IU does not improve response to stimulation among normal responder women undergoing IVF In contrast to gonadotropin-releasing hormone ( GnRH ) agonists , GnRH antagonists do not show any stimulatory effect on the pituitary but their clinical usage was precluded by severe side effects and high dose requirements . We report here on a 7-day treatment using the potent GnRH antagonist Cetrorelix ( [ Ac-D-Nal(2)1 , D-Phe(4Cl)2 , D-Pal(3)3 , D-Cit6 , D-Ala10]GnRH ) on five women 23 - 33 years old . All women were ovulatory and were studied during three consecutive cycles : a control cycle , a treatment cycle and a post-treatment control cycle . Throughout the control cycles blood sample s were obtained daily during cycle days 8 - 18 and on days 21 and 23 during the remainder of the control cycles . On the eighth day of the treatment cycle women were hospitalized at 07.00 h for 26 h. Repeated blood sample s were drawn at 15-min intervals during the entire period . Subjects received 3 mg of Cetrorelix sc for the first time at 09.00 h on the eighth day of the cycle and daily at 08.00 h for the following 6 days . Blood sample s were obtained daily over a period of 25 days and every third day throughout the remainder of the treatment cycle . Twenty-four hours after the first application of Cetrorelix , luteinizing hormone ( LH ) and estradiol were in the subnormal range and remained subnormal until the end of medication . The suppressive effect of Cetrorelix compared to pretreatment values lasted at least 6 days for LH and FSH and 11 days after the last Cetrorelix injection for estradiol . ( ABSTRACT TRUNCATED AT 250 WORDS |
1,242 | 22,417,281 | We could not explain the considerable differences in hospitalization and quality of life across the studies .
Chronic care management significantly reduces mortality .
Positive effects on hospitalization and quality of life were shown , however , with substantial heterogeneity in effectiveness .
This heterogeneity is not explained by study quality , length of follow-up , or the number of chronic care model components . | OBJECTIVE To support decision making on how to best re design chronic care by study ing the heterogeneity in effectiveness across chronic care management evaluations for heart failure . | BACKGROUND Heart failure , a condition predominantly affecting the elderly , represents an ever-increasing clinical and financial burden for the NHS . Cardiac rehabilitation , a service that incorporates patient education , exercise training and lifestyle modification , requires further evaluation in heart failure management . AIM The aim of this study was to determine whether a cardiac rehabilitation programme improved on the outcomes of an outpatient heart failure clinic ( st and ard care ) for patients , over 60 years of age , with chronic heart failure . METHODS Two hundred patients ( 60 - 89 years , 66 % male ) with New York Heart Association ( NYHA ) II or III heart failure confirmed by echocardiography were r and omised . Both st and ard care and experimental groups attended clinic with a cardiologist and specialist nurse every 8 weeks . Interventions included exercise prescription , education , dietetics , occupational therapy and psychosocial counselling . The main outcome measures were functional status ( NYHA , 6-min walk ) , health-related quality of life ( MLHF and EuroQol ) and hospital admissions . RESULTS There were significant improvements in MLHF and EuroQol scores , NYHA classification and 6-min walking distance ( meters ) at 24 weeks between the groups ( p<0.001 ) . The experimental group had fewer admissions ( 11 vs. 33 , p<0.01 ) and spent fewer days in hospital ( 41 vs. 187 , p<0.001 ) . CONCLUSIONS Cardiac rehabilitation , already widely established in the UK , offers an effective model of care for older patients with heart failure IN THE EARLY 1890S , DR WILLIAM HALSTED DEVELOPED radical mastectomy for breast cancer . Surgeons performed the Halsted procedure for more than 80 years even though there was little systematic evidence for its success . Then a new breed of scholars subjected the procedure to formal methods of evaluation unknown to Halsted . The methods —r and omized controlled trials ( RCTs ) principal among them — led to a surprise : radical mastectomy had no advantage over simpler forms of treatment . This is but 1 example of the hard-won victory of evidence over belief in medicine . The pioneers of the formal evaluation of medical practice s raised questions that traditional practitioners did not welcome . But in time , formal evaluation prevailed . The pioneers developed a hierarchy of evidentiary rigor relating the design of a study to the confidence that could be placed in the findings , from the lowly , nearly valueless anecdote to the royalty of evidence , the RCT . Concurrently , a similar story of hard-won learning unfolded in the so-called quality movement . Scholars illuminated the scale and types of defects in the processes of care and the outcomes , including high rates of unscientific care , inappropriate care , geographic variations in practice , latent disagreements among specialists , and oftenunrecognized medical injury to patients . Like the pioneers of evidence -based medicine , students of medical quality were at first largely ignored , but no longer . In 1999 and 2001 , the Institute of Medicine published 2 l and mark reports on the evidence for quality failures and called urgently for re design of care systems to achieve improvements . The story could end here happily with 2 great streams of endeavor merging into a framework for conjoint action : improving clinical evidence and improving the process of care . Instead , the 2 endeavors are often in unhappy tension . Neither disputes that progress toward health care ’s main goal , the relief of illness and pain , requires research of many kinds : basic , clinical , systems , epidemiologic . The disagreement centers on epistemology — ways to get at “ truth ” and how those ways should vary depending on the knowledge sought . Individuals most involved in day-to-day improvement work fear that if “ evidence ” is too narrowly defined and the approach to gathering evidence too severely constrained , progress may be the victim . For example , the RCT is a powerful , perhaps unequaled , research design to explore the efficacy of conceptually neat components of clinical practice —tests , drugs , and procedures . For other crucially important learning purpose s , however , it serves less well . Recent controversies about the evaluation of rapid response teams provide a case in point . These controversies show the importance of adjusting research methods to fit research questions . Although only 10 % to 15 % of in patients resuscitated outside intensive care units survive to hospital discharge , early warning signs are present in a large percentage of patients who ultimately experience cardiac arrest . Rapid response team systems bring expert clinicians to the bedsides of deteriorating patients before arrest occurs . In the mid 1990s , based largely on reports from Australian investigators , the Institute for Healthcare Improvement and others began introducing the concept to willing hospitals . Local experience strongly suggested that these systems often , although not always , were associated with improved outcomes , including reduced anxiety among nursing staff ; increased interdisciplinary teamwork ; decreased cardiac arrests outside of intensive care units ; and , in some cases , declines in mortality . The evidence base took a turn in June 2005 with the publication of the Medical Early Response Intervention and Therapy ( MERIT ) Study , a cluster r and omized prospect i ve trial that cl aim ed to find no beneficial effect of these teams on several primary outcomes . Controversy has continued since then regarding the scientific evidence for rapid response systems . In fact , the MERIT trial was not negative ; it was inconclusive . The study team encountered an array of serious problems in execution , common in social science . For example , although the study ’s power calculation assumed a baseline rate of 30 events per 1000 admissions , the actual rate proved to be fewer than 7 events per 1000 admissions ; thus , the study was ef fect ively underpowered by 500 % . Crosscontamination abounded ; some control hospitals implemented rapid response protocol s , and several study 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 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 Despite efforts to improve the discharge planning process and subsequent outcomes , existing mechanisms fail to accurately identify elders ' needs for follow-up care . Studies report rehospitalization rates ranging from 12 to 50 % . The two aims of this study were to ( 1 ) examine the difference in outcomes for elders hospitalized with heart failure and caregivers who participated in a professional-patient partnership model of discharge planning compared to those who received the usual discharge planning and ( 2 ) examine differences in costs associated with hospital readmission and use of the emergency room following hospital discharge . A before- and -after nonequivalent control group design was used for this study . Data were collected from the control and the intervention cohorts before discharge and at 2 weeks and 2 months postdischarge . One hundred and fifty-eight patient-caregiver dyads completed both the predischarge and 2-weeks postdischarge interviews ; 140 also completed a 2-month follow up . The average age of elders was 73.7 years ; the average age of the caregivers was 58.5 years . The findings indicated that elders in the intervention cohort felt more prepared to manage care , reported more continuity of information about care management and services , felt they were in better health , and when readmitted spent fewer days in the hospital than the control cohort . Caregivers in the intervention cohort also reported receiving more information about care management and having a more positive reaction to caregiving 2 weeks postdischarge than the control cohort 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 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 Background —The dissemination of clinical practice guidelines often has not been accompanied by desired improvements in guideline adherence . This study evaluated interventions for implementing a new practice guideline advocating the use of & bgr;-blockers for heart failure patients . Methods and Results —This was a r and omized controlled trial involving heart failure patients ( n=169 ) with an ejection fraction ≤45 % and no contraindications to & bgr;-blockers . Patients ’ primary providers were r and omized in a stratified design to 1 of 3 interventions : ( 1 ) control : provider education ; ( 2 ) provider and patient notification : computerized provider reminders and patient letters advocating & bgr;-blockers ; and ( 3 ) nurse facilitator : supervised nurse to initiate and titrate & bgr;-blockers . The primary outcome , the proportion of patients who were initiated or uptitrated and maintained on & bgr;-blockers , analyzed by intention to treat , was achieved in 67 % ( 36 of 54 ) of patients in the nurse facilitator group compared with 16 % ( 10 of 64 ) in the provider/patient notification and 27 % ( 14 of 51 ) in the control groups ( P < 0.001 for the comparisons between the nurse facilitator group and both other groups ) . The proportion of patients on target & bgr;-blocker doses at the study end ( median follow-up , 12 months ) was also highest in the nurse facilitator group ( 43 % ) compared with the control ( 10 % ) and provider/patient notification groups ( 2 % ) ( P < 0.001 ) . There were no differences in adverse events among groups . Conclusions —The use of a nurse facilitator was a successful approach for implementing a & bgr;-blocker guideline in heart failure patients . The use of provider education , clinical reminders , and patient education was of limited value in this setting 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 BACKGROUND The multidisciplinary approach to managing heart failure has been shown to improve outcomes . The role of a clinical pharmacist in treating heart failure has not been evaluated . METHODS One hundred eighty-one patients with heart failure and left ventricular dysfunction ( ejection fraction < 45 ) undergoing evaluation in clinic were r and omized to an intervention or a control group . Patients in the intervention group received clinical pharmacist evaluation , which included medication evaluation , therapeutic recommendations to the attending physician , patient education , and follow-up telemonitoring . The control group received usual care . The primary end point was combined all-cause mortality and heart failure clinical events . All clinical events were adjudicated by a blinded end point committee . RESULTS Baseline characteristics were similar except for slightly higher age in the intervention group . Median follow-up was 6 months . All-cause mortality and heart failure events were significantly lower in the intervention group compared with the control group ( 4 vs 16 ; P= .005 ) . In addition , patients in the intervention group received higher angiotensin-converting enzyme inhibitor doses as reflected by the median fraction of target reached ( 25th and 75th percentiles ) , 1.0 ( 0.5 and 1 ) and 0.5 ( 0.1875 and 1 ) in the intervention and control groups , respectively ( P<.001 ) . The use of other vasodilators in angiotensin-converting enzyme inhibitor-intolerant patients was higher in the intervention group ( 75 % vs 26 % ; P= .02 ) . CONCLUSIONS Outcomes in heart failure can be improved with a clinical pharmacist as a member of the multidisciplinary heart failure team . This observation may be due to higher doses of angiotensin-converting enzyme inhibitors and /or closer follow-up 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 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 The evidence base of what works in chronic care management programs is underdeveloped . To fill the gap , we pooled and reanalyzed data from ten r and omized clinical trials of heart failure care management programs to discern how program delivery methods contribute to patient outcomes . We found that patients enrolled in programs using multi-disciplinary teams and in programs using in-person communication had significantly fewer hospital readmissions and readmission days than routine care patients had . Our study offers policymakers and health plan administrators important guideposts for developing an evidence base on which to build effective policy and programmatic initiatives for chronic care management 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 |
1,243 | 17,280,623 | REVIEW METHODS Data from selected studies were tabulated and the results were qualitatively synthesis ed along with findings from the information design and stakeholder workshop str and s. RESULTS Most people do not value the written information they receive .
They had concerns about the use of complex language and poor visual presentation and in most cases the research showed that the information did not increase knowledge .
The research showed that patients valued written information that was tailored to their individual circumstances and illness , and that contained a balance of harm and benefit information .
Most patients wanted to know about any adverse effects that could arise .
Patients did not want written information to be a substitute for spoken information from their prescriber .
While not everyone wanted written information , those who did wanted sufficient detail to meet their need .
Some health professionals thought that written information for patients should be brief and simple , with concerns about providing side-effect information .
They saw increasing compliance as a prime function , in contrast to patients who saw an informed decision not to take a medicine as an acceptable outcome .
There is a gap between currently provided leaflets and information which patients would value and find more useful . | OBJECTIVES To establish the role and value of written information available to patients about individual medicines from the perspective of patients , carers and professionals .
To determine how effective this information is in improving patients ' knowledge and underst and ing of treatment and health outcomes .
Patients require information to help decision-making about whether to take a medicine or not and ( once taking a medicine ) with ongoing decisions about the management of the medicine and interpreting symptoms .
The challenge is to develop methods of provision flexible enough to allow uptake of varying amounts and types of information , depending on needs at different times in an illness . | Abstract Based on the two legal st and ards of informed consent currently in use , the Medical Practice St and ard and the Reasonable Person St and ard , two disclosures containing information about the risks and benefits of the anticonvulsant , Carbamazepine , were empirically derived . One of these two disclosures was r and omly given to a sample of 39 seizure patients and the parents of pediatric seizure patients prescribed this drug . Subjects were interviewed either immediately after disclosure and at followup , or at followup only . The results provide no evidence for the hypothesized negative effects — anxiety , treatment refusal , reduced compliance and increased side effects — of providing patients with extensive disclosures about prescription drugs Objective : To determine whether the use of verbal descriptors suggested by the European Union ( EU ) such as “ common ” ( 1–10 % frequency ) and “ rare ” ( 0.01–0.1 % ) effectively conveys the level of risk of side effects to people taking a medicine . Design : R and omised controlled study with unconcealed allocation . Participants : 120 adults taking simvastatin or atorvastatin after cardiac surgery or myocardial infa rct ion . Setting : Cardiac rehabilitation clinics at two hospitals in Leeds , UK . Intervention : A written statement about one of the side effects of the medicine ( either constipation or pancreatitis ) . Within each side effect condition half the patients were given the information in verbal form and half in numerical form ( for constipation , “ common ” or 2.5 % ; for pancreatitis , “ rare ” or 0.04 % ) . Main outcome measure : The estimated likelihood of the side effect occurring . Other outcome measures related to the perceived severity of the side effect , its risk to health , and its effect on decisions about whether to take the medicine . Results : The mean likelihood estimate given for the constipation side effect was 34.2 % in the verbal group and 8.1 % in the numerical group ; for pancreatitis it was 18 % in the verbal group and 2.1 % in the numerical group . The verbal descriptors were associated with more negative perceptions of the medicine than their equivalent numerical descriptors . Conclusions : Patients want and need underst and able information about medicines and their risks and benefits . This is essential if they are to become partners in medicine taking . The use of verbal descriptors to improve the level of information about side effect risk leads to overestimation of the level of harm and may lead patients to make inappropriate decisions about whether or not they take the medicine Abstract Objective : To assess whether provision of educational leaflets or questions on contraception improves knowledge of contraception in women taking the combined contraceptive pill . Design : R and omisation of women into three groups according to type of educational leaflet on contraceptive information . These groups were subdivided into two on the basis of questions on contraception asked by the doctor or practice nurse . The women were followed up by postal question naire 3 months later . Setting : 15 general practice s in South and West region . Subjects : 636 women attending check up appointment for repeat prescription of the combined contraceptive pill . Main outcome measures : Knowledge of : factors causing pill failure , subsequent action , emergency contraception , and all the rules ( pill rules ) that apply to the contraceptive pill . Results : 523 women returned completed question naires ( response rate 82 % ) . Knowledge of contraception with no intervention was low with only 10 ( 12 % ) women knowing all the pill rules . Educational intervention had a highly significant effect on knowledge of : factors causing pill failure ( likelihood ratio χ2=22 ) ; subsequent action ( 21 ) ; emergency contraception ( 24 ) ; and all the pill rules ( 22 ) ( P<0.01 in all cases ) . Improvement in knowledge of all the pill rules occurred with provision of the summary leaflet ( 28 % knew all the rules , adjusted odds ratio 4.04 , 95 % confidence interval 1.68 to 9.75 ) , the Family Planning Association 's leaflet ( 27 % , 3.43 , 1.45 to 8.09 ) , and asking questions ( 26 % , 3.03 , 1.30 to 7.00 ) . Asking questions in addition to provision of leaflets improved knowledge of contraception further for the summary leaflet ( 39 % , 6.81 , 2.85 to 16.27 ) but not for the Family Planning Association leaflet ( 21 % , 2.58 , 1.07 to 6.18 ) . Conclusion : Women attending check ups for repeat prescriptions of the contraceptive pill should be provided with educational leaflets on contraception or asked relevant questions to help improve their knowledge of contraception . Asking questions in addition to providing a summary leaflet is time consuming , but results in the most knowledge gained . Key messages It is very important to most women who take the contraceptive pill to avoid pregnancy Poor knowledge of contraception is common in women taking the contraceptive pill and associated with unwanted pregnancy No r and omised trials have been conducted of educational interventions to improve knowledge of contraception Providing leaflets or asking questions both improve knowledge of contraception The largest effect on knowledge of contraception is from asking questions and providing a summary This paper reports the findings of a study of information given to rheumatology patients using non-steroidal anti-inflammatory drugs . One hundred and twenty patients were r and omized to three groups . Group A received an information leaflet , Group B received both a leaflet and a verbal explanation and Group C received only a verbal explanation . Information was gathered on demography , knowledge base , sources of information , satisfaction with the leaflet and further information requirements . Data were collected by question naires which were completed before r and omization and 8 - 12 weeks later . Analysis indicates the potential benefits of giving information to patients although the full implication s of these benefits are not clear and further research is indicated in this important area OBJECTIVES To develop three tools for assessing the quality of written information provided with new prescriptions in community pharmacies and to identify pharmacy , pharmacist , and patient characteristics associated with the dissemination and quality of that information . DESIGN Observational study . Regression techniques were used to analyze the influence of pharmacy , pharmacist , and shopper ( acting as patient ) characteristics on outcome measures . PARTICIPANTS Trained shoppers ( acting as patients ) visited 306 r and omly selected pharmacies in 8 states . Each shopper presented three prescriptions , answered questions according to a st and ard scenario , accepted the information offered , and paid for the prescriptions . MAIN OUTCOME MEASURES Percentage of shoppers receiving any written information ; quality of written information as judged by an expert panel using explicit criteria . RESULTS Shoppers received an information leaflet with 87 % of the 918 prescriptions dispensed . Although most leaflets provided unbiased information , leaflet length and quality of information varied greatly . A majority of leaflets did not include adequate information about contraindications , pre caution s , and how to avoid harm . Shoppers were more likely to receive leaflets in chain pharmacies and pharmacies with more staff . Information quality also was higher in chain pharmacies . Shopper and pharmacist demographic characteristics were unrelated to the level or quality of written information after controlling for other factors . CONCLUSION The provision of patient leaflets is becoming a routine practice in the states studied . However , most leaflets do not meet quality criteria . It is important for pharmacists to become familiar with criteria for evaluating these leaflets and to take necessary action to improve their quality OBJECTIVES The authors determined patients ' report of prescription drug counseling activities after withdrawal of the pilot program to require patient package inserts in 1980 and implementation of Omnibus Budget Reconciliation Act of 1990 counseling requirements in 1993 . METHODS Four cross-sectional national telephone surveys were conducted in the fall of 1982 , 1984 , 1992 , and 1994 . Telephone households were chosen by r and om-digit dialing . Subjects had obtained a new prescription for themselves or for a family member at a retail pharmacy during the previous 4 weeks . Verbal counseling rates at physician offices and pharmacies for five information categories and the distribution of written information at those locations were determined . RESULTS Spontaneous verbal counseling at the physician 's office has increased slightly , with the largest increases focused on the delivery of side effect and pre caution ary information . Slightly larger increases in pharmacy-delivered information regarding directions for use and pre caution s have occurred . Patient question ing has remained at single digit levels at both sites . The percentage of patients receiving any written information has increased from 5 % to 15 % at the physician 's office and from 16 % to 59 % at the pharmacy . CONCLUSIONS The data indicate small increases in verbal counseling but larger increases in the delivery of written information provided at the pharmacy . In light of Healthy People : 2000 goals for patient counseling and legislation encouraging private-sector initiatives , these data should help to refocus attention on the continuing need for effective patient education interventions OBJECTIVE : To investigate whether patients are influenced by the order in which they learn the risks and benefits of a treatment and whether this effect is attenuated by a treatment ’s associated risk and /or benefit . DESIGN : Subjects were r and omized to review 1 of 6 medical treatment information brochures . SETTING : Waiting rooms of primary care physicians at an academic health center . PARTICIPANTS : Six hundred eighty-five subjects , ages 18 to 70 years . INTERVENTION : Subjects review ed 1 of 3 treatments for symptomatic carotid artery disease . The first ( aspirin ) was low-risk/low-benefit , the second ( carotid endarterectomy surgery ) was high-risk/high-benefit , and the third ( extracranial-to-intracranial bypass surgery ) was high-risk but of unknown benefit . Patients were also r and omized to receive information about risk either before or after benefit . Patients were asked to rate the favorability of the treatment on a scale of 0 to 100 and whether they would consent . Finally , subjects rated how their decisions were influenced by the risk and benefit information . MAIN RESULTS : Subjects evaluating aspirin therapy were influenced by the order of the risk/benefit information . Those learning about risks after benefits had a greater drop in their favorability ratings than subjects learning about risks before benefits ( −10.9 vs −5.2 on a 100-point scale ; P=.02 ) and were less likely to consent ( odds ratio , 2.27 ; P=.04 ) . In contrast , subjects evaluating carotid endarterectomy and extracranial-to-intracranial bypass were not influenced by information order . When subjects were influenced by the order of information , they also reported that the treatment ’s risk had less influence on their decision making ( P<.01 ) . CONCLUSIONS : When patients evaluate low-risk medical interventions , they may form less favorable impressions of the treatment and be less likely to consent to the treatment when they learn about the risks after the benefits . Order effects were not observed with high-risk treatments regardless of potential benefits Insulin/sulphonylurea-treated diabetics attending a busy university diabetic clinic were studied to determine whether issuing drug information sheets and /or age influenced underst and ing and behaviour regarding their disease and its treatment , especially with respect to avoiding hypoglycaemia . Patients were each asked 10 basic questions ( each correct answer scoring 1 ) , stratified by age ( 20 were less than or equal to 45 years and 91 greater than 45 years ) . According to a single-blind r and omised protocol , they were issued or not issued with drug information sheets ( providing information to correctly answer all 10 questions ) . After 2 - 3 months , 107 ( 88 aged greater than 45 years ) were retested and asked whether they recalled an information sheet , read it themselves or had it read to them . Whether or not patients received sheets , corresponding mean aggregate scores were very similar in both age groups and there was no correlation with age . Second test scores yielded clinical ly and statistically significant increments in both the sheet and no sheet groups , respective mean aggregate scores increasing from 4.48 to 5.80 and 5.14 to 6.27 ( P less than 0.001 ) . Among patients issued with sheets , 32 who recalled reading them achieved the greatest improvement in mean scores ( 4.53 to 6.16 , P less than 0.001 ) . Active interaction/communication ( participation in first test , recall and reading of information sheet ) had a favourable educational impact irrespective of age , but merely issuing drug information sheets had no benefit 1 . Cardiologists and pharmacists at the University Hospital of Wales collaborated to write 20 individual leaflets incorporating guidelines for a range of drugs used in the treatment of cardiology patients . The Plain English Campaign advised on the intelligibility and presentation of the information . 2 . One hundred and twenty-five patients from the Regional Cardiology Unit , University Hospital of Wales were r and omly allocated to receive usual verbal counselling about their drug treatment with or without an individualised drug information wallet . Two weeks after discharge from hospital patients completed a postal question naire to determine their satisfaction with the information about their drug treatment and their underst and ing of it . Forty-nine question naires were returned from the leaflet group and 52 from the control group . 3 . The provision of written guidelines result ed in significant improvements in patients ' satisfaction with their drug treatment ( chi 2 = 33.3 , P less than 0.001 ) and their underst and ing of it ( P less than 0.001 , Mann-Whitney test ) . Overall , patients who received leaflets were more likely to be aware of the potential side effects of their drugs but less likely to be apprehensive about them . Succinct guidelines concerning drug therapy can be assimilated by cardiology patients and provide them with a permanent record for future reference 1 . Prescription information leaflets ( PILs ) giving information about non-steroidal anti-inflammatory drugs ( NSAIDs ) , beta-adrenoceptor antagonists and inhaled bronchodilators were evaluated in three small Hampshire towns , while a fourth , in which no leaflets were distributed , acted as a control . 2 . Seven hundred and nineteen ( 82 % ) patients prescribed one of these medicines agreed to be interviewed in their homes , 1 to 2 weeks after the medicine had been prescribed . Four hundred and nineteen of them had received leaflets , while 300 received no written information . Two hundred and sixty patients received their leaflets from a pharmacist while 159 were given them by their general practitioner . 3 . Patients who received leaflets were better informed about every item of knowledge tested , except for the name of the medicine . Awareness of the side effects showed the greatest improvement , but there was no evidence that these leaflets produced spurious side effects . 4 . Much improved levels of satisfaction were recorded amongst patients who received leaflets , especially those for NSAIDs ( P less than 0.001 ) and for beta-adrenoceptor antagonists ( P less than 0.01 ) . 5 . Subsequently , three hundred and fifty-eight ( 77 % ) of the patients prescribed either a NSAID or a beta-adrenoceptor antagonist 1 year earlier responded to a postal question naire . The benefits in terms of knowledge and satisfaction were still apparent , although less marked than previously . Of the patients still taking beta-adrenoceptor antagonists 70 % had retained their leaflets over the intervening 12 months . 6 . Ninety-seven per cent of patients read their leaflet regardless of whether it was distributed by a general practitioner or pharmacist . However , those who obtained it from a pharmacist tended to be more knowledgeable and satisfied . 7 . We conclude that patients welcome the idea of receiving PILs . They improve patients ' knowledge of how to take their medicines correctly and their awareness of potential side effects . Importantly , patients who receive leaflets are more satisfied than those who do not . These overall benefits justify the use of leaflets on a routine basis OBJECTIVE We performed a double blind r and omized controlled trial to investigate whether patients taking nonsteroidal antiinflammatory drugs ( NSAID ) knew more about these drugs at followup depending on whether they were r and omized to receiving or not receiving an NSAID information sheet . The patients were unaware they were in a study . METHODS All patients received verbal education on the side effects of NSAID that was st and ardized and always given by the same rheumatologist . Thirty patients r and omly received an NSAID information sheet and 26 patients did not . At next clinic followup , after reading a letter of explanation about the study and signing a consent form , patients completed a question naire asking about their knowledge of NSAID . RESULTS Outcome variables assessed within the question naire included whether NSAID : ( 1 ) can decrease inflammation ; ( 2 ) help with pain ; ( 3 ) cause stomach upset and bleeding in the bowels . None of these variables were statistically significant . The only variable that was statistically significantly different between the groups was their report of whether they had received an information sheet about NSAID ( p<0.00004 ) . A greater proportion of patients who received the NSAID information sheet correctly reported they had received one compared to those who had not received one and who said they had not received one ( 85 % in the former group , 70 % in the latter group ) . The group who received the NSAID information sheet were more apt to say that NSAID can help with their pain ( odds ratio 6.1 , p<0.05 ) . Education level was positively correlated with knowledge ( p<0.04 ) . However , level of education explained only 11 % of the variance in overall knowledge scores ( r=0.34 ) among all patients . CONCLUSION An information sheet may not add educational value over verbal information by a physician in a clinic setting Abstract Objectives : To evaluate two different methods of improving adherence to antidepressant drugs . Design : Factorial r and omised controlled single blind trial of treatment leaflet , drug counselling , both , or treatment as usual . Setting : Primary care in Wessex Participants : 250 patients starting treatment with tricyclic antidepressants . Main outcome measures : Adherence to drug treatment ( by confidential self report and electronic monitor ) ; depressive symptoms and health status . Results : 66 ( 63 % ) patients continued with drugs to 12 weeks in the counselled group compared with 42 ( 39 % ) of those who did not receiving counselling ( odds ratio 2.7 , 95 % confidence interval 1.6 to 4.8 ; number needed to treat=4 ) Treatment leaflets had no significant effect on adherence . No differences in depressive symptoms were found between treatment groups overall , although a significant improvement was found in patients with major depressive disorder receiving drug doses of at least 75 mg ( depression score 4 ( SD 3.7 ) counselling v 5.9 ( SD 5.0 ) no counselling , P=0.038 ) . Conclusions : Counselling about drug treatment significantly improved adherence , but clinical benefit was seen only in patients with major depressive disorder receiving doses ≥75 mg . Further research is required to evaluate the effect of this approach in combination with appropriate targeting of treatment and advice about dosage . Key messages Non-adherence is a serious problem in the treatment of depression by general practitioners In this study a brief psychosocial intervention delivered by a nurse greatly improved adherence Clinical benefit was apparent only in patients with major depressive episodes on higher doses of drugs Counselling should be targeted at patients with symptoms of at least moderate severity and combined with therapeutic drug |
1,244 | 24,504,647 | The diagnostic accuracy of stress radiography including the sensitivity , specificity , and positive and negative predictive values varied considerably depending on the technique and choice of displacement or gapping threshold .
Excellent reliability was reported for the diagnosis of anterior cruciate ligament , posterior cruciate ligament , varus , and valgus knee injuries .
Inconsistencies were found across studies regarding the efficacy of stress radiography compared with other diagnostic modalities .
Conclusions Based on the multitude of stress techniques reported , varying levels of diagnostic accuracy , and inconsistencies regarding comparative efficacy of stress radiography to other diagnostic modalities , we are not able to make specific recommendations with regard to the best stress radiography technique for the diagnosis of knee ligament injuries . | Background Stress radiography is a widely used diagnostic tool to assess injury to the anterior and posterior cruciate ligaments and the medial and lateral structures of the knee .
However , to date , numerous techniques have been reported in the literature with no clear consensus as to which methodology is best for assessing ligament stability .
Questions / purpose sThe purpose of this review was to identify which stress radiographic techniques have support in the literature for the diagnosis of acute or chronic knee ligament injuries , to define which technique is most accurate and reliable for diagnosing knee ligament injuries , and to compare the use of stress radiography with other diagnostic tests . | Stress radiography presents the golden st and ard to quantify posterior laxity in posterior cruciate ligament ( PCL ) insufficiency . Several different techniques are currently available , but comparative data are insufficient . Different stress radiographic techniques result in different values for posterior laxity . Comparative controlled clinical study was design ed . Prior to PCL reconstruction 30 patients underwent a series of stress radiographs : Telos device , hamstring contraction , kneeling view , gravity view , and an axial view . Posterior displacement , side-to-side difference ( SSD ) , condyle rotation , required time , and pain were measured . Posterior displacement was : Telos 12.7 ± 3 mm ( SSD 10.6 ± 3.1 mm ) , hamstring contraction 11.2 ± 3.2 mm ( SSD 8.5 ± 3.4 mm ) , kneeling 14.4 ± 3.8 mm ( SSD 10.2 ± 3.5 mm ) , gravity view 10.5 ± 2.8 mm ( SSD 9.1 ± 2.4 mm ) , and axial view 19.4 ± 6.9 mm ( SSD 8.5 ± 4.1 mm ) . In comparison to Telos the hamstring contraction , gravity , and the axial view underestimated the SSD by approximately 2 mm . Telos and kneeling caused significantly more pain than all other techniques ( P < 0.001 ) . The axial view was fastest ( 115 s , P < 0.001 ) and Telos longest ( 305 s , P < 0.001 ) , respectively . Telos indicated the lowest rotational error with a significant difference between kneeling and gravity ( P < 0.003 ) . In contrast to Telos as the golden st and ard , hamstring contraction , gravity , and axial view underestimated the SSD . Kneeling and Telos are comparable with respect to SSD and pain . Although kneeling indicates a greater rotational error than Telos , it seems to be a reliable alternative for quantifying posterior tibial displacement in a more simple and fast way INTRODUCTION In patients with anterior cruciate ligament ( ACL ) tears , anterior laxity can be measured using stress radiographs or more recently introduced electronic measurement devices . HYPOTHESIS The GNRB ( ® ) arthrometer offers a radiation-free method of measuring anterior knee laxity whose diagnostic value is identical to that of Telos ( ® ) or Lerat stress radiographs . PATIENTS AND METHODS One hundred and fifty-seven patients ( 40 years [ 18 - 69 ] ) scheduled for knee arthroscopy were evaluated using the GNRB ( ® ) and two series of stress radiographs of both knees , one obtained using a 250-N Telos ( ® ) device and the other using the technique described by Lerat ( posterior translation of the femur/tibia under a 9-kg loading device ) . Arthroscopic evaluation of the ACL served as the reference st and ard for assessing the diagnostic performance of the radiological and instrumental laxity measurements . RESULTS Under arthroscopic examination , the ACL was normal in 50.3 % ; " healed to roof of the notch " ( partial tear ) in 9.6 % , " posterolateral bundle preserved " ( partial tear ) in 7.0 % , " healed to the posterior cruciate ligament " ( PCL ) in 17.8 % , and " empty notch " ( complete tear ) in 15.3 % . In partial ACL tears , no significant differences in anterior laxity were found across the three measurement techniques . Telos ( ® ) and GNRB ( ® ) laxities were greater in the complete-tear group than in the normal-ACL , partial-tear , and healed-to-PCL groups . With the Lerat technique , the only significant differences were between the complete-tear group and the normal-ACL and partial-tear groups . Telos ( ® ) and GNRB ( ® ) showed similar diagnostic performance ( sensitivity>62 % , specificity>75 % ) , whereas the Lerat technique lacked sensitivity ( sensitivity=43.2 % , specificity=82.7 % ) at 3 mm . DISCUSSION Diagnostic performance was lower in our study than in earlier reports . The GNRB ( ® ) performed as well as Telos ( ® ) . The non-irradiating nature of GNRB ( ® ) assessment s allows repeated measurements for therapeutic or diagnostic purpose s. LEVEL OF EVIDENCE Level III , prospect i ve case-control study Summary A prospect i ve study was carried out to test the sensitivity and specificity of stress radiography in detecting anterior cruciate ligament deficiency in both knees of 116 patients using the Telos device . In 47 of these a total or partial rupture of the anterior cruciate ligament was diagnosed by arthroscopy , while the ligament was intact in the remaining 69 patients . The mean difference in radiological translation between the injured and the normal knee was greater than 5 mm ( p<0.001 ) in those with anterior cruciate deficiency , and less than 3 mm in the others . A differential displacement of up to 3 mm was considered normal . The sensitivity of the method was less than 67 % and the specificity was 100 % . Clinical diagnosis had a sensitivity of 70.2 % and a specificity of 98.5 % . Our findings suggest that , although a differential translation of more than 3 mm can be diagnostic , smaller differences do not rule out anterior cruciate deficiency . RésuméLes auteurs ont réalisé une étude prospect i ve pour évaluer la sensibilité et la spécificité des radiographies en position forcée dans le diagnostic des insuffisances du ligament croisé antérieur ( LCA ) . Une radiographie en tiroir forcé des deux genoux a d'abord été faite , en utilisant l'appareil Telos , chez 116 patients devant subir une arthroscopie unilatérale . Chez 47 de ces patients une rupture totale ou partielle du LCA a été confirmée par arthroscopie , qui a montrée un ligament intact chez les 69 autres . La différence moyenne de translation entre le genou blessé et le genou sain a été supérieure à 5 mm ( p<0.001 ) chez les patients ayant une insuffisance du LCA et inférieure à 3 mm chez les autres ( une différence de 3 mm a été considérée comme normale ) . La sensibilité de la méthode a été de moins de 67 % et le spécificité de 100 % . L'examen clinique a une sensibilité de 70.2 % et une spécificité de 98.5 % . Ces résultats permettent de penser que , bien qu'une translation supérieure à 3 mm puisse avoir une valeur diagnostique , une moindre différence n'exclut pas une insuffisance du ligament croisé antérieur In a prospect i ve , consecutive , clinical and stress radiographical study , comprising 153 traumatic knee injuries , the value of stress radiographical measurements , gonylaxometry , was studied . Clinical evaluation , gonylaxometry and preoperative evaluation under general anaesthesia were carried out in that order . Then the operative findings were recorded as drawings on st and ard diagrams . These were used as a basis for evaluation of the preoperative tests . Of all the methods evaluated , gonylaxometry was found to provide the most accurate information regarding the knee injury . Very close to this result were the findings under general anaesthesia . Anterior drawer sign was measured gonylaxometrically when damage to the anterior cruciate ligament was present ; posterior drawer meant damage to the posterior cruciate ligament . Partial ruptures of cruciate ligaments did not allow antero-posterior displacements exceeding the critical levels of the test . Small positive medial instability was found with ruptures of profound medial structures , higher values with total rupture of the long superficial collateral b and , and still higher values when cruciate ligament ruptures were also present . The predictive values of a positive radiographical test were 100 per cent as regards medial instability and 98 per cent for drawer looseness . The predictive values of a negative test were 96 per cent for drawer and 92 per cent for medial instability . These figures are based on the total material . 95 per cent confidence limits are given INTRODUCTION The clinical diagnosis of the anterior cruciate ligament ( ACL ) tear is based on demonstrating anterior subluxation of the tibia on the femur . In any of the following perspectives , diagnostic ( cutoff value confirming rupture ) , prognostic ( treatment efficacy ) , and therapeutic ( laxity influencing the treatment ) , this laxity can be measured on stress X-rays . WORKING HYPOTHESIS The diagnostic value of dynamic radiographs is low for ACL rupture . Passive Telos ( ® ) X-rays have better diagnostic value , better radiologic quality , and are easier to carry out than active Franklin-type X-rays . MATERIAL AND METHODS A cohort of 112 patients ( 28 females , 84 males ; mean age , 33.7 years [ range , 18 - 72 years ] ) with an indication for knee arthroscopy were studied prospect ively . Before undergoing the arthroscopic treatment , two series of images of both knees were taken : one series of passive anterior drawer dynamic X-rays on a Telos ( ® ) device at 250 N and a series of active anterior drawer dynamic X-rays according to Franklin ( contraction of the quadriceps against 7 kg of weight at the ankle ) . The arthroscopic evaluation of the ACL ( reference status ) was compared to the anterior laxity measurements ( absolute and differential ) of each knee compartment ( medial , lateral , and average ) to determine the diagnostic value of the two radiological tests . RESULTS We found 70 patients with an " arthroscopically ruptured ACL " , 32 with an " arthroscopically healthy ACL " , and 10 with a " partial rupture " . The measurement of the anterior drawer values on the dynamic X-rays ( active and passive ) by two independent observers was reliable and reproducible ( ICC>0.80 ) , particularly when using the medial compartment ( ICC=0.96 ) and the differential values eliminating the interobserver measurement error and interindividual laxity variations . In terms of X-ray technique , the active images were more frequently painful and the radiographic result showed less good quality than the Telos images . The anterior drawer values in the " healthy ACL " group were significantly less than in the " ruptured ACL " group for the Telos ( ® ) images , whether the measurements were absolute or differential . For the Franklin images , this difference was only significant for the absolute values . Used for diagnosis ( 4-mm differential on the medial compartment ) , the passive dynamic images had lower diagnostic values ( Se=59 % and Sp=90 % ) than the series reported in the literature , which were marked by great heterogeneity . CONCLUSION The measurement of anterior drawer values on Telos ( ® ) and Franklin dynamic X-rays is a reliable and reproducible measurement , particularly when using the medial compartment and differential measurements . This small series did not demonstrate a diagnostic value for the Franklin images , contrary to the Telos ( ® ) X-rays . Used for diagnostic purpose s , the Telos ( ® ) images had a low sensitivity ; consequently , they should be used preferentially for prognostic or therapeutic purpose s. LEVEL OF EVIDENCE Level III , prospect i ve case-control study PURPOSE The objective of this study was to evaluate the efficacy of different stress radiography techniques in quantifying a posterior cruciate ligament ( PCL ) lesion . TYPE OF STUDY Prospect i ve serial study . METHODS Sixty patients with subacute or chronic PCL injuries , confirmed using magnetic resonance imaging ( MRI ) or arthroscopic evaluation , were enrolled in this study . The patients underwent a KT-2000 ( Medmetric , San Diego , CA ) examination and a series of stress radiographs that included a radiographic posterior drawer test with Telos ( Telos , Weterstadt , Germany ) at 90 degrees and 25 degrees of knee flexion , an active radiograph at 90 degrees of knee flexion , and an axial view radiograph . RESULTS Stress radiography performed with Telos showed an average posterior tibial displacement of 11.54 + /- 4.93 mm and 7.97 + /- 3.16 mm at 90 degrees and 25 degrees , respectively . The active radiographs showed an average posterior tibial displacement of 11.48 + /- 5.14 mm . CONCLUSIONS Stress radiographs were shown to be superior to arthrometric evaluation in quantifying posterior tibial translation . The techniques performed with the knee at 90 degrees of knee flexion allowed for greater posterior tibial displacement and , consequently , an easier quantification of the degree of ligament insufficiency . Stress radiographs performed through hamstring contraction gave the same results as those performed with Telos at 90 degrees of knee flexion Seventy-one consecutive patients with posterolateral knee injuries had clinical stability testing abnormalities documented prospect ively . We compared these find ings with the incidence and patterns of their injuries documented at surgery . An abnormal reverse pivot shift test was associated with injury to the fibular col lateral ligament ( P = 0.01 ) , popliteal components ( P = 0.01 ) , and midthird lateral capsular ligament ( P = 0.02 ) . An abnormal posterolateral external-rotation test at 30 ° of flexion was associated with injury to the fibular collateral ligament ( P = 0.0001 ) and lateral gastrocne mius tendon ( P = 0.01 ) . An abnormal adduction test at 30 ° of flexion was associated with injury to the poste rior arcuate ligament ( P = 0.02 ) . The results of this study should alert the clinician to the possibility of injury to a specific anatomic structure when the correspond ing clinical stability test is abnormal . Because the fib ular collateral ligament was injured in only 23 % of the knees in this large series of patients , we recommend that an injury to the fibular collateral ligament not be the sole determining factor in making the diagnosis of pos terolateral injuries . The wide array of injuries to many individual anatomic components that we found indi cates the complexity of injuries to the posterolateral aspect of the knee A hydraulically operated machine for applying well-defined forces to the knee joint is described . The measurement of anteroposterior as well as lateral and medial stability in the knee joint is based upon roentgenograms exposed while the forces are being exerted on the patient . The advantage of the radiological measuring method over methods using external measurements is the elimination of inaccuracies due to displacements of the soft tissues of the limb . The accuracy was evaluated by test/retest examination of 50 healthy subjects . The radiographs were measured at r and om after cessation of examinations in the gonylaxometer . The accuracy is + /- 1.2 nm for medial/lateral , + /- 2.4 nm for drawer sign . Diagnostically the difference between the two knees must exceed 2.0 nm ( collateral instability ) or 3.1 nm ( drawer ) to exceed st and ard values . The st and ard values for the different ligament laxities are given . The applied force to be used for evaluation of medial/lateral stability is recommended to be 9 kg , and for anteroposterior stability between 20 and 30 kg Background Stress radiography provides an objective tool to measure posterior knee instability . Intraobserver and interobserver reliability has been reported for the Telos device , but it has not been studied using the kneeling technique . Purpose This study was conducted to evaluate the intraobserver and interobserver reliability of measurements made using kneeling stress radiography to quantify posterior knee instability . Study Design Case series ( diagnosis ) ; Level of evidence , 4 . Methods One hundred thirty-two stress radiographs in 44 patients with suspected posterior knee instability were prospect ively taken using the kneeling technique . The amount of posterior displacement on the radiographs was then measured independently by 3 blinded testers ( an orthopaedic sports medicine faculty member , an orthopaedic chief resident , and a medical student ) on 2 separate occasions . Changes in mean and intraclass correlation coefficients ( ICCs ) were examined to assess the intraobserver and interobserver reliability of the measurements . Results Intraobserver changes in displacement means were small ( −0.307 mm , −0.294 mm , and + 0.035 mm ) and only significant for observer 1 . The combined intraobserver ICC was 0.973 for the 3 observers ( 0.976 , 0.959 , and 0.981 ) . Interobserver comparisons revealed significant differences in trial 1 between observers 2 and 3 ( 0.675 mm ) , no differences in trial 2 , and significant differences between observers 1 and 2 ( 0.333 mm ) and observers 2 and 3 ( 0.510 mm ) in the combined trial data . The combined interobserver ICC was 0.955 for the 3 observers ( 0.959 and 0.951 for the 2 trials ) . Conclusions The kneeling technique for posterior cruciate ligament stress radiography provides a reproducible method to quantify posterior knee instability INTRODUCTION Our knowledge on anterior cruciate ligament ( ACL ) pathomechanics has increased . The diagnosis of partial ACL tears must be accurate in order to adjust the operative planning to anatomic status and injury severity . Instrumented measurement of knee laxity is a useful preoperative tool to quantify anterior tibial translation and several laximetry tests are available . Yet , their accuracy remains to be established . HYPOTHESIS Clinical examination combined to instrumented laximetry with Telos ™ 15 kg and /or Rolimeter ™ would increase their sensitivity and specificity in the diagnosis of various ACL injury patterns . MATERIAL S AND METHODS One hundred and seventy-seven patients were prospect ively included . The ACL status was vali date d by arthroscopy . Around 69.5 % had a complete ACL tear and 30.5 % had a partial ACL tear . RESULTS Gross laxity with positive clinical tests was associated with complete ACL tears . Mean side-to-side difference was significantly greater with both laximetry methods in complete versus partial ACL tears . Laximetry results among different types of partial tears were not significantly different . Telos ™ results were consistent with gross laxity confirmed by pivot-shift test , while this was not recorded with Rolimeter ™ . Gross laxity with clinical tests and anterior tibial translation more than 5 mm with Telos ™ were substantially associated with complete ACL tears . DISCUSSION The combination of st and ard clinical examination with Telos ™ was more accurate than with Rolimeter ™ in the preoperative identification of the ACL injury pattern . Applying additional diagnostic tools can help the surgeon to preoperatively diagnose partial or complete ACL ruptures and propose an injury-specific surgical treatment . LEVEL OF EVIDENCE Level III ( case-control study ) |
1,245 | 26,812,502 | Administration of VDRAs increased serum creatinine levels .
Subgroup analysis of studies that did not use SCr-based measures did not indicate a lower GFR in the VDRA group . | BACKGROUND Vitamin D receptor activators ( VDRAs ) can protect against mineral bone disease , but they are reported to elevate serum creatinine ( SCr ) and may also reduce glomerular filtration rate ( GFR ) . | Abstract Objective . Left ventricular hypertrophy ( LVH ) is highly prevalent in chronic kidney disease ( CKD ) and a risk marker for cardiovascular mortality . It was hypothesized that vitamin D deficiency could play an important role in the pathogenesis of left ventricular hypertrophy and dysfunction in CKD . An open-labelled r and omized study was performed comparing the effect of alfacalcidol versus no treatment in patients with CKD 4 , secondary hyperparathyroidism and LVH . The primary endpoint was regression of LVH . Secondary endpoints were changes in left ventricular function . Material and methods . Twenty-four patients were screened . Of these , 14 had LVH according to the criteria used . Six were r and omized to alfacalcidol and seven to no treatment . The patient follow-up was 6 months . Left ventricular mass and function were measured by echocardiography . Results . Parathyroid hormone decreased by 72 % and –3 % in the alfacalcidol-treated and non-treated groups , respectively ( p < 0.05 ) , while serum Ca2 + increased by 9 % and –1.6 % , respectively ( p < 0.05 ) , and serum phosphate was unchanged . The left ventricular mass index was unchanged , whereas fractional shortening ( 20 % vs 2 % , p < 0.005 ) and Tei index ( 36 % vs 12 % , p < 0.05 ) increased significantly . Systolic and diastolic blood pressure was unchanged . Conclusion . Short-term treatment with alfacalcidol did not induce regression of LVH ; however , left ventricular function became hyperdynamic but less effective in patients with CKD . This could be problematic in the long term CONTEXT Decreased calcitriol production due to impaired renal function may be a significant risk factor for falls in normal aging population . OBJECTIVE The objective of the study was to examine the association between creatinine clearance ( CrCl ) and the incidence of falls and fallers in groups treated with placebo , calcitriol , estrogen therapy (ET)/estrogen + progestin therapy ( HT ) , and calcitriol + ET/HT . DESIGN This was a 3-yr , double-blind , placebo-controlled study design ed to test the efficacy of calcitriol and ET/HT on bone loss and falls with analysis by intention to treat and post hoc . SETTING The study was conducted at an academic outpatient center . PARTICIPANTS Four hundred eighty-nine normal elderly women aged 65 - 77 yr ; 415 women completed the study . INTERVENTION Subjects were r and omized to placebo , calcitriol 0.25 mug twice a day , ET daily ( conjugated equine estrogens 0.625 mg ) , HT ( conjugated equine estrogen 0.625 mg + medroxyprogesterone acetate 2.5 mg ) and calcitriol + ET/HT . MAIN OUTCOME MEASURES Cumulative number of falls and fallers were compared between groups with 24-h urine CrCl less than 60 and 60 ml/min or greater . RESULTS Calcitriol treatment decreased the number of fallers and falls . Low CrCl less than 60 ml/min was a predictor of the number of falls per person but not fallers in the placebo group ( P = 0.007 ) . In the low CrCl group ( < 60 ml/min ) , the rate of falls decreased on calcitriol by 53 % [ 95 % confidence interval ( CI ) -71 % to -22 % ; P = 0.003 ] , calcitriol + ET/HT by 61 % ( 95 % CI -76 % to -37 % ; P = 0.001 ) , and ET/HT by 25 % ( 95 % CI : -55 % to + 24 % ; not significant ) . Calcitriol reduced the rate of falls by 30 % ( 95 % CI -49 % to -4 % ; P = 0.027 ) in the CrCl 60 ml/min or greater group . CONCLUSION Calcitriol treatment decreases falls in all subjects but especially in elderly women with decreased renal function ( < 60 ml/min ) and frequent fallers Thirteen patients in the predialysis phase of chronic renal failure ( CRF ) were treated with calcitriol ( 0.25 micrograms/day ) and 12 with placebo . After 1 year of study , an increase in bone mineral density in the calcitriol group measured by dual-energy X-ray absorptiometry was seen for the femoral neck and lumbar spine when compared to the placebo group ( p < 0.001 and p < 0.01 , respectively ) . We conclude that a steady low dose of calcitriol started in the predialysis phase of CRF is beneficial to the patients with CRF . This may be partly due to suppression of secondary hyperparathyroidism BACKGROUND Higher doses of calcitriol are effective in lowering markedly elevated 1,84 PTH levels of patients with renal secondary hyperparathyroidism . It has not been established , however , whether prophylactic administration of low doses of calcitriol prevents an increase of 1,84 PTH without causing side-effects , i.e. hypercalcaemia , hypercalciuria , or hyperphosphataemia . STUDY DESIGN We carried out a placebo-controlled , double-blind prospect i ve multicentre trial over 12 months in 45 patients with mild to moderate renal failure . Criteria for inclusion were S-creatinine 1.4 mg/dl and 1,84 PTH > 6 pmol/l ( normal 6 ) . Calcitriol 0.125 microgram/day per os was compared with placebo . The patients received calcium carbonate per os if serum P exceeded 1.7 mmol/l . RESULTS Baseline 1,84 iPTH concentrations were not significantly different , i.e. 14.0 pmol/l ( 6.7 - 63.3 ) on placebo vs 16.2 ( 6.85 - 82.0 ) on calcitriol . Intention to treat analysis revealed a significant difference of final 1,84 iPTH , i.e. 27.8 ( 4.2 - 68.5 ) on placebo vs 18.2 ( 4.45 - 75.5 ) on calcitriol . On post-hoc analysis the difference was even more pronounced at S-creatinine concentrations above 3 mg/dl . S-calcium , S-phosphate , and urinary excretion of calcium did not change significantly on either placebo or on calcitriol . There were no episodes of hypercalcaemia or hyperphosphataemia . There was no significant difference of final S-creatinine or change in S-creatinine between placebo and calcitriol . One patient on calcitriol and two on placebo progressed to terminal renal failure . Bone alkaline phosphatase as a non-invasive index of bone metabolism was not decreased to subnormal levels . CONCLUSION The results document that a therapeutic window exists in patients with moderate renal failure and elevated of 1,84 iPTH , where low-dose calcitriol ( 0.125 microgram/day ) prevents the increase in 1,84 iPTH without causing side-effects . This observation suggests that the parathyroid is more sensitive to calcitriol than intestine and bone 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 The safety and efficacy of paricalcitol injection have been well established for the prevention and treatment of secondary hyperparathyroidism ( SHPT ) in patients with chronic kidney disease ( CKD ) stage 5 . The capsule form of paricalcitol was developed to provide a convenient dosage form for patients with stages 3 and 4 CKD . METHODS Three r and omized , placebo-controlled , phase-3 trials were conducted in patients with stages 3 and 4 CKD with SHPT . Enrollment criteria included an estimated glomerular filtration rate between 15 and 60 mL/min/1.73 m2 ( 0.25 and 1.00 mL/s/1.73 m2 ) , an average of 2 consecutive intact parathyroid hormone ( iPTH ) levels greater than 150 pg/mL ( ng/L ) , 2 consecutive serum calcium levels between 8.0 and 10.0 mg/dL ( 2.00 and 2.50 mmol/L ) , and 2 consecutive serum phosphorus levels of 5.2 mg/dL or less ( < or = 1.68 mmol/L ) . Two studies used a thrice-weekly dosing regimen and 1 study used a once-daily dosing regimen for 24 weeks . Dosing was based on serum iPTH , calcium , and phosphorus levels . The primary efficacy end point is 2 consecutive decreases in iPTH levels greater than 30 % from baseline . RESULTS Two hundred twenty patients participated ( n = 107 , paricalcitol ; n = 113 , placebo ) . At least 2 consecutive decreases in iPTH levels of 30 % or greater from baseline occurred in 91 % of paricalcitol versus 13 % of placebo patients ( P < 0.001 ) . Incidences of hypercalcemia , hyperphosphatemia , and elevated calcium-phosphorus product levels were not significantly different between groups . Similarly , no significant differences in urinary calcium and phosphorus excretion or deterioration in kidney function were detected in patients administered paricalcitol compared with placebo . CONCLUSION Paricalcitol capsule was well tolerated and effectively decreased iPTH levels with minimal or no impact on calcium levels , phosphorus balance , and kidney function in patients with stages 3 and 4 CKD OBJECTIVE To study the efficacy of synthetic 1,25 dihydroxyvitamin D3 ( calcitriol ) in the treatment of osteoporosis . DESIGN Two-year , double-blind , r and omized clinical trial . SETTING University medical center . PATIENTS Fifty postmenopausal women with vertebral fractures recruited by referral . INTERVENTION Calcium intake was adjusted to 25 mmol/d ( 1000 mg/d ) at baseline . Patients were then r and omized to treatment with either calcitriol or placebo . During the study , calcium intake was reduced to 15 mmol/d ( 600 mg/d ) and the dose of calcitriol was adjusted to maintain serum calcium less than 2.74 mmol/L ( less than 11.0 mg/dL ) or urine calcium less than 9.96 mmol/d ( less than 400 mg/d ) . MEASUREMENTS AND MAIN RESULTS After 2 years , the mean dose of calcitriol in the treated group was 0.62 micrograms/d . Bone mineral density of the spine increased 1.94 % with calcitriol therapy and decreased 3.92 % with placebo ( P = 0.001 ) . Total body calcium increased 0.21 % with calcitriol therapy and decreased 1.85 % with placebo ( P = 0.004 ) . Patients receiving placebo had significant decreases in spine density ( P = 0.0007 ) and total body calcium ( P = 0.0004 ) . There were no differences in vertebral fracture rates between the groups . Renal function studies were not statistically different between the groups after 2 years . CONCLUSION The treatment of postmenopausal osteoporotic women with synthetic calcitriol for 2 years was associated with increases in spine density and total body calcium . No adverse effects on renal function were seen after long-term calcitriol therapy BACKGROUND Bone loss occurs during the first 6 months after renal transplantation ( RT ) , and corticosteroid therapy plays an important role . Although calcium plus vitamin D administration prevents corticosteroid-induced osteoporosis , its use in RT recipients is limited by the risk of hypercalcemia . METHODS This double-blind , r and omized , and controlled prospect i ve intervention trial examined the effect of intermittent calcitriol ( 0.5 microg/48 h ) during the first 3 months after RT , plus oral calcium supplementation ( 0.5 g/day ) during 1 year with calcium supplementation alone . The primary outcome measure was the change in bone mineral density ( BMD ) at 3 and 12 months after RT ; we also explored whether the effect of calcitriol on BMD was different among vitamin D receptor ( VDR ) genotypes ( BsmI ) . Forty-five recipients were r and omized to calcitriol therapy ( CT ) and 41 were r and omized to placebo ( PL ) . RESULTS Both groups had a similar degree of pre-existing hyperparathyroidism ( 197 + /- 229 vs. 191 + /- 183 pg/mL ) , but a more pronounced decrease of parathyroid hormone ( PTH ) levels after RT was observed in CT patients ( at 3 months : 61.4 + /- 42.2 vs. 85.7 + /- 53.1 pg/mL , P= 0.02 ; at 12 months : 67.3 + /- 33.7 vs. 82.6 + /- 37 pg/mL ; P= 0.08 ) . CT patients preserved their BMD at the total hip significantly better than those on PL ( 3 months : 0.04 + /- 3.3 vs. -1.93 + /- 3.2 % , P= 0.01 ; 12 months : 0.32 + /- 4.8 vs. -2.17 + /- 4.4 % , P= 0.03 ) ; significant differences were noted at the intertrochanter , trochanter , and Ward 's triangle . Differences did not reach significance at the femoral neck . Two CT patients ( 4.4 % ) and 4 PL patients ( 9.8 % ) developed a hypercalcemic episode during the first 3 months after RT . The effect of CT on BMD at 3 months was more prominent in recipients with the at-risk allele of the VDR gene ( P= 0.03 ) . CONCLUSION Therapy with low-dose calcium supplements during 1 year , plus intermittent calcitriol for 3 months after RT , is safe , decreases PTH levels more rapidly , and prevents bone loss at the proximal femur ; a more pronounced effect is seen in recipients with at least one at-risk allele of the VDR genotype A decrease in bone mineral density ( BMD ) is a major complication of renal transplantation ( RTx ) , predominantly occurring within the first 6 mo after RTx . The most important causative factor is the use of corticosteroids , but persisting hyperparathyroidism and abnormalities in vitamin D metabolism play a role too . This study examines the effect of treatment with calcium and active vitamin D on the loss of BMD in the first 6 mo after RTx . A total of 111 renal transplant recipients ( 65 men , 46 women ; age , 47 + /- 13 yr ) were r and omized to either treatment with active vitamin D ( 0.25 microg/d ) plus calcium ( 1000 mg/d ) ( CaD group ) , or to no treatment ( NoT group ) . Immunosuppressive therapy consisted of cyclosporine , prednisone , and mycophenolate mofetil . Laboratory parameters and BMD ( lumbar spine and hip ) were measured at 0 , 1 ( laboratory only ) , 3 , and 6 mo after RTx . Lumbar BMD was nearly normal at the time of RTx . In both groups , a significant decrease in lumbar BMD was observed during the first 3 mo ( CaD , -3.3 + /- 4.3 % ; P < 0.0001 ; NoT , -4.1 + /- 4.8 % ; P < 0.0001 ) . Between the third day and sixth month , lumbar BMD slightly recovered in the CaD group , but it decreased further in the NoT group ( total loss 0 to 6 mo : CaD , -2.6 + /- 5.0 % [ P < 0.001 ] ; NoT , -5.0 + /- 4.7 % [ P < 0.0001 ] ) . As a result , the amount of bone loss at 6 mo was significantly lower in the CaD group ( P = 0.02 ) . Loss of BMD at the different femoral sites was also significantly reduced in the CaD group . Apart from a trend toward more frequent hypercalcemia in the CaD group , no clinical or biochemical differences existed between the groups . Treatment with a low dose of active vitamin D and calcium partially prevents bone loss at the lumbar spine and proximal femur during the first 6 mo after RTx STUDY OBJECTIVE To determine if calcitriol is an effective treatment in postmenopausal osteoporosis . DESIGN Double-blind , r and omized clinical trial of 2 years ' duration . SETTING University medical center with patients recruited by media announcements . PATIENTS Eighty-six postmenopausal women with vertebral compression fractures . INTERVENTIONS Patients were treated with calcitriol or placebo . Mean dose was 0.43 micrograms/d . Dietary calcium was 1000 mg/d ( 24.9 mmol/d ) . The medication dose and dietary calcium were adjusted for hypercalciuria or hypercalcemia . MEASUREMENTS AND MAIN RESULTS No significant differences between placebo and control groups were seen in the percent change in total body calcium ( 0.4 % + /- 1.0 compared with 0.0 % + /- 0.9 ) , single photon absorptiometry ( -0.5 % + /- 1.2 compared with -3.1 % + /- 0.9 ) or dual photon absorptiometry ( 0.0 % + /- 1.7 compared with -1.0 % + /- 2.2 ) . New fractures were seen in 16 % of the placebo group and 26 % of the calcitriol groups , so the difference in percent fractures was 10 % ( 95 % CI , -5.7 % to 25.7 % ) . Bone biopsies did not show changes in either group . The calcitriol group had significantly higher serum and urine calcium values , but renal function was not worse than in the placebo group . CONCLUSIONS Calcitriol is not an effective treatment for established postmenopausal osteoporosis Postkidney transplant hyperparathyroidism is a significant problem . Vitamin D receptor agonists are known to suppress parathyroid hormone ( PTH ) secretion . We examined the effect of oral paricalcitol on posttransplant secondary hyperparathyroidism by conducting an open label r and omized trial in which 100 incident kidney transplant recipients were r and omized 1:1 to receive oral paricalcitol , 2 μg per day , for the first year posttransplant or no additional therapy . Serial measurements of serum PTH , calcium and bone alkaline phosphatase , 24‐h urine calcium and bone density were performed . The primary endpoint was the frequency of hyperparathyroidism 1‐year posttransplant . Eighty‐seven patients completed the trial . One‐year posttransplant , 29 % of paricalcitol‐treated subjects had hyperparathyroidism compared with 63 % of untreated patients ( p = 0.0005 ) . Calcium supplementation was discontinued in two control and 15 treatment patients due to mild hypercalcemia or hypercalcuria . Paricalcitol was discontinued in four patients due to hypercalcuria/hypercalcemia and in one for preference . Two subjects required decreasing the dose of paricalcitol to 1 μg daily . Hypercalcemia was asymptomatic and reversible . Incidence of acute rejection , BK nephropathy and renal function at 1 year were similar between groups . Moderate renal allograft fibrosis was reduced in treated patients . Oral paricalcitol is effective in decreasing posttransplant hyperparathyroidism and may have beneficial effects on renal allograft histology Vitamin D receptor activation is associated with improved survival in patients with chronic kidney disease , but the mechanism of this benefit is unclear . To better underst and the effects of vitamin D on endothelial function , blood pressure , albuminuria , and inflammation in patients with chronic kidney disease ( 2 patients stage 2 , remaining stage 3 ) , we conducted a pilot trial in 24 patients who were r and omly allocated equally to 3 groups to receive 0 , 1 , or 2 & mgr;g of paricalcitol , a vitamin D analog , orally for 1 month . Placebo-corrected change in flow mediated dilatation with a 1-&mgr;g dose was 0.5 % and 0.4 % with a 2-&mgr;g dose ( P>0.2 ) . At 1 month , the treatment : baseline ratio of high sensitivity C-reactive protein was 1.5 ( 95 % CI : 1.1 to 2.1 ; P=0.02 ) with placebo , 0.8 ( 95 % CI : 0.3 to 1.9 ; P=0.62 ) with a 1-&mgr;g dose , and 0.5 ( 95 % CI : 0.3 to 0.9 ; P=0 . 03 ) with a 2-&mgr;g dose of paricalcitol . At 1 month , the treatment : baseline ratio of 24-hour albumin excretion rate was 1.35 ( 95 % CI : 1.08 to 1.69 ; P=0.01 ) with placebo , 0.52 ( 95 % CI : 0.40 to 0.69 ; P<0.001 ) with a 1-&mgr;g dose , and 0.54 ( 95 % CI : 0.35 to 0.83 ; P=0 . 01 ) with a 2-&mgr;g dose ( P<0.001 for between group changes ) . No differences were observed in iothalamate clearance , 24-hour ambulatory blood pressure , or parathyroid hormone with treatment or on washout . Thus , paricalcitol-induced reduction in albuminuria and inflammation may be mediated independent of its effects on hemodynamics or parathyroid hormone suppression . Long-term r and omized , controlled trials are required to confirm these benefits of vitamin D analogs To investigate the effect of calcitriol plus calcium carbonate on the bone loss associated with long-term renal transplantation , 30 patients with serum creatinine levels less than 2.0 mg/dL were r and omly allocated to a control ( n = 14 ) or treatment group ( n = 16 ) and studied with bone biopsy and densitometry at baseline and after 1 year of follow-up . Calcitriol ( 0.25 microg/d ) plus calcium carbonate ( 500 mg/d of elemental calcium ) were administered to patients in the treatment group . Comparing the baseline and final data of each group at a time , no change in bone mineral density ( BMD ) z score was observed at the distal radius ( control , -0.8 + /- 0.8 versus -0.6 + /- 0.9 ; treatment , -1.0 + /- 1.0 versus -1.0 + /- 1.1 ) . However , a significant increase ( P < 0.05 ) was found at the lumbar spine in both groups ( control , 0.1 + /- 1.6 versus 0.4 + /- 1.6 ; treatment , -0.1 + /- 1.5 versus 0.3 + /- 1.5 ) and only in the treatment group at the femoral neck ( control , -0.9 + /- 1.0 versus -0.8 + /- 1.0 ; treatment , -0.5 + /- 0.9 versus -0.3 + /- 1.1 ) . When BMD was compared between groups , no significant differences were observed at the evaluated anatomic sites at baseline or after 1 year of follow-up . After 1 year of follow-up , adjusting for age and sex ( z score ) , the control group showed a trend to reduce the value of several histomorphometric parameters , including osteoblast surface ( -2.2 + /- 6.1 versus -3.4 + /- 3.9 ) , osteoid surface ( -2.3 + /- 3.5 versus -3.1 + /- 3.9 ) , and osteoclast surface ( 0.2 + /- 5.0 versus -1.3 + /- 3.3 ) . Consequently , there was a significant reduction ( P < 0.05 ) in mineralizing surface ( -9.8 + /- 11.0 versus -15.8 + /- 12.3 ) and appositional rate ( -5.8 + /- 2.7 versus -7.6 + /- 2.2 ) . In the treatment group , a significant reduction ( P < 0.05 ) in osteoclast surface was observed at the end of the study ( 3.9 + /- 6.8 versus -1.2 + /- 4.1 ) , and although a trend to reduce osteoblast surface ( -2.5 + /- 2.6 versus -3.2 + /- 5.7 ) and osteoid surface ( -2.1 + /- 2.5 versus -3.2 + /- 2.8 ) was also found , patients maintained approximately the same level of wall thickness ( -5.2 + /- 5.3 versus -5.3 + /- 3.3 ) and bone volume ( -2.7 + /- 1.8 versus -2.5 + /- 1.7 ) . However , there was no improvement in mineralizing surface ( -4.2 + /- 2.9 versus -10.4 + /- 3.6 ) or appositional rate ( -5.8 + /- 3.1 versus -8.1 + /- 2.6 ) . No significant differences in bone histomorphometric variables were observed between groups after 1 year of follow-up . In conclusion , 1,25-dihydroxyvitamin D3 and calcium carbonate did not significantly improve bone loss in long-term renal transplant recipients . However , significant osteoclast suppression and a trend to maintain trabecular bone volume and wall thickness as well as improve the axial BMD were observed in the treatment group BACKGROUND The bone abnormalities that lead to symptomatic renal osteodystrophy commence early in the course of renal failure , but the optimal time to start treatment needs clarifying . The present study examined the effect of alfacalcidol treatment on bone metabolism and bone density in patients with pre-dialysis chronic renal failure ( CRF ) in a prospect i ve , r and omized , placebo-controlled double blind design . METHODS Repetitive measures of bone mineral density ( BMD ) estimated by dual energy X-ray absorptiometry and plasma levels of biochemical markers of bone turnover [ osteocalcin , bone alkaline phosphatase , propeptide of type-I collagen ( PICP ) and telopeptide of type-I collagen ] and parameters of calcium homeostasis were performed in 36 patients with a glomerular filtration rate ( GFR ) of 6 - 60 ml/min . RESULTS A significant difference in BMD between the treatment groups in favour of the alfacalcidol-treated patients was found in the spine ( 4.2 % ) , the femoral neck ( 4.9 % ) and the total femur ( 3.0 % ) ( P<0.05 ) . In the alfacalcidol group , plasma levels of parathyroid hormone 1 - 84 decreased from baseline values by 47+/-9 % , and p-osteocalcin and bone alkaline phosphatase decreased by 24+/-9 % and 48+/-8 % , respectively ( P<0.05 ) . In the placebo group , PICP increased by 32+/-26 % ( P<0.05 ) . No significant changes were found in plasma levels of vitamin D metabolites . GFR decreased significantly from baseline values in the alfacalcidol group ( by 28+/-4 ml/min ) and in the placebo group ( by 26+/-5 ml/min ) ( P<0.05 ) , with no difference being detected between the groups . CONCLUSIONS Long-term treatment with alfacalcidol is safe and might be beneficial for the preservation of bone mass in the pre-dialysis stages of CRF , most likely through a reduction in bone turnover as estimated from the changes of the biochemical bone markers Vitamin D seems to protect against cardiovascular disease , but the reported effects of vitamin D on patient outcomes in CKD are controversial . We conducted a prospect i ve , double blind , r and omized , placebo-controlled trial to determine whether oral activated vitamin D reduces left ventricular ( LV ) mass in patients with stages 3 - 5 CKD with LV hypertrophy . Subjects with echocardiographic criteria of LV hypertrophy were r and omly assigned to receive either oral paricalcitol ( 1 μg ) one time daily ( n=30 ) or matching placebo ( n=30 ) for 52 weeks . The primary end point was change in LV mass index over 52 weeks , which was measured by cardiac magnetic resonance imaging . Secondary end points included changes in LV volume , echocardiographic measures of systolic and diastolic function , biochemical parameters of mineral bone disease , and measures of renal function . Change in LV mass index did not differ significantly between groups ( median [ interquartile range ] , -2.59 [ -6.13 to 0.32 ] g/m(2 ) with paricalcitol versus -4.85 [ -9.89 to 1.10 ] g/m(2 ) with placebo ) . Changes in LV volume , ejection fraction , tissue Doppler-derived measures of early diastolic and systolic mitral annular velocities , and ratio of early mitral inflow velocity to early diastolic mitral annular velocity did not differ between the groups . However , paricalcitol treatment significantly reduced intact parathyroid hormone ( P<0.001 ) and alkaline phosphatase ( P=0.001 ) levels as well as the number of cardiovascular-related hospitalizations compared with placebo . In conclusion , 52 weeks of treatment with oral paricalcitol ( 1 μg one time daily ) significantly improved secondary hyperparathyroidism but did not alter measures of LV structure and function in patients with severe CKD In a prospect i ve , r and omized study , 66 osteoporotic postmenopausal women ( mean age , 67 years ) were scheduled to receive either alfacalcidol 0.25 microgram twice daily together with calcium 500 mg twice daily ( treatment group , n = 24 ) or placebo twice daily with calcium 500 mg twice daily ( control group , n = 42 ) for three years . In the treatment group , bone mineral content at the distal radius may have increased by 2 % compared to a significant decrease of 7.8 % in the control group . The difference between the two groups was also significant . Since the dose of alfacalcidol and calcium remained unadjusted , frequent hypercalciuria , as well as occasional mild , transient elevations of serum calcium , were observed in the treatment group . No changes in serum creatinine levels or creatinine clearance throughout the study were observed . The two groups did not differ with respect to the frequency of clinical side effects , which were mainly gastrointestinal and probably related to the calcium supplementation . Alfacalcidol and calcium may prevent further bone loss in women suffering from postmenopausal osteoporosis Abstract Objective : To determine whether alfacalcidol — used in management of overt renal bone disease — may safely prevent renal bone disease when used earlier in course of renal failure . Design : Double blind , prospect i ve , r and omised , placebo controlled study . Setting : 17 nephrology centres from Belgium , France , the Netherl and s , and the United Kingdom . Subjects : 176 patients aged 18–81 with mild to moderate chronic renal failure ( creatinine clearance 15–50 ml/min ) and with no clinical , biochemical , or radiographic evidence of bone disease . Interventions : Alfacalcidol 0.25 μg ( titrated according to serum calcium concentration ) or placebo given for two years . Main outcome measures : Quantitative histology of bone to assess efficacy of treatment and renal function to assess safety . Results : 132 patients had histological evidence of bone disease at start of study . Biochemical , radiographic , and histological indices of bone metabolism were similar for the 89 patients given alfacalcidol and the 87 controls given placebo . After treatment , mean serum alkaline phosphatase activity and intact parathyroid hormone concentration had increased by 13 % and 126 % respectively in controls but had not changed in patients given alfacalcidol ( P<0.001 ) . Hypercalcaemic episodes occurred in 10 patients given alfacalcidol ( but responded to decreases in drug dose ) and in three controls . Histological indices of bone turnover significantly improved in patients given alfacalcidol and significantly deteriorated in controls : among patients with abnormal bone histology before treatment , bone disease resolved in 23 ( 42 % ) of those given alfacalcidol compared with two ( 4 % ) of the controls ( P<0.001 ) . There was no difference in rate of progression of renal failure between the two groups . Conclusion : Early administration of alfacalcidol can safely and beneficially alter the natural course of renal bone disease in patients with mild to moderate renal failure . Key messages Key messages Treating such patients with alfacalcidol ( up to 1 μg/day for two years ) significantly improved their osteomalacia and hyperparathyroid disease Treatment had no apparent adverse effect on renal function Hypercalcaemic episodes were uncommon and readily responded to decreases in drug dose Alfacalcidol might be used more widely for patients with moderate renal failure not yet needing BACKGROUND Vitamin D has shown efficacy in the reduction of proteinuria in patients with chronic kidney disease . This study aim ed to determine the effect of calcitriol on urinary protein excretion in patients with immunoglobulin A ( IgA ) nephropathy . STUDY DESIGN Open-label , non-placebo-controlled , r and omized study . SETTING & PARTICIPANTS 50 patients with IgA nephropathy were enrolled . The main criterion for inclusion was urinary protein excretion > 0.8 g/d after renin-angiotensin system-inhibitor treatment for at least 3 months . INTERVENTION Patients were r and omly assigned ( 1:1 ) to receive 2 doses ( 0.5 μg ) of calcitriol per week or no treatment for 48 weeks . OUTCOMES The primary end point was to compare change in 24-hour urinary protein excretion from baseline to last measurement during treatment . MEASUREMENTS Every 8 weeks , there was measurement of 24-hour urinary protein excretion , serum calcium , serum phosphorus , serum creatinine , and intact parathyroid hormone . RESULTS Measurement of the primary end point showed changes in urinary protein excretion of + 21 % ( from 1.29 to 1.58 g/24 h ; 95 % CI , -9 % to + 52 % ) in the control group and -19 % ( from 1.60 to 1.30 g/24 h ; 95 % CI , -42 % to + 4 % ) in the calcitriol-treated group . There was a significant decrease in proteinuria in the calcitriol-treated group compared with the control group ( difference between groups , 41 % ; 95 % CI , 5%-79 % ; P = 0.03 ) . The secondary end point of achieving at least a 15 % decrease in proteinuria was attained by 7 of 24 ( 29 % ) controls and 17 of 26 ( 65 % ) of those treated with calcitriol ( P = 0.02 ) . No significant differences were observed in decrease in estimated glomerular filtration rate and change in blood pressure between the 2 groups . The incidence of recorded adverse events was similar between the 2 groups . LIMITATIONS Small and non-placebo-controlled study . CONCLUSIONS The addition of calcitriol to a renin-angiotensin system inhibitor result ed in a safe decrease in proteinuria in patients with IgA nephropathy Rapid bone loss after cardiac and lung transplantation results in an increased risk of osteoporotic fracture . This study examined the efficacy of treatment with calcitriol ( 1,25-dihydroxyvitamin D3 ) in preventing bone loss in patients undergoing cardiac or lung transplantation . In this 2-year double-blind , stratified study , 65 patients undergoing cardiac or single lung transplantation were r and omly allocated to receive either placebo or calcitriol ( 0.5 - 0.75 microg/day ) , the latter for either 12 months or 24 months . All patients received 600 mg calcium/day . Bone mineral density ( BMD ) was measured every 6 months for 2 years by dual-energy X-ray absorptiometry . There was no significant difference between groups with respect to age or cumulative dose of prednis(ol)one or cyclosporine over the 2 years . Bone loss at the proximal femur was significantly reduced or prevented at all three sites by treatment with calcitriol for 2 years compared with treatment with calcium alone . Treatment with calcitriol for 12 months followed by calcium for 12 months result ed in similar proximal femoral bone loss to that seen in those patients treated with calcium for 24 months , suggesting calcitriol prophylaxis needs to be continued beyond 12 months . At the lumbar spine , there were no significant differences in BMD between groups . Over a period of 2 years , 22 new vertebral fractures/deformities occurred in 4 patients treated with calcium alone compared with one new vertebral fracture in 1 patient treated with calcitriol . Because the sample size was too low to provide reliable interpretation of vertebral fracture rates , this difference is likely a chance result . Mild hypercalcemia was common with calcitriol therapy , as was mild hypercalciuria ( 59 % of patients vs. 10 % controls ) , but there were no significant differences between groups in serum creatinine after 2 years . These data suggest calcitriol has a role in reducing proximal femur bone loss after cardiac or lung transplantation but treatment needs to be continued beyond 1 year BACKGROUND We aim ed to investigate different treatment drugs for the prevention of post-transplant bone loss . METHODS Sixty adult male recent renal transplant recipients were enrolled into the study . Patients were r and omized into 4 groups : group I received daily alfacalcidol 0.5 microg PO ; group II received oral alendronate 5 mg/day ; group III received intranasal salmon calcitonin 200 IU every other day ; and group IV was considered a control group . Every patient was supplemented with daily 500 mg oral calcium carbonate . Parameters of bone metabolism were measured before and at 12 months after starting treatment . Bone mineral density ( BMD ) was measured by ( DEXA ) at lumber spine , femoral neck , and forearm before and after treatment period . RESULTS BMD was increased at lumber spine by 2.1 % , 0.8 % , 1.7 % , by 1.8 % , 0.6 % , 1.6 % at femoral neck , and by 3.2 % , 1.9 % , 2.6 % at forearm in groups I , II , and III , respectively , while it decreased by 3.2 % , 3.8 % , and 1.8 % at the same sites , respectively , in control group ( P= < 0.05 ) . iPTH level decreased significantly in group I , while the decrease was insignificant in other groups ( P= 0.003 ) . All other parameters were not statistically significant between treatment groups . Apart from transient hypocalcaemia in 3 patients in group II , and 2 patients in group III , no other significant adverse effects were noted . CONCLUSION This study proves that early bone loss that occurs during the first 12 months after renal transplantation could be prevented by alfacalcidol , calcitonin , or alendronate . Among the treatment groups , alfacalcidol significantly improved the hyperparathyroidism . All treatment drugs are safe and tolerable plaque‐type psoriasis has been successfully treated with oral calcitriol . but there has been no long‐term follow‐up on the safety and efficacy of this calciotropic hormone for psoriasis . In a single centre study , patients were enrolled in an open trial to evaluate the efficacy and safety of oral calcitriol for psoriasis . Of the 85 patients who received oral calcitriol , 88.0 % had some improvement in their disease : 26.5 , 36.2 and 25.3 % . had complete , moderate and slight improvement in their disease . respectively . The mean baseline psoriasis area severity index score ( PASI ) of 18 4 ± 1.0 was reduced to 9.7 ±0.8 and 7.8±1.3 after 6 and 24 months on oral calcitriol therapy . Serum calcium concentrations and 24 h urinary calcium excretion increased by 3.9 % and 148.2 % , respectively . but were not outside the normal range . Bone mineral density remained unchanged . The clearance of creatinine decreased by 13 4 % from baseline during the first 6 months of treatment , and thereafter . remained unchanged after 3 years of follow up . An evaluation of creatinine , inulin and para‐aminohypurate ( PAH ) clearance was performed in eight patients . After 6 months on oral calcitriol . there was a 22.5 % decline in creatinine clearance but no significant changes were observed in either inulin or PAH clearance , suggesting that calcitriol alters creatinine metabolism or secretion hut does not affect renal function . Oral calcitriol is effective and safe for the treatment of psoriasis BACKGROUND The progression of diabetic kidney disease ( DKD ) is highly correlated with proteinuria . Previous studies have suggested that vitamin D treatment may reduce proteinuria and has the potential to delay the progression of renal disease . OBJECTIVE To evaluate efficacy of oral calcitriol to decrease proteinuria in type 2 diabetic mellitus ( T2DM ) patients with DKD . MATERIAL AND METHOD In this 16-week , open label , prospect i ve , r and omized controlled study , 91 patients with T2DM with estimated glomerular filtration rate ( eGFR ) greater than 15 ml/min/1.73 m2 and urine protein to creatinine ratio ( UPCR ) greater than 1 g/g were enrolled . They were r and omly assigned to receive either oral calcitriol 0.5 mcg twice weekly ( n = 46 ) or without oral calcitriol ( n = 45 ) . The primary outcome was determined by the change of UPCR from baseline after 16 weeks of treatment of both groups . RESULTS At r and omization , the mean UPCR was 3.7 + 2.2 g/g in the calcitriol group and 3.4 + /- 2.1 g/g in the control group . The mean UPCR at 16-week follow-up was 2.9 + /- 1.7 g/g in the calcitriol group and 3.5 + /- 2.3 g/g in the control group . Percent changes in UPCR from baseline to the last evaluation in the calcitriol and control groups were -18.7 % and + 9.9 % ( p < 0.01 ) respectively . Patients with 30 % or more decrement in proteinuria occurred 43.5 % of the time in the calcitriol group and 11.1 % in the control group ( p < 0.01 ) . The eGFR and blood pressure did not differ significantly between the two groups . No serious adverse side effects were noted in either group . CONCLUSION Calcitriol treatment can reduce proteinuria in patients with DKD without serious adverse events This study represents the first r and omized prospect i ve , double-blind , placebo-controlled trial of the efficacy of 1,25(OH)2D3 on bone histology and serum biochemistry in patients with mild to moderate renal failure . Sixteen patients with chronic renal impairment ( creatinine clearance 20 to 59 ml per min ) received either 1,25(OH)2D3 , at a dose of 0.25 to 0.5 microgram daily ( eight patients ) , or placebo . Transiliac crest bone biopsies were performed before entrance into the study and after 12 months of experimental observation . None of the patients were symptomatic or had radiological evidence of bone disease . Of the thirteen patients who completed the study , initial serum 1,25(OH)2D levels were low in seven patients and parathyroid hormone levels were elevated in seven patients . Bone histology was abnormal in all patients . 1,25(OH)2D3 treatment was associated with a significant fall in serum phosphorus and alkaline phosphatase concentrations as well as with histological evidence of an amelioration of hyperparathyroid changes . In contrast to previous reports , no deterioration of renal function attributable to the treatment occurred , perhaps because a modest dose of 1,25(OH)2D3 was employed combined with meticulous monitoring . Further investigation is required to determine whether alternative therapeutic strategies ( smaller doses or intermittent therapy ) may avoid the potential for suppressing bone turnover to abnormally low levels in the long term CONTEXT Vitamin D is associated with decreased cardiovascular-related morbidity and mortality , possibly by modifying cardiac structure and function , yet firm evidence for either remains lacking . OBJECTIVE To determine the effects of an active vitamin D compound , paricalcitol , on left ventricular mass over 48 weeks in patients with an estimated glomerular filtration rate of 15 to 60 mL/min/1.73 m(2 ) . DESIGN , SETTING , AND PARTICIPANTS Multinational , double-blind , r and omized placebo-controlled trial among 227 patients with chronic kidney disease , mild to moderate left ventricular hypertrophy , and preserved left ventricular ejection fraction , conducted in 11 countries from July 2008 through September 2010 . INTERVENTION Participants were r and omly assigned to receive oral paricalcitol , 2 μg/d ( n = 115 ) , or matching placebo ( n = 112 ) . MAIN OUTCOME MEASURES Change in left ventricular mass index over 48 weeks by cardiovascular magnetic resonance imaging . Secondary end points included echocardiographic changes in left ventricular diastolic function . RESULTS Treatment with paricalcitol reduced parathyroid hormone levels within 4 weeks and maintained levels within the normal range throughout the study duration . At 48 weeks , the change in left ventricular mass index did not differ between treatment groups ( paricalcitol group , 0.34 g/m(2.7 ) [ 95 % CI , -0.14 to 0.83 g/m(2.7 ) ] vs placebo group , -0.07 g/m(2.7 ) [ 95 % CI , -0.55 to 0.42 g/m(2.7 ) ] ) . Doppler measures of diastolic function including peak early diastolic lateral mitral annular tissue velocity ( paricalcitol group , -0.01 cm/s [ 95 % CI , -0.63 to 0.60 cm/s ] vs placebo group , -0.30 cm/s [ 95 % CI , -0.93 to 0.34 cm/s ] ) also did not differ . Episodes of hypercalcemia were more frequent in the paricalcitol group compared with the placebo group . CONCLUSION Forty-eight week therapy with paricalcitol did not alter left ventricular mass index or improve certain measures of diastolic dysfunction in patients with chronic kidney disease . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00497146 BACKGROUND AND OBJECTIVE Disorders in bone mineral metabolism are common after kidney transplantation , covering , among other pathologic conditions , secondary hyperparathyroidism . Paricalcitol , a selective vitamin D receptor activator , is indicated in the prevention and treatment of secondary hyperparathyroidism . Recent evidence suggests that paricalcitol is also associated , by mechanisms not yet clarified , with improved patient survival . To clarify these unknown mechanisms , the aim of this study was to determine whether 3 months of treatment with paricalcitol modified the urinary peptidome of kidney transplant patients . METHODS This prospect i ve study included 42 stable kidney transplant patients , r and omized in 2 groups : a group treated with 1 μg/d paricalcitol ( n=25 ) and a control group that did not receive paricalcitol ( n=17 ) . Urine sample s of all patients were collected at baseline and after 3 months . The proteomic approach was based on magnetic bead technology coupled to MALDI-TOF mass spectrometry . RESULTS Paricalcitol treatment produced significant changes in urinary peptidome of kidney transplant patients . Variations in urinary peptides were independent of the degree of proteinuria and of the decrease in parathyroid hormone levels . CONCLUSIONS With this preliminary study , we obtained a profile of urinary peptides in which changes occurred due to treatment with paricalcitol . The identification of proteins to which these peptides belong may improve our knowledge about the possible pleiotropic effects of paricalcitol A controlled study of the effects of the potent vitamin-D metabolite , 1 , 25-dihydroxycholecalciferol ( 1,25[OH]2D3 ) , and vitamin D3 was done in 18 non-dialysed patients with chronic renal failure ( C.R.F. ) . Patients with a creatinine clearance below 35 ml/min and mild renal osteodystrophy were selected . After 6 months ' observation of the spontaneous course the patients were r and omly allocated to 6 months ' oral treatment with either 1 , 25 (OH)2D3 or vitamin D3 in initial daily doses of 1microgram and 4000 I.U. , respectively , combined with 0.5 g calcium . 1,25(OH)2D3 quickly corrected hypocalcaemia , reduced serum-alkaline-phosphatases and serum-immunoreactive-parathyroid-hormone , and more than doubled the urinary excretion rate of calcium . D3 had similar , but less pronounced effects . 7 out of 8 patients on 1,25(OH)2D3 , developed hypercalcaemia which necessitated a reduction in dosage . None of the patients on D3 treatment developed hypercalcaemia . The percentage fall in creatinine clearance was greater during treatment than before treatment in all patients on 1 , 25 (OH)2D3 ( P less than 0.01 ) and in 7 of 9 patients on vitamin D3 treatment ( though the group change here was not significant ) . Deterioration of renal function is a major limitation of the clinical use of 1 , 25(OH)2D3 and D3 in non-dialysed patients with C.R.F. In fact , the decrased formation of 1 , 25(OH)2D3 seen in C.R.F. might protect renal function at the expense of abnormalities in mineral metabolism BACKGROUND Despite treatment with renin – angiotensin – aldosterone system ( RAAS ) inhibitors , patients with diabetes have increased risk of progressive renal failure that correlates with albuminuria . We aim ed to assess whether paricalcitol could be used to reduce albuminuria in patients with diabetic nephropathy . METHODS In this multinational , placebo-controlled , double-blind trial , we enrolled patients with type 2 diabetes and albuminuria who were receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers . Patients were assigned ( 1:1:1 ) by computer-generated r and omisation sequence to receive 24 weeks ’ treatment with placebo,1 μg/day paricalcitol , or 2 μg/day paricalcitol . The primary endpoint was the percentage change in geometric mean urinary albumin-to-creatinine ratio ( UACR ) from baseline to last measurement during treatment for the combined paricalcitol groups versus the placebo group . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00421733 . FINDINGS Between February , 2007 , and October , 2008 , 281 patients were enrolled and assigned to receive placebo(n=93 ) , 1 μg paricalcitol ( n=93 ) , or 2 μg paricalcitol ( n=95 ) ; 88 patients on placebo , 92 on 1 μg paricalcitol , and 92 on2 μg paricalcitol received at least one dose of study drug , and had UACR data at baseline and at least one timepoint during treatment , and so were included in the primary analysis . Change in UACR was : –3 % ( from 61 to 60 mg/mmol;95 % CI –16 to 13 ) in the placebo group ; –16 % ( from 62 to 51 mg/mmol ; –24 to –9 ) in the combined paricalcitol groups , with a between-group difference versus placebo of –15 % ( 95 % CI –28 to 1 ; p=0.071 ) ; –14 % ( from 63 to 54 mg/mmol ; –24 to –1 ) in the 1 μg paricalcitol group , with a between-group difference versus placebo of –11%(95 % CI –27 to 8 ; p=0.23 ) ; and –20 % ( from 61 to 49 mg/mmol ; –30 to –8 ) in the 2 μg paricalcitol group , with a between-group difference versus placebo of –18 % ( 95 % CI –32 to 0 ; p=0.053 ) . Patients on 2 μg paricalcitol showed a nearly , sustained reduction in UACR , ranging from –18 % to –28 % ( p=0.014 vs placebo ) . Incidence of hypercalcaemia , adverse events , and serious adverse events was similar between groups receiving paricalcitol versus placebo . INTERPRETATION Addition of 2 μg/day paricalcitol to RAAS inhibition safely lowers residual albuminuria in patients with diabetic nephropathy , and could be a novel approach to lower residual renal risk in diabetes . FUNDING Abbott Very rapid bone loss , osteopenia , and osteoporosis have been documented in the first 6 to 12 mo after renal transplantation . Investigated was the effect of treatment with active vitamin D on the prevention of posttransplantation bone loss . Forty adult men who were recent renal transplant recipients were enrolled onto the study . Patients were r and omized into two groups : group 1 received daily alfacalcidol 0.5 micro g by mouth , and group 2 ( control ) received placebo . Every patient in both groups received daily 500-mg calcium carbonate supplements . Parameters of bone metabolism and bone mineral density measured at three sites were assessed before and after the study period . Bone mineral density was increased by 2.1 % , 1.8 % , and 3.2 % at lumbar spine , femoral neck , and forearm , respectively , in group 1 , whereas it decreased by 3.2 % , 3.8 % , and 1.8 % at the same sites in the control group ( P < 0.05 ) . Serum intact parathyroid hormone level decreased significantly in group 1 compared with the control group ( P = 0.003 ) . Early bone loss that occurs during the first 1 yr after renal transplantation could be prevented by alfacalcidol . Use of alfacalcidol early after transplantation is safe and well tolerated BACKGROUND Calcitriol lowers parathyroid hormone ( PTH ) levels in patients with chronic kidney disease ( CKD ) stages 3 and 4 , but its use is limited by a low therapeutic index and concerns regarding hypercalcemia and acceleration of kidney disease . We evaluated doxercalciferol ( 1alpha-hydroxyvitamin D2 ) as an alternative therapy in a r and omized , double-blinded , placebo-controlled , multicenter trial . METHODS Fifty-five adults with stage 3 or 4 CKD and an intact PTH ( iPTH ) level greater than 85 pg/mL ( ng/L ) completed 8 baseline weeks , followed by 24 weeks of oral therapy with doxercalciferol or placebo . Pretreatment demographics and biochemical features did not differ between groups . Dosages were increased gradually if iPTH level was not decreased by 30 % or greater and serum calcium and phosphorus levels were stable . Regular monitoring included plasma iPTH , serum calcium and phosphorus , urinary calcium , bone-specific serum markers , and serum lalpha,25-dihydroxyvitamin D levels . Glomerular filtration rate ( GFR ) was measured before and after treatment . RESULTS Mean plasma iPTH level decreased by 46 % from baseline after 24 weeks of doxercalciferol treatment ( P < 0.001 ) , but was unchanged with placebo . After 6 weeks , iPTH level reductions with doxercalciferol treatment exceeded those with placebo at all subsequent intervals ( P < 0.001 ) . No clinical ly significant differences in mean serum calcium or phosphorus or urinary calcium levels or incidence of hypercalcemia , hyperphosphatemia , or hypercalciuria were noted between groups . Serum C- and N-telopeptide and bone-specific alkaline phosphatase levels decreased with doxercalciferol treatment relative to both baseline and placebo ( P < 0.01 ) . Adverse-event rates and changes in GFR did not differ between groups . CONCLUSION Doxercalciferol is safe and effective in controlling secondary hyperparathyroidism of patients with CKD stages 3 and 4 The effects of a small dose of calcitriol ( less than or equal to 0.50 micrograms/day ) on parathyroid and renal function , bone histomorphometry , and aluminum ( Al ) metabolism were studied in a r and omized double blind study of 30 patients with predialysis chronic renal failure . The patients were followed at least monthly for 8 months . Serum Al levels were measured , and transiliac bone biopsies , double labeled with tetracycline , were obtained at both the beginning and end of the 8-month treatment period . Serum calcium and ionized calcium concentrations increased in the treatment group , and the calcitriol dosage had to be reduced in 8 patients at least once because of hypercalcemia . Calcitriol treatment did not significantly influence either serum A1 levels or the presence of stainable Al in bone . Serum PTH , urinary cAMP excretion , and bone resorption indices decreased in the treatment group , indicating suppression of parathyroid hyperfunction . Throughout the study renal function decreased at a similar rate in both groups , suggesting that calcitriol treatment had no depressive effect on renal function . We conclude that a low dose of calcitriol may be used to preserve or even restore bone metabolism in patients with predialysis chronic renal failure if serum calcium is closely followed and hypercalcemia promptly treated Calcitriol was compared with placebo in the treatment of postmenopausal osteoporosis in a double-blind , r and omized , parallel clinical trial of 24 months ' duration . Adjustment was made in dietary calcium to maximize the dose of calcitriol . The study was completed by 15 patients who received placebo and 12 patients who received calcitriol . The calcitriol group had positive slopes ( compared with negative slopes for the placebo group ) for total body calcium , bone mineral content of the radius , bone mineral density of the lumbar spine , and radiographic absorptiometry of the middle phalanges . The difference between the two groups was statistically significant for each of these measurements . The fracture rate in the treatment group was 250 per 1,000 patient-years as compared with 333 for the placebo group . The mean dose of calcitriol was 0.8 micrograms per day . Hypercalcemia , hypercalciuria , and perhaps nephrolithiasis were observed as complications of treatment . Calcitriol increased bone mineral density by decreasing bone resorption , but not by increasing bone formation . Future studies should concentrate on treatment with oral calcitriol in lower doses . It would also be of interest to examine parenteral administration of calcitriol . It is possible that bone formation can be increased by achieving higher serum levels of the drug , whereas complications may be avoided by using a non-oral route of administration 24 patients with chronic renal failure ( glomerular filtration-rate ( G.F.R. ) 5 - 25 ml/min ) participated in a double-blind placebo-controlled trial of the effects of 1 alpha-hydroxycholecalciferol ( 1alpha-H.C.C. ) 1 mug daily for eleven weeks . This treatment induced significant increases in the intestinal absorption of calcium and in plasma-calcium which reached normal levels within two weeks . It also induced a significant reduction of the raised serum levels of parathyroid hormone . No significant changes were induced in plasma-phosphorus , plasma-alkaline-phosphatase , or in the degree of bone mineralisation as measured by the phosphorus/hydroxyproline ratio in bone . The bone mineral content in the forearm measured by photon absorptiometry decreased to the same extent in the 1alpha-H.C.C. groups and in the placebo group . The fall in G.F.R. over eleven weeks was 2 - 5 times greater in the 1alpha-H.C.C. group than in the placebo group , but this difference was not significant . It is concluded that 1alpha-H.C.C. treatment in chronic renal failure does not affect the progressive loss of calcium from bone despite normalisation of plasma-calcium Vitamin D receptor activation has been associated with increased serum creatinine and reduced estimated glomerular filtration rates , raising concerns that its use may be detrimental to kidney function . Here we studied the effect of vitamin D receptor activation on serum creatinine , creatinine generation , and its clearance . We measured baseline serum creatinine and 24-h urine creatinine in 16 patients with chronic kidney disease . The measurements were repeated every day for 7 days , during which time the patients received 2 μg paricalcitol , an orally active vitamin D receptor activator , every morning . At 4 days after stopping the vitamin analog , measurements were continued for 3 days . Geometric mean parathyroid hormone levels decreased from 77 pg/ml at baseline to 43 pg/ml at the end of treatment and significantly rebounded to 87 pg/ml following paricalcitol withdrawal , thereby supporting the biological efficacy of the analog dose used . With this therapy , the serum creatinine significantly increased at a rate of 0.010 mg/dl/day and urine creatinine at a rate of 17.6 mg/day . Creatinine and iothalamate clearances did not change , whereas urine albumin decreased insignificantly . Thus , short-term vitamin D receptor activation increases creatinine generation and serum creatinine , but it does not influence the glomerular filtration rate |
1,246 | 16,625,595 | There was no convincing evidence from the trials identified that blood pressure lowering prevents the development of dementia or cognitive impairment in hypertensive patients with no apparent prior cerebrovascular disease . | BACKGROUND Hypertension and cognitive impairment are prevalent in older people .
It is known that hypertension is a direct risk factor for vascular dementia and recent studies have suggested hypertension also impacts upon prevalence of Alzheimer 's disease .
The question is therefore whether treatment of hypertension lowers the rate of cognitive decline .
OBJECTIVES To assess the effects of blood pressure lowering treatments for the prevention of dementia and cognitive decline in patients with hypertension but no history of cerebrovascular disease . | A substantial number of older hypertensive patients have stage 1 isolated systolic hypertension ( systolic blood pressure between 140 and 159 mm Hg and diastolic blood pressure < 90 mm Hg ) , but there are currently no data showing that drug treatment is effective , safe , and /or beneficial . To compare the effects of active treatment compared with placebo on blood pressure , left ventricular hypertrophy , and quality of life among older stage 1 isolated systolic hypertensive patients , a r and omized , double-blind , parallel-group , multicenter clinical trial comparing felodipine ( 2.5 , 5 , or 10 mg once daily ) and matching placebo was performed in 171 patients ( 49 % male , average age 66±7 years , with 49 % white and 30 % Hispanic ) with a baseline blood pressure of 149±7/83±6 mm Hg . During 52 weeks of treatment , patients r and omized to active treatment achieved significantly lower blood pressures ( 137.0±11.7/80.2±7.6 mm Hg for extended-release felodipine versus 147.5±16.0/83.5±9.7 mm Hg for placebo , P < 0.01 for each ) , a reduced incidence of left ventricular hypertrophy ( 7 % for extended release felodipine versus 24 % for placebo , P < 0.04 ) , and improved quality of life ( change in Psychological General Well-Being index , 3.0±6.8 for extended-release felodipine versus −0.8±10.3 for placebo , P < 0.01 ) versus baseline . There were no clinical ly significant differences between treatments in tolerability or adverse effects . Stage 1 isolated systolic hypertension can be effectively and safely treated pharmacologically . Treatment reduced progression to the higher stages of hypertension , reduced the incidence of left ventricular hypertrophy , and improved an overall measure of the quality of life . Larger and longer studies will be needed to document any long-term reduction in cardiovascular event rates associated with treating stage 1 systolic hypertension Although the benefits of antihypertensive treatment in " young " elderly ( under 70 years ) hypertensive patients are well established , the value of treatment in older patients ( 70 - 84 years ) is less clear . The Swedish Trial in Old Patients with Hypertension ( STOP-Hypertension ) was a prospect i ve , r and omised , double-blind , intervention study set up to compare the effects of active antihypertensive therapy ( three beta-blockers and one diuretic ) and placebo on the frequency of fatal and non-fatal stroke and myocardial infa rct ion and other cardiovascular death in hypertensive Swedish men and women aged 70 - 84 years . We recruited 1627 patients at 116 health centres throughout Sweden , who were willing to participate , and who met the entry criteria of three separate recordings during a 1-month placebo run-in period of systolic blood pressure between 180 and 230 mm Hg with a diastolic pressure of at least 90 mm Hg , or a diastolic pressure between 105 and 120 mm Hg irrespective of the systolic pressure . The total duration of the study was 65 months and the average time in the study was 25 months . 812 patients were r and omly allocated active treatment and 815 placebo . The mean difference in supine blood pressure between the active treatment and placebo groups at the last follow-up before an endpoint , death , or study termination was 19.5/8.1 mm Hg . Compared with placebo , active treatment significantly reduced the number of primary endpoints ( 94 vs 58 ; p = 0.0031 ) and stroke morbidity and mortality ( 53 vs 29 ; p = 0.0081 ) . Although we did not set out to study an effect on total mortality , we also noted a significantly reduced number of deaths in the active treatment group ( 63 vs 36 ; p = 0.0079 ) . The benefits of treatment were discernible up to age 84 years . We conclude that antihypertensive treatment in hypertensive men and women aged 70 - 84 confers highly significant and clinical ly relevant reductions in cardiovascular morbidity and mortality as well as in total mortality BACKGROUND Stevioside , a natural glycoside isolated from the plant Stevia rebaudiana Bertoni , has been used as a commercial sweetening agent in Japan and Brazil for > 20 years . Previous animal and human studies have indicated that stevioside has an antihypertensive effect . OBJECTIVES This study was undertaken to investigate the long-term ( 2-year ) efficacy and tolerability of stevioside in patients with mild essential hypertension . Secondary objectives were to determine the effects of stevioside on left ventricular mass index ( LVMI ) and quality of life ( QOL ) . METHODS This was a multicenter , r and omized , double-blind , placebo-controlled trial in Chinese men and women aged between 20 and 75 years with mild essential hypertension ( systolic blood pressure [ SBP ] 140 - 159 mm Hg and diastolic blood pressure [ DBP ] 90 - 99 mm Hg ) . Patients took capsules containing 500 mg stevioside powder or placebo 3 times daily for 2 years . Blood pressure was measured at monthly clinic visits ; patients were also encouraged to monitor blood pressure at home using an automated device . LVMI was determined by 2-dimensional echocardiography at baseline and after 1 and 2 years of treatment . QOL was assessed using the Medical Outcomes Study 36-Item Short-Form Health Survey . Electrocardiographic , laboratory , and QOL parameters were assessed at the beginning of treatment , and at 6 months , 1 year , and 2 years . RESULTS One hundred seventy-four patients ( 87 men , 87 women ) were enrolled in the study , and 168 completed it : 82 ( 42 men , 40 women ; mean [ SD ] age , 52 [ 7 ] years ) in the stevioside group and 86 ( 44 women , 42 men ; mean age , 53 [ 7 ] years ) in the placebo group . After 2 years , the stevioside group had significant decreases in mean ( SD ) SBP and DBP compared with baseline ( SBP , from 150 [ 7.3 ] to 140 [ 6.8 ] mm Hg ; DBP , from 95 [ 4.2 ] to 89 [ 3.2 ] mm Hg ; P < 0.05 ) and compared with placebo ( P < 0.05 ) . Based on patients ' records of self-monitored blood pressure , these effects were noted beginning approximately 1 week after the start of treatment and persisted throughout the study . There were no significant changes in body mass index or blood biochemistry , and the results of laboratory tests were similar in the 2 groups throughout the study . No significant difference in the incidence of adverse effects was noted between groups , and QOL scores were significantly improved overall with stevioside compared with placebo ( P < 0.001 ) . Neither group had a significant change in mean LVMI . However , after 2 years , 6 of 52 patients ( 11.5 % ) in the stevioside group had left ventricular hypertrophy ( LVH ) , compared with 17 of 50 patients ( 34.0 % ) in the placebo group ( P < 0.001 ) . Of those who did not have LVH at baseline , 3 of 46 patients ( 6.5 % ) in the stevioside group had developed LVH after 2 years , compared with 9 of 37 patients ( 24.3 % ) in the placebo group ( P < 0.001 ) . CONCLUSIONS In this 2-year study in Chinese patients with mild hypertension , oral stevioside significantly decreased SBP and DBP compared with placebo . QOL was improved , and no significant adverse effects were noted Summary The Syst-Eur Trial is a concerted action of the European Community ’s Medical and Health Research Programme . The trial is carried out in consultation with the World Health Organization , the International Society of Hypertension , the European Society of Hypertension and the World Hypertension League . This article describes the objectives and the protocol of Syst-Eur , a multicentre trial design ed by the European Working Party on High Blood . Pressure in the Elderly ( EWPHE ) , to test the hypothesis that antihypertensive treatment of elderly patients with isolated systolic hypertension results in a significant change in stroke morbidity and mortality . Secondary endpoints include cardiovascular events , such as myocardial infa rct ion and congestive heart failure . To be eligible patients must be at least 60 years old and have a systolic blood pressure averaging 160–219 mmHg with a diastolic pressure less than 95 mmHg . Patients must give their informed consent and be free of major cardiovascular and non-cardiovascular diseases at entry . The patients are r and omized to active treatment or placebo . Active treatment consists of nitrendipine ( 10–40 mg/day ) , combined with enalapril ( 5–20 mg/day ) and hydrochlorothiazide ( 12.5–25 mg/day ) , as necessary . The patients of the control group receive matching placebos . The drugs ( or matching placebos ) are stepwise titrated and combined in order to reduce systolic blood pressure by 20 mmHg at least to a level below 150 mmHg . Morbidity and mortality are monitored to enable an intention-to-treat and per protocol comparison of the outcome in the 2 treatment groups . A one-year pilot trial ( 1989 ) showed that the protocol is practicable . The Ethics Committee therefore decided to start the definite study ( 1990 ) , in which r and omized patients will be followed for 5 years . Recruitment of new centres and of the required 3,000 patients will last 3 years ( until 1993 ) Objective To compare quality of life in elderly patients with isolated systolic hypertension allocated r and omly to groups to receive placebo or active treatment in the Systolic Hypertension in the Elderly Trial . Design Double-blind r and omized controlled trial . Methods Patients aged 60 years were allocated r and omly to groups to receive first-line treatment with nitrendipine ( with second- and third-line enalapril and hydrochlorothiazide ) or placebo . Trained interviewers administered trail-making tests ( Trail A and B ) , Brief Assessment Index ( a measure of depressed mood ) and four subscales from the Sickness Impact Profile ( Ambulation , Social Interaction , Sleep and Rest , and Home work ) . Results Six hundred and ten patients completed a baseline and at least one follow-up question naire . Trail-making scores were slower in actively treated patients , especially in the first 6 months of follow-up when the between-group effect sizes were 0.25 [ 95 % confidence interval ( CI ) 0.07 to 0.43 ] for Trail-making A and 0.13 ( 95 % CI −0.05 to 0.31 ) for Trail-making B. Across the 4 years of follow-up , patients receiving active treatment were more likely to report problems on the Social Interaction scale than were placebo-treated patients ( odds ratio 1.32 , 95 % CI 1.02 to 1.69 ) , equivalent to a 7 % difference . There were no significant differences between active and placebo treatment in the other Sickness Impact Profile dimensions or in the measure of depression . Conclusions Active treatment in the Systolic Hypertension in Europe trial was associated with some small adverse impacts on quality of life BACKGROUND Results of previous studies of white older adults suggest that antihypertensive medications preserve cognition . We assessed the long-term effect of antihypertensive medications on cognitive function in a community sample of African American older adults . METHODS We conducted longitudinal surveys and clinical assessment of cognitive function in a r and om sample of 2212 community-dwelling African Americans 65 years and older . We identified 1900 participants without evidence of cognitive impairment at baseline , 1617 of whom had subsequent follow-up information , and 946 of whom had blood pressure measurements . Cognitive function was measured at baseline and at 2 and 5 years by means of scores on the Community Screening Instrument for Dementia and neuropsychological and clinical assessment for dementia and cognitive impairment . Prescription and nonprescription medication use was derived from in-home inspection of medications and participant and informant reports . RESULTS Of 1900 participants , 288 ( 15.2 % ) developed incident cognitive impairment . Using logistic regression to control for the effects of age , sex , education , baseline cognitive scores , and hypertension and angina or myocardial infa rct ion , we found that antihypertensive medications reduced the odds of incident cognitive impairment by 38 % ( odds ratio , 0.62 ; 95 % confidence interval , 0.45 - 0.84 ) . Corresponding analysis using blood pressure measurements on the subset of participants was inconclusive . CONCLUSION Antihypertensive medication use is associated with preservation of cognitive function in older African American adults The Study on COgnition and Prognosis in the Elderly ( SCOPE ) was a multinational , r and omised , double-blind study to assess the effects of c and esartan 8–16 mg daily on cardiovascular events and cognitive function in elderly patients ( aged 70–89 years ) with mild to moderate hypertension . A total of 4937 patients were r and omised to c and esartan or placebo with other antihypertensive drugs ( mostly diuretics , beta-blockers , and calcium antagonists ) added as needed to control blood pressure . Only 16 % of the patients in the control group received placebo alone . The mean follow-up was 3.7 years . The aim of this health-related quality of life ( HRQL ) sub study analysis was to investigate changes in HRQL during antihypertensive treatment , and possible differences in patients receiving c and esartan-based or other antihypertensive treatment . Three vali date d HRQL instruments were used : the Psychological General Well-being ( PGWB ) Index , the Subjective Symptoms Assessment Profile ( SSA-P ) , and the EuroQoL Health Utility Index ( EuroQoL ) . The HRQL was generally good at baseline and well preserved during follow-up in the presence of substantial blood pressure reductions in both treatment groups . Several of the observed changes in score from baseline to last visit favoured c and esartan-based compared to control treatment , particularly the changes in PGWB Anxiety ( –0.5 vs −1.0 , P=0.01 ) , PGWB Positive well-being ( –0.8 vs −1.1 , P=0.04 ) , SSA-P Cardiac symptoms ( 0.03 vs 0.10 , P=0.03 ) , and EuroQoL Current health ( −3.1 vs −5.3 , P=0.008 ) . This favourable result may be related to the somewhat lower blood pressure associated with c and esartan-based treatment . In conclusion , there should be no reason to withhold modern antihypertensive therapy in elderly patients due to concerns for a negative effect on HRQL BACKGROUND The Valsartan Antihypertensive Long-term Use Evaluation ( VALUE ) trial was design ed to test the hypothesis that for the same blood-pressure control , valsartan would reduce cardiac morbidity and mortality more than amlodipine in hypertensive patients at high cardiovascular risk . METHODS 15?245 patients , aged 50 years or older with treated or untreated hypertension and high risk of cardiac events participated in a r and omised , double-blind , parallel-group comparison of therapy based on valsartan or amlodipine . Duration of treatment was event-driven and the trial lasted until at least 1450 patients had reached a primary endpoint , defined as a composite of cardiac mortality and morbidity . Patients from 31 countries were followed up for a mean of 4.2 years . FINDINGS Blood pressure was reduced by both treatments , but the effects of the amlodipine-based regimen were more pronounced , especially in the early period ( blood pressure 4.0/2.1 mm Hg lower in amlodipine than valsartan group after 1 month ; 1.5/1.3 mm Hg after 1 year ; p<0.001 between groups ) . The primary composite endpoint occurred in 810 patients in the valsartan group ( 10.6 % , 25.5 per 1000 patient-years ) and 789 in the amlodipine group ( 10.4 % , 24.7 per 1000 patient-years ; hazard ratio 1.04 , 95 % CI 0.94 - 1.15 , p=0.49 ) . INTERPRETATION The main outcome of cardiac disease did not differ between the treatment groups . Unequal reductions in blood pressure might account for differences between the groups in cause-specific outcomes . The findings emphasise the importance of prompt blood-pressure control in hypertensive patients at high cardiovascular risk BACKGROUND Systolic hypertension increases the risk of dementia in elderly people . The vascular dementia project , set up in the framework of the double-blind placebo-controlled Systolic Hypertension in Europe ( Syst-Eur ) trial , investigated whether antihypertensive drug treatment could reduce the incidence of dementia . METHODS Eligible patients had no dementia , were at least 60 years old , and had a blood pressure when seated of 160 - 219 mm Hg systolic and below 95 mm Hg diastolic . Active treatment consisted of nitrendipine ( 10 - 40 mg/day ) with the possible addition of enalapril ( 5 - 20 mg/day ) , hydrochlorothiazide ( 12.5 - 25 mg/day ) , or both drugs , titrated or combined to reduce the systolic blood pressure by at least 20 mm Hg to reach a value below 150 mm Hg . Cognitive function was assessed by the mini mental state examination ( MMSE ) . If the MMSE score was 23 or less , diagnostic tests for dementia were done ( DSM-III-R criteria ) . The cause of dementia was established by the modified ischaemic score with brain imaging or the Hachinski score . FINDINGS Median follow-up by intention to treat was 2.0 years . Compared with placebo ( n=1180 ) , active treatment ( n=1238 ) reduced the incidence of dementia by 50 % from 7.7 to 3.8 cases per 1000 patient-years ( 21 vs 11 patients , p=0.05 ) . The median MMSE score at r and omisation was 29 in both treatment groups . At the last available assessment , systolic and diastolic blood pressure were , respectively , 8.3 mm Hg and 3.8 mm Hg lower ( p<0.001 ) in the active-treatment group , but on average the MMSE scores did not change in either group . In the control patients , however , the MMSE decreased ( p=0.04 ) with decreasing diastolic blood pressure , whereas in the active-treatment group MMSE scores improved slightly ( p=0.01 ) with greater reduction in diastolic blood pressure ( p=0.002 for between-group difference ) . INTERPRETATION In elderly people with isolated systolic hypertension , antihypertensive treatment was associated with a lower incidence of dementia . If 1000 hypertensive patients were treated with antihypertensive drugs for 5 years 19 cases of dementia might be prevented Background The prognostic benefits of blood pressure lowering treatment in elderly hypertensive patients were established more than a decade ago , but are less clear in those with mildly to moderately elevated blood pressure . Objective To assess whether c and esartan-based antihypertensive treatment in elderly patients with mildly to moderately elevated blood pressure confers a reduction in cardiovascular events , cognitive decline and dementia . Design Prospect i ve , double-blind , r and omized , parallel-group study conducted in 1997–2002 . Setting and participants The study was of 4964 patients aged 70–89 years , with systolic blood pressure 160–179 mmHg , and /or diastolic blood pressure 90–99 mmHg , and a Mini Mental State Examination ( MMSE ) test score ⩾ 24 . A total of 527 centres in 15 countries participated in the study . Intervention Patients were assigned r and omly to receive the angiotensin receptor blocker c and esartan or placebo , with open-label active antihypertensive therapy added as needed . As a consequence , active antihypertensive therapy was extensively used in the control group ( 84 % of patients ) . Mean follow-up was 3.7 years . Main outcome measures The primary outcome measure was major cardiovascular events , a composite of cardiovascular death , non-fatal stroke and non-fatal myocardial infa rct ion . Secondary outcome measures included cardiovascular death , non-fatal and fatal stroke and myocardial infa rct ion , cognitive function measured by the MMSE and dementia . Results Blood pressure fell by 21.7/10.8 mmHg in the c and esartan group and by 18.5/9.2 mmHg in the control group . A first major cardiovascular event occurred in 242 c and esartan patients and in 268 control patients ; risk reduction with c and esartan was 10.9 % [ 95 % confidence interval ( CI ) , −6.0 to 25.1 , P = 0.19 ] . C and esartan-based treatment reduced non-fatal stroke by 27.8 % ( 95 % CI , 1.3 to 47.2 , P = 0.04 ) , and all stroke by 23.6 % ( 95 % CI , −0.7 to 42.1 , P = 0.056 ) . There were no significant differences in myocardial infa rct ion and cardiovascular mortality . Mean MMSE score fell from 28.5 to 28.0 in the c and esartan group and from 28.5 to 27.9 in the control group ( P = 0.20 ) . The proportions of patients who had a significant cognitive decline or developed dementia were not different in the two treatment groups . Conclusions In elderly hypertensive patients , a slightly more effective blood pressure reduction during c and esartan-based therapy , compared with control therapy , was associated with a modest , statistically non-significant , reduction in major cardiovascular events and with a marked reduction in non-fatal stroke . Cognitive function was well maintained in both treatment groups in the presence of substantial blood pressure reductions . Both treatment regimens were generally well tolerated BACKGROUND Little information has been published on the impact of antihypertensive medications on quality of life in older persons . Particular concern has existed that lowering systolic blood pressure in older persons might have adverse consequences on cognition , mood , or leisure activities . METHODS A multicenter double-blind r and omized controlled trial was conducted over an average of 5 years ' followup involving 16 academic clinical trial clinics . Participants consisted of 4736 persons ( 1.06 % ) selected from 447,921 screenees aged 60 years and older . Systolic blood pressure at baseline ranged from 160 to 219 mm Hg , while diastolic blood pressure was less than 90 mm Hg . Participants were r and omized to active antihypertensive drug therapy or matching placebo . Active treatment consisted of 12.5 to 25 mg of chlorthalidone for step 1 , while step 2 consisted of 25 to 50 mg of atenolol . If atenolol was contraindicated , 0.05 to 0.10 mg of reserpine could be used for the second-step drug . The impact of drug treatment on measures of cognitive , emotional , and physical function and leisure activities was assessed . RESULTS Our analyses demonstrate that active treatment of isolated systolic hypertension in the Systolic Hypertension in the Elderly Program cohort had no measured negative effects and , for some measures , a slight positive effect on cognitive , physical , and leisure function . The positive findings in favor of the treatment group were small . There was no effect on measures related to emotional state . Measures of cognitive and emotional function were stable in both groups for the duration of the study . Both treatment groups showed a modest trend toward deterioration of some measures of physical and leisure function over the study period . CONCLUSIONS The overall study cohort exhibited decline over time in activities of daily living , particularly the more strenuous ones , and some decline in certain leisure activities . However , mood , cognitive function , basic self-care , and moderate leisure activity were remarkably stable for both the active and the placebo groups throughout the entire study . Results of this study support the inference that medical treatment of isolated systolic hypertension does not cause deterioration in measures of cognition , emotional state , physical function , or leisure activities OBJECTIVE To assess the long-term relationship of midlife blood pressure levels to late-life cognitive function . DESIGN The 4678 surviving cohort members of the prospect i ve Honolulu Heart Program ( baseline , 1965 - 1968 ) were examined a fourth time in 1991 through 1993 and given a cognitive test . PARTICIPANTS The subjects were 3735 Japanese-American men living in Hawaii in the community or in institutions , with an average age of 78 years at the fourth examination . MAIN OUTCOME MEASURES Cognitive function , measured by the 100-point Cognitive Abilities Screening Instrument ( CASI ) , was categorized into good ( reference : a CASI score of 92 to 100 ) , intermediate ( < 92 to 82 ) , and poor ( < 82 ) . Midlife systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) values were measured in 1965 , 1968 , and 1971 . A respondent was classified into the following categories if two of three measurements fell into the following groups : for SBP , < 110 , 110 to 139 , 140 to 159 , and > or = 160 mm Hg ; and for DBP , < 80 , 80 to 89 , 90 to 94 , and > or = 95 mm Hg . RESULTS When we controlled for age and education , the risk for intermediate and poor cognitive function increased progressively with increasing level of midlife SBP category ( P for trend < .03 and < .001 , respectively ) . For every 10-mm Hg increase in SBP there was an increase in risk for intermediate cognitive function of 7 % ( 95 % confidence interval [ CI ] , 3 % to 11 % ) and for poor cognitive function of 9 % ( 95 % CI , 3 % to 16 % ) . Adjustment for prevalent stroke , coronary heart disease , and sub clinical atherosclerosis reduced the strength of the relationship between midlife SBP and poor cognitive function to 5 % ( 95 % CI , 0 % to 12 % ) . The level of cognitive function was not associated with midlife DBP . CONCLUSIONS Midlife SBP is a significant predictor of reduced cognitive function in later life . Early control of SBP levels may reduce the risk for cognitive impairment in old age 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 This study included the introduction of a new , qualitative , self-structured measure of quality of life ( QOL ) after meta- analysis had shown that prestructured quantitative measures yielded insignificant results . This study compared the pre- and post-treatment evaluations of 268 men with mild hypertension , aged 40 to 65 years , who were r and omly allocated to three treatment groups ( methyldopa , isradipine , and placebo ) with that of 155 normotensive subjects . It was found that the study participants defined QOL qualitatively differently from the way it was defined by physicians . Normotensive subjects showed a better QOL status in most prestructured measures whereas the patients taking isradipine showed better results on evaluation of the current level of their self-defined domains . The combined quantitative and qualitative approach to measuring QOL may help to clarify this important aspect of medical research , both conceptually and method ologically BACKGROUND Despite treatment , there is often a higher incidence of cardiovascular complications in patients with hypertension than in normotensive individuals . Inadequate reduction of their blood pressure is a likely cause , but the optimum target blood pressure is not known . The impact of acetylsalicylic acid ( aspirin ) has never been investigated in patients with hypertension . We aim ed to assess the optimum target diastolic blood pressure and the potential benefit of a low dose of acetylsalicylic acid in the treatment of hypertension . METHODS 18790 patients , from 26 countries , aged 50 - 80 years ( mean 61.5 years ) with hypertension and diastolic blood pressure between 100 mm Hg and 115 mm Hg ( mean 105 mm Hg ) were r and omly assigned a target diastolic blood pressure . 6264 patients were allocated to the target pressure < or = 90 mm Hg , 6264 to < or = 85 mm Hg , and 6262 to < or = 80 mm Hg . Felodipine was given as baseline therapy with the addition of other agents , according to a five-step regimen . In addition , 9399 patients were r and omly assigned 75 mg/day acetylsalicylic acid ( Bamycor , Astra ) and 9391 patients were assigned placebo . FINDINGS Diastolic blood pressure was reduced by 20.3 mm Hg , 22.3 mm Hg , and 24.3 mm Hg , in the < or = 90 mm Hg , < or = 85 mm Hg , and < or = 80 mm Hg target groups , respectively . The lowest incidence of major cardiovascular events occurred at a mean achieved diastolic blood pressure of 82.6 mm Hg ; the lowest risk of cardiovascular mortality occurred at 86.5 mm Hg . Further reduction below these blood pressures was safe . In patients with diabetes mellitus there was a 51 % reduction in major cardiovascular events in target group < or = 80 mm Hg compared with target group < or = 90 mm Hg ( p for trend=0.005 ) . Acetylsalicylic acid reduced major cardiovascular events by 15 % ( p=0.03 ) and all myocardial infa rct ion by 36 % ( p=0.002 ) , with no effect on stroke . There were seven fatal bleeds in the acetylsalicylic acid group and eight in the placebo group , and 129 versus 70 non-fatal major bleeds in the two groups , respectively ( p<0.001 ) . INTERPRETATION Intensive lowering of blood pressure in patients with hypertension was associated with a low rate of cardiovascular events . The HOT Study shows the benefits of lowering the diastolic blood pressure down to 82.6 mm Hg . Acetylsalicylic acid significantly reduced major cardiovascular events with the greatest benefit seen in all myocardial infa rct ion . There was no effect on the incidence of stroke or fatal bleeds , but non-fatal major bleeds were twice as common BACKGROUND High blood pressure and stroke are associated with increased risks of dementia and cognitive impairment . This study aim ed to determine whether blood pressure lowering would reduce the risks of dementia and cognitive decline among individuals with cerebrovascular disease . METHODS The Perindopril Protection Against Recurrent Stroke Study ( PROGRESS ) was a r and omized , double-blind , placebo-controlled trial conducted among 6105 people with prior stroke or transient ischemic attack . Participants were assigned to either active treatment ( perindopril for all participants and indapamide for those with neither an indication for nor a contraindication to a diuretic ) or matching placebo(s ) . The primary outcomes for these analyses were dementia ( using DSM-IV criteria ) and cognitive decline ( a decline of 3 or more points in the Mini-Mental State Examination score ) . RESULTS During a mean follow-up of 3.9 years , dementia was documented in 193 ( 6.3 % ) of the 3051 r and omized participants in the actively treated group and 217 ( 7.1 % ) of the 3054 r and omized participants in the placebo group ( relative risk reduction , 12 % [ 95 % confidence interval , -8 % to 28 % ] ; P = .2 ) . Cognitive decline occurred in 9.1 % of the actively treated group and 11.0 % of the placebo group ( risk reduction , 19 % [ 95 % confidence interval , 4 % to 32 % ] ; P = .01 ) . The risks of the composite outcomes of dementia with recurrent stroke and of cognitive decline with recurrent stroke were reduced by 34 % ( 95 % confidence interval , 3 % to 55 % ) ( P = .03 ) and 45 % ( 95 % confidence interval , 21 % to 61 % ) ( P<.001 ) , respectively , with no clear effect on either dementia or cognitive decline in the absence of recurrent stroke . CONCLUSIONS Active treatment was associated with reduced risks of dementia and cognitive decline associated with recurrent stroke . These findings further support the recommendation that blood pressure lowering with perindopril and indapamide therapy be considered for all patients with cerebrovascular disease Abstract Objective : To establish whether initiation of treatment with diuretic or β blocker is associated over 54 months with change in cognitive function . Design : A cognitive sub study , nested within a r and omised , placebo controlled , single blind trial . Setting : 226 general practice s from the Medical Research Council 's general practice research framework . Subjects : A subset of 2584 subjects sequentially recruited from among the 4396 participants aged 65 - 74 in the trial of treatment of hypertension in older adults . The 4396 subjects were r and omised to receive diuretic , β blocker , or placebo . Subjects had mean systolic pressures of 160 - 209 mm Hg and mean diastolic pressures < 115 mm Hg during an eight week run in . Outcome measures : The rate of change in paired associate learning test ( PALT ) and trail making test part A ( TMT ) scores ( administered at entry and at 1 , 9 , 21 , and 54 months ) over time . Results : There was no difference in the mean learning test coefficients ( rate of change of score over time ) between the three treatments : diuretic -0.31 ( 95 % confidence interval -0.23 to -0.39 ) , β blocker -0.33 ( -0.25 to -0.41 ) , placebo -0.30 , ( -0.24 to -0.36 ) . There was also no difference in the mean trail making coefficients ( rate of change in time taken to complete over time ) between the three groups : diuretic -2.73 ( 95 % confidence interval -3.57 to -1.88 ) , β blocker -2.08 ( -3.29 to -0.87 ) , placebo -3.01 , ( -3.69 to -2.32 ) . A less conservative protocol analysis confirmed this negative finding . Conclusion : Treating moderate hypertension in older people is unlikely to influence , for better or for worse , subsequent cognitive function . Key messages Key messages Studies have shown that treating hypertension in older adults reduces cardiovascular mortality and morbidity Treating moderate hypertension with either diuretic or β blocker does not seem to influence cognitive function Concerns about damaging cognition should not deter doctors from treating hypertension in older patients Age should no longer be a factor in the decision to initiate antihypertensive BACKGROUND The apparent shortfall in prevention of coronary heart disease ( CHD ) noted in early hypertension trials has been attributed to disadvantages of the diuretics and beta blockers used . For a given reduction in blood pressure , some suggested that newer agents would confer advantages over diuretics and beta blockers . Our aim , therefore , was to compare the effect on non-fatal myocardial infa rct ion and fatal CHD of combinations of atenolol with a thiazide versus amlodipine with perindopril . METHODS We did a multicentre , prospect i ve , r and omised controlled trial in 19 257 patients with hypertension who were aged 40 - 79 years and had at least three other cardiovascular risk factors . Patients were assigned either amlodipine 5 - 10 mg adding perindopril 4 - 8 mg as required ( amlodipine-based regimen ; n=9639 ) or atenolol 50 - 100 mg adding bendroflumethiazide 1.25 - 2.5 mg and potassium as required ( atenolol-based regimen ; n=9618 ) . Our primary endpoint was non-fatal myocardial infa rct ion ( including silent myocardial infa rct ion ) and fatal CHD . Analysis was by intention to treat . FINDINGS The study was stopped prematurely after 5.5 years ' median follow-up and accumulated in total 106 153 patient-years of observation . Though not significant , compared with the atenolol-based regimen , fewer individuals on the amlodipine-based regimen had a primary endpoint ( 429 vs 474 ; unadjusted HR 0.90 , 95 % CI 0.79 - 1.02 , p=0.1052 ) , fatal and non-fatal stroke ( 327 vs 422 ; 0.77 , 0.66 - 0.89 , p=0.0003 ) , total cardiovascular events and procedures ( 1362 vs 1602 ; 0.84 , 0.78 - 0.90 , p<0.0001 ) , and all-cause mortality ( 738 vs 820 ; 0.89 , 0.81 - 0.99 , p=0.025 ) . The incidence of developing diabetes was less on the amlodipine-based regimen ( 567 vs 799 ; 0.70 , 0.63 - 0.78 , p<0.0001 ) . INTERPRETATION The amlodipine-based regimen prevented more major cardiovascular events and induced less diabetes than the atenolol-based regimen . On the basis of previous trial evidence , these effects might not be entirely explained by better control of blood pressure , and this issue is addressed in the accompanying article . Nevertheless , the results have implication s with respect to optimum combinations of antihypertensive agents Objective To assess clinical outcomes in the Study on COgnition and Prognosis in the Elderly ( SCOPE ) in patients who did not receive add-on antihypertensive therapy after r and omization , i.e. in patients that best reflect the original intention of a placebo-controlled trial . Design Post-hoc analysis of a prospect i ve , r and omized , controlled trial . Setting s and participants Five hundred and twenty-seven centres in 15 countries participated in SCOPE . Patients aged 70–89 years , with systolic blood pressure 160–179 mmHg and /or diastolic blood pressure 90–99 mmHg , and preserved cognitive function were eligible . Out of 4937 patients in SCOPE , 2098 did not receive add-on therapy . Intervention The number of patients who received c and esartan 8–16 mg once daily was 1253 , and 845 received placebo . Mean follow-up was 3.7 and 3.5 years , respectively . Main outcome measures Primary : major cardiovascular events ( cardiovascular mortality , non-fatal stroke or non-fatal myocardial infa rct ion ) . Secondary : total mortality , cardiovascular mortality , fatal and non-fatal myocardial infa rct ion , fatal and non-fatal stroke , cognitive function , and dementia . Results The treatment groups were generally well balanced for baseline characteristics . Blood pressure fell by 21.8/11.0 mmHg in the c and esartan group and by 17.2/8.4 mmHg in the placebo group . There were significant relative risk reductions with c and esartan in major cardiovascular events ( 32 % , P = 0.013 ) , cardiovascular mortality ( 29 % , P = 0.049 ) , and total mortality ( 27 % , P = 0.018 ) . There were no significant differences between the treatment groups in cognitive outcomes . Both treatments were generally well tolerated . Conclusions Treatment of elderly patients with mild hypertension is beneficial and supports current recommendations . C and esartan appears an appropriate therapy in such patients , in view of its favourable tolerability profile and ability to reduce major cardiovascular events OBJECTIVE To determine the association between medications that ameliorate vascular risk factors and the prevalence of cognitive impairment and dementia in an older African-American population . DESIGN A community-based survey to identify subjects with and without evidence of cognitive impairment and subsequent diagnostic evaluation of a stratified sample of these subjects using formal diagnostic criteria for dementia and Alzheimer 's disease ( AD ) . SETTING Urban neighborhoods in Indianapolis , Indiana . SUBJECTS A r and om sample of 2,212 African-American adults aged 65 years and older residing in 29 contiguous census tracts . MEASUREMENTS Subjects ' scores on the Community Screening Instrument for Dementia ( CSID ) , formal diagnostic and clinical assessment s for dementia , current medication use and history of medical illnesses , both self-report and , where possible , from an informant . Four outcome measures were defined by the following criteria : ( 1 ) cognitive impairment as defined by the subject 's performance on the CSID cognitive scale ; ( 2 ) cognitive/ functional impairment as defined by the total CSID score that included a relative 's assessment of the subject 's functional abilities ; ( 3 ) dementia as defined by explicit diagnostic criteria ; and ( 4 ) possible or probable Alzheimer 's Disease as defined by explicit criteria . RESULTS The vascular risk factor mediating medications , when analyzed together , were associated with a significantly decreased risk of diagnosis of cognitive impairment after controlling for age , education , and stroke ( OR 0.73 , P = .01 ) and also a significantly decreased risk of cognitive/functional impairment ( OR 0.66 , P = .02 ) . Antihypertensive agents , excluding central ly acting sympatholytic drugs were associated with a significantly reduced risk of diagnosis of cognitive impairment ( OR 0.56 , P < .01 ) and cognitive/functional impairment ( OR 0.64 , P = .01 ) . Central ly acting sympatholytic agents were associated with an increased risk of diagnosis of cognitive impairment ( OR 2.24 , P < .01 ) . There was a trend toward protection from a diagnosis of AD and dementia for the vascular risk factor mediating medications and for the antihypertensive medication , but this did not reach significant levels . CONCLUSIONS These data suggest that the use of medications to ameliorate vascular risk factors , particularly antihypertensive medication , may also be useful in reducing the risk of cognitive impairment in older subjects . However , they also suggest that physicians should be cautious in prescribing antihypertensive drugs with central ly acting sympatholytic properties to older subjects This study aims to describe factors associated with cognitive decline among 2584 subjects , aged 65 - 74 , who were followed up for 54 months in the Medical Research Council Elderly Hypertension Trial ( 1982 - 1989 ) . The subjects completed a cognitive test , the Paired Associate Learning Test ( PALT ) , five times over this period . Decline on the PALT was associated with advanced age , male sex , rural residence , depression and low intelligence . These effects were modified by gender and level of pre-morbid intelligence . Advanced age , rural residence and number of cigarettes smoked daily were only associated with PALT decline among women of below median intelligence . The association between depression and PALT decline was only apparent in women of below median intelligence and men of above median intelligence . While these findings are consistent with other research into cognitive decline , they differ in some ways from reported risk factors for dementia , suggesting aetiological separateness . That women were more vulnerable than men to the effects of age and smoking raises the question of the impact on cognition of accelerated atherosclerosis after the menopause In the Systolic Hypertension in the Elderly Program ( SHEP ) trial ( 1985 - 1990 ) , active treatment reduced the incidence of cardiovascular events , but not that of dementia and disability , as compared with placebo . This study aims to evaluate if assessment of cognitive and functional outcomes was biased by differential dropout . Characteristics of subjects who did or did not participate in follow-up cognitive and functional evaluations were compared . The relative risks of incident cognitive impairment and disability were assessed in the two treatment groups , with the use of the reported findings and under the assumption that the proportions of cognitive and functional impairment among dropouts increased . Assignment to the placebo group and the occurrence of cardiovascular events independently predicted missed assessment s. From the reported findings , the risk of cognitive and functional impairment was similar between the two treatment groups . However , when 20 - 30 % and 40 - 80 % of the subjects who missed the assessment were assumed to be cognitively and , respectively , functionally impaired , assignment to active treatment reduced the risk of these outcomes . In the SHEP , the cognitive and functional evaluations were biased toward the null effect by differential dropout . This might have obscured the appraisal of a protective effect of treatment on the cognitive and functional decline of older hypertensive adults Background Isolated systolic hyprtension occurs in around 8 % of Chinese people aged 60 years or older . In 1988 , the Systolic Hypertension in China ( Syst-China ) Collaborative Group started to investigate whether active treatment could reduce the incidence of stroke and other cardiovascular complications in older patients with isolated systolic hypertension . Methods All patients were initially started on masked placebo . After stratification for centre , sex and previous cardiovascular complications , alternate patients ( n = 1253 ) were assigned nitrendipine at 10–40 mg daily , with the addition of captopril at 12.5–50.0 mg daily or hydrochlorothiazide at 12.5–50.0 mg daily , or both , if a sufficient blood pressure fall was not obtained . In the remaining 1141 control patients , matching placebos were administered similarly . Results At entry , sitting blood pressure averaged 170.5 mmHg systolic and 86.0 mmHg diastolic , age averaged 66.5 years and total serum cholesterol was 5.1 mmol/l . After 2 years of follow-up , sitting systolic and diastolic blood pressures had fallen by 10.9 mmHg and 1.9 mmHg in the placebo group and by 20.0 mmHg and 5.0 mmHg in the active treatment group . The intergroup differences were 9.1 mmHg systolic ( 95 % confidence interval 7.6–10.7 mmHg ) and 3.2 mmHg diastolic ( 95 % confidence interval 2.4–4.0 ) . Active treatment reduced total strokes by 38 % ( from 20.8 to 13.0 endpoints per 1000 patient-years , P = 0.01 ) , all-cause mortality by 39 % ( from 28.4 to 17.4 endpoints per 1000 patient-years , P = 0.003 ) , cardiovascular mortality by 39 % ( from 15.2 to 9.4 endpoints per 1000 patient-years , P = 0.03 ) , stroke mortality by 58 % ( from 6.9 to 2.9 endpoints per 1000 patient-years , P = 0.02 ) , and all fatal and nonfatal cardiovascular endpoints by 37 % ( from 33.3 to 21.4 endpoints per 1000 patient-years , P = 0.004 ) . Conclusions Antihypertensive treatment prevents stroke and other cardiovascular complications in older Chinese patients with isolated systolic hypertension . Treatment of 1000 Chinese patients for 5 years could prevent 55 deaths , 39 strokes or 59 major cardiovascular endpoints OBJECTIVES Hypertension is associated with impaired cognition , but it is unclear whether this impairment is reversible . We sought to evaluate the effect of blood pressure reduction on cognition . DESIGN A r and omized , double-blind trial . SETTING A single center , with assessment s in subjects ' domiciles . PARTICIPANTS Community-screened subjects more than 69 years of age who had median diastolic pressures > 99 mm Hg and systolic pressures > 159 mm Hg or diastolic > 85 mm Hg and systolic > 179 mm Hg with Mini-Mental State Examination scores of 20 to 28 . Subjects had not previously received antihypertensive treatment . INTERVENTION Captopril 12.5 mg twice daily or bendrofluazide 2.5 mg daily for 24 weeks , preceded by a 2-week placebo phase . MEASUREMENTS Cognition was evaluated by a psychometric test battery comprising Immediate and Delayed Logical Memory , Paired Associates recall , Raven 's Progressive Matrices , Halstead Reitan Trail Making A , and the Anomalous Sentences Repetition Test . RESULTS Eighty-one subjects ( 28 male , 53 female ) were treated ( 41 captopril , 40 bendrofluazide ) . At entry , mean age was 76.1 years ( range 70 - 84 ) , mean blood pressure was 191 ( 160 - 230 ) mm Hg systolic , 101 ( 88 - 110 ) mm Hg diastolic , and mean MMSE score 26.1 . A total of 69 subjects completed the trial . The 25th , 50th , and 75th percentiles of the difference between pretreatment and Week 24 blood pressures wer 15 mm Hg , 35 mm Hg , and 50 mm Hg ( systolic ) and 5 mm Hg , 10 mm Hg , and 19 mm Hg ( diastolic ) . There were no significant differences in any psychometric test between captopril and bendrofluazide . The 19 subjects in the quartile that lowered their diastolic blood pressure most ( > or = 19 mm Hg ) had improved scores on Anomalous Sentences ( P = .012 ) and Paired Associates ( P = .044 ) compared to the 19 subjects in the least blood pressure responsive quartile ( fall < or = 5 mm Hg)s . CONCLUSION The treatment of hypertension is not hazardous to cognitive function in older people with pre-existing cognitive impairment . Long-term adequate blood pressure control may reverse cognitive impairment associated with pre-existing hypertension |
1,247 | 30,524,374 | The prevalence increased with goiter size and with the extent of substernal extension .
Esophageal physiology changes : Goiter patients had increased esophageal transit time , positively correlated with goiter size , but unrelated to esophageal motility disturbances .
Decrease in the upper esophageal sphincter pressure occurred early after surgery , and normalized within 6 months .
Swallowing related patient-reported outcomes : Evaluated by vali date d question naires , swallowing symptoms worsened in the early period after thyroidectomy , but improved after 6 months , as compared to baseline .
Conclusions : Thyroidectomy relieved patients with goiter from dysphagia , within 6 months of surgery probably via increase in the cross-sectional area of the esophagus . | Background : Patients with goiter referred for thyroidectomy report swallowing difficulties .
This might be associated with esophageal compression and deviation as this is present in a significant number of patients .
Studies on how goiter and subsequently its treatment affect the esophagus are sparse and point in various directions .
Our aim was to investigate , through a systematic review , the impact of goiter and thyroidectomy on esophageal anatomy , esophageal physiology , and subjective swallowing dysfunction . | Importance It is important that clinicians underst and consequences of thyoridectomy on swallowing from the patient perspective to better care for this population . Objective Using rigorous qualitative methodology , this study set out to characterize the effect of swallowing-related symptoms after thyroidectomy on patient quality of life and swallowing-related outcomes . Design , Setting , and Participants Prospect i ve , grounded theory analysis of interviews with 26 patients at 3 time points after thyroidectomy ( 2 weeks , 6 weeks , and 6 months ) . Data were collected from an ongoing clinical trial ( NCT02138214 ) , and outpatient interviews were conducted at the University of Wisconsin Hospital and Clinics . All participants were age 21 to 73 years with a diagnosis of papillary thyroid cancer without cervical or distant metastases and had undergone total thyroidectomy . Exclusion criteria were preexisting vocal fold abnormalities ( eg , polyps , nodules ) , neurological conditions affecting the voice or swallowing ability , and /or development of new-onset vocal fold paresis or paralysis ( lasting longer than 6 months ) after total thyroidectomy . Interventions Total thyroidectomy . Main Outcomes and Measures Symptoms of dysphagia and related effects on quality of life elicited through grounded theory analysis of semistructured interviews with patients after thyroidectomy design ed to foster an open-ended , patient-driven discussion . Results Of the 26 patients included , 69 % were women ( n = 18 ) ; mean ( SD ) age , 46.4 ( 14.1 ) years ; mean ( SD ) tumor diameter 2.2 ( 1.4 ) cm . Two weeks after thyroidectomy , 80 % of participants ( n = 20 ) reported at least 1 swallowing-related symptom when prompted by the interview cards ; during the open interview , 53 % of participants ( n = 14 ) volunteered discussion of swallowing-related symptoms unprompted . However , only 8 % of participants in this study ( n = 2 ) qualified for a follow-up dysphagia evaluation , indicating that the majority of reported symptoms were subjective in nature . Six weeks and 6 months after thyroidectomy , 42 % ( n = 11 ) and 17 % ( n = 4 ) of participants , respectively , reported continued swallowing symptoms using the prompts ; 12 % ( n = 3 ) discussed symptoms without prompting cards at both time points . Conclusions and Relevance Swallowing symptoms after thyroidectomy are underreported in the literature . This study revealed that as many as 80 % of patients who have thyroidectomy may experience swallowing-related symptoms after surgery , and many develop compensatory strategies to manage or reduce the burden of these symptoms . Considering the large number of individuals who may experience subjective dysphagia , preoperative counseling should include education and management of such symptoms HYPOTHESES Goiter is a surgically reversible cause of positional dyspnea ( PD ) . Substernal tracheal compression ( TC ) predicts PD relief after thyroidectomy ( Tx ) . DESIGN Retrospective analysis of a prospect i ve structured management algorithm . SETTING Endocrine surgery academic center . METHODS Before Tx , 1081 patients were queried about PD . Those patients with substernal goiter underwent computed tomography , and their degree of TC was estimated as greatest percent reduction of transverse tracheal diameter . For 197 patients with PD , TC , or both , surgical outcomes were examined with a mean follow- up of 12.6 months . After Tx , patients who carried the diagnosis of obstructive sleep apnea were referred for repeat sleep study evaluation . RESULTS Positional dyspnea was reported by 188 of 1081 patients , and after Tx the PD improved or resolved in 82.4 % . In the 151 patients with substernal goiter , TC was present on imaging in 97.2 % ; the mean ( range ) TC was 34 % ( 5%-90 % ) . Patients with TC had a high likelihood of PD ( 93.5 % ) . After substernal goiter resection , PD improved in stepwise association with total resected thyroid gl and weight . Improvement in PD was strongly predicted by both gl and weight of 100 g or more ( P.001 ) and by TC of 35 % or more ( P.01 ) . After Tx , 59 of 77 snorers ( 76.6 % ) reported improvement in snoring , 77.1 % of patients with obstructive sleep apnea reported improved PD , and 2 of 3 retested patients with obstructive sleep apnea demonstrated objective improvement in sleep study apnea-hypopnea index . CONCLUSIONS Resection of bulky goiter frequently improves PD , which in substernal goiter is highly associated with TC . Either PD or TC of 35 % or more prompt Tx . Goiter should be considered when obstructive sleep apnea is diagnosed Background Voice and swallowing alterations are common complaints after thyroidectomy , even in the absence of laryngeal nerve impairment . However , voice and swallowing functions after robotic thyroidectomy have not been thoroughly investigated . This study compared the functional outcomes for voice and swallowing after robotic thyroidectomy and conventional open thyroidectomy . Methods The study prospect ively analyzed the voice and swallowing functions of patients with thyroid nodules who underwent robotic thyroidectomy by a gasless unilateral axillo-breast ( GUAB ) approach ( 50 cases ) or by conventional open thyroidectomy ( 61 cases ) from September 2009 to October 2010 . Videolaryngostroboscopy or flexible laryngoscopy was performed pre- and postoperatively . Subjective voice and swallowing alterations were assessed by question naire preoperatively and then 1 day , 1 week , 1 month , 3 months , and 6 months postoperatively . In addition , objective acoustic voice analysis was performed using a Multidimensional Voice Program , with Voice Range Profiles and maximum phonation times measured preoperatively and then 1 week , 1 month , 3 months , and 6 months postoperatively . Results Subjective postoperative voice function was significantly better in the robotic group at 1 day , 1 month , and 3 months postoperatively than in the open group . The mean values of fundamental frequency , jitter , shimmer and noise-to-harmonic ratio before and after surgery did not differ between the two groups . However , the frequency range and the highest frequency were significantly better in the robotic group than in the open group at 3 months postoperatively . Subjective swallowing function did not differ between the two groups . Conclusion Postoperative voice function is better with robotic thyroidectomy using the GUAB approach than with conventional open thyroidectomy . This is an advantage of robotic thyroidectomy by the GUAB approach in addition to the excellent cosmesis ObjectiveS wallowing disorders are frequent complaints after thyroidectomy even in the absence of recurrent laryngeal nerve palsy . The aim of this study was to assess different symptoms in relation to laryngeal mobility following thyroidectomy . Material s and methods 53 patients ( mean age 52.4 ± 12.5 years ; 36 female ) with initially benign diagnosis and intact recurrent nerve functioning were prospect ively evaluated . Laryngeal movement was analyzed by ultrasound preoperatively and 1 , 3 , and 6 months postoperatively . In addition , a dysphagia and voice-specific quality -of-life question naire was used . Results Mean laryngeal movement differed between genders preoperatively and postoperatively result ing in a recovery predominantly in women ( reduction of mobility at 1 , 3 , and 6 months postoperatively in females was 6.0 , 3.7 , and 1.5 mm , and in males 13.8 , 11.7 , and 10.3 mm , respectively ) . Mainly , women reported hoarseness ( 9 females ) and cervical discomfort ( 7 females , 3 males ) 1 month postoperatively . After 6 months , these complaints resolved ( cervical discomfort 1 female ) . Conclusion Laryngeal mobility was significantly impaired postoperatively and only females revealed a recovery close to baseline after 6 months . Although showing only a small grade of recovery of laryngeal movement , subjective clinical symptoms were found to be rare in male patients BACKGROUND We performed a prospect i ve analysis on voice and swallowing alterations following total thyroidectomy ( TT ) , in the absence of recurrent nerve injury . METHODS Patients aged 21 to 65 years undergoing TT , in the absence of laryngeal/pulmonary disease , previous neck surgery , or malignant diseases , were subjected to videostrobolaryngoscopy ( VSL ) , acoustic voice analysis ( AVA ) , and maximum phonation time ( MPT ) tests preoperatively and 3 months postoperatively . Voice impairment scores ( VIS ) and swallowing impairment scores ( SIS ) were obtained preoperatively , and at 1 week , 1 month , and 3 months postoperatively . RESULTS Among the 127 selected patients , 39 completed the postoperative evaluation . No recurrent nerve injury was observed during the postoperative VSL in any of the patients . Preoperative and postoperative AVA and MPT scores did not differ significantly . The mean postoperative VIS was significantly higher than the preoperative VIS at 1 week and 1 month after TT ( 13.7 and 9.6 vs 4.4 , respectively ; P < .05 ) but not 3 months after TT ( 6.7 ) . The mean SIS was higher than the preoperative SIS at 1 week , 1 month , and 3 months after TT ( 10.3 , 6.0 , and 2.8 vs 0.5 , respectively ; P < .05 ) . CONCLUSIONS Physicians should inform patients that transient voice and swallowing symptoms may occur following total thyroidectomy , and our data suggest mild symptoms may occur in the majority of operated patients BACKGROUND Patients undergoing thyroidectomy often complain aerodigestive disorders . In a previous study we showed the associations between voice impairment and proximal acid reflux , swallowing impairment and Upper Esophageal Sphyncter ( UES ) incoordination and the decrease in UES pressure in thirty-six patients observed before and soon afterwards uncomplicated thyroidectomy . This study investigated the state of post-thyroidectomy esophageal motility changes and its associations with these disorders after 18 - 24 months . PATIENTS AND METHODS The thirty-six patients prospect ively recruited according to selection criteria ( thyroid volume ≤60 ml , benign disease , age 18 - 65 years , previous neck surgery , thyroiditis , pre- or postoperative vocal cord palsy ) underwent voice ( VIS ) and swallowing ( SIS ) impairment scores , esophageal manometry and pH monitoring once again . RESULTS After 18 - 24 months , both VIS and SIS recovered ( respectively : p=0,022 ; p=0,0001 ) ; UES pressure increased ( p=0,0001 ) nearing the preoperative values . The persistence of swallowing complaints were associated with the persistence of esophageal incoordination ( p=0,03 ) ; the association between voice impairment and proximal acid reflux was confirmed ( p<0,001 ) . CONCLUSIONS Our study confirms that aerodigestive disorders after uncomplicated thyroidectomy , largely transient , are strictly connected with upper esophageal motility changes . In this viewpoint , the innervation of upper aerodigestive anatomical structures ( larynx , pharynx , upper esophagus ) and its variations should be focused Objective Swallowing and voice impairment are common after thyroidectomy . We evaluated short-term functional changes in esophageal motility in a series of patients who had undergone total thyroidectomy . Several studies have investigated these symptoms by means of interviews or question naires . Study Design Prospect i ve study . Setting Academic research . Material s and Methods Thirty-six consenting patients were prospect ively recruited . Eligibility criteria were thyroid volume ≤60 mL , benign disease , and age between 18 and 65 years . Exclusion criteria were previous neck surgery , severe thyroiditis , hyperthyroidism , and pre- or postoperative vocal cord palsy . Voice impairment score , swallowing impairment score , lower esophageal sphincter pressure , esophageal motility , upper esophageal pressure , and coordination were evaluated preoperatively and 30 to 45 days after surgery . Results Postoperative swallowing impairment ( appearance or worsening of dysphagia ) was found in 20 % of patients and voice impairment in more than 30 % . Both preoperative and postoperative esophageal motility were similar . All patients showed an average decrease of 25 % in upper esophageal pressure , although the pressure was within normal range . Swallowing alterations were associated with upper esophageal incoordination ( P < .03 ) , and proximal acid reflux was significantly associated with voice impairment ( P < .02 ) . Conclusion After uncomplicated thyroidectomy , decreased upper esophageal pressure may explain both pharyngeal ( dysphagia ) and laryngeal ( vocal impairment ) exposure to acid . In the future , proton pump inhibitor therapy protocol s should be evaluated A globus sensation is one of the most common complaints in otolaryngologic clinics , and laryngopharyngeal reflux is the most common cause . However , thyroid nodules also can cause globus symptoms . The purpose of this study was to identify the characteristics of thyroid nodules that cause globus . We selected patients prospect ively with a single thyroid nodule on ultrasonograms . Patients with other causes of globus symptoms were excluded using question naires , fiber optic laryngoscopic examinations , and a psychiatric screening tool . In total , 175 patients were enrolled . Patients were divided into two groups according to globus symptoms . Ultrasonographic characteristics and clinicopathological parameters were compared between the groups . Among various clinicopathologic and ultrasonographic parameters , size and horizontal location of the thyroid nodule showed significant differences between the groups . Nodules larger than 3 cm and those located anterior to the trachea had a tendency to cause globus symptoms . Regarding horizontal location , nodules that all parts were located anterior to the trachea showed a higher tendency to cause globus symptoms than nodules that only some parts were located anterior to the trachea . In conclusion , thyroid nodules with specific size and location can cause globus symptoms , and this finding can be indicated in patient counseling . Also , conservative treatments or thyroidectomy may be helpful in relieving patients ’ globus symptoms Background In conventional open thyroidectomy , it is necessary to create a sub-platysma muscle flap in front of the strap muscle to provide working space . Adhesion between the flap and the strap muscle can occur after the operation , disrupting strap muscle movement and causing a swallowing disorder . Gasless transaxillary endoscopic thyroidectomy approaches the thyroid through the posterior of the strap muscle and does not require a sub-platysma muscle flap . The present study compared flap/muscle adhesion and occurrence of swallowing disorder following gasless transaxillary endoscopic thyroidectomy versus conventional open thyroidectomy . Methods Patients ( N = 47 ) receiving thyroidectomy at the Kangbuk Samsung Medical Center , Seoul , Korea , were divided into two groups : group O ( 24 patients ) underwent conventional open thyroidectomy , and group E ( 23 patients ) underwent gasless transaxillary endoscopic thyroidectomy . The subjective Swallowing Impairment Index (SIS)-6 was used to evaluate the degree of post-operative swallowing disorder . Video recordings of swallowing movement were used to determine the contraction/relaxation ( CR ) ratio and evaluate adhesion , pre-operation , 3 days post-operation , and 1 month post-operation . Barium videofluoroscopy was used to measure movement of the hyoid bone and strap muscle . Results Group O had significantly higher post-operative SIS-6 scores than group E ( p < 0.027 ) , indicating greater swallowing disorder . The CR ratio increased in group O after the operation and continued to increase during 1 month post-operation , but decreased in group E ( p < 0.001 ) . Videofluoroscopy showed that hyoid bone movement in group O decreased by 55.46 and 56.75 % at 3 days and 1 month post-operation , respectively , while the corresponding decreases in group E were 84.04 and 83.69 % . Conclusions Conventional open thyroidectomy allowed adhesion of the strap muscle and sub-platysma muscle flap , result ing in non-specific dysphagia . These complications did not occur following gasless transaxillary endoscopic thyroidectomy Background Swallowing-related quality of life ( QoL ) in patients with benign thyroid goiters is not much studied . The aim of this study was to assess swallowing function impairment in patients with benign goiters , compare it to a control population , and also find the impact of thyroidectomy and various factors on the outcome of swallowing function . Methods We performed a prospect i ve case – control study from September 2009 to September 2011 which consisted of 124 patients who were to undergo primary thyroid surgery and 100 age- and sex-matched controls . A translated and vali date d modified swallowing quality -of-life ( SWAL-QOL ) question naire was used to assess patients ’ perception of dysphagia . Presurgery scores of patients and controls and pre- and postsurgery scores ( > 6 months after surgery ) of patients were compared . Results The mean age of males and females in the control and patient groups were 37.7 vs. 39.5 years and 37.4 vs. 39.8 years , respectively . Twelve patients ( 9.7 % ) complained of dysphasia at presentation . Sixty-three patients ( 50.8 % ) underwent total thyroidectomy and 61 ( 49.2 % ) had hemithyroidectomy at the time of initial evaluation , 75 , 23.4 , and 1.6 % of patients were euthyroid , hyperthyroid , and hypothyroid , respectively . Presurgery scores of patients in all of the 11 domains of the SWAL-QOL were lower compared to those of controls . Comparing separately with the matched controls , females had significant differences in nine domains ( except for sleep and fatigue ) of the SWAL-QOL question naire but males did not . Postoperatively , both male and female patients showed significant improvement in the scores of all the domains . Female gender , hyperthyroidism , thyroid nodularity , retrosternal extension , procedure , and weight of the resected specimen were the factors associated with significant improvement in various domains . Conclusion Dysphagia seems to be an underestimated problem in patients with benign goiters . Uncomplicated thyroidectomy results in significant improvement in swallowing-related QoL irrespective of patient profile and extent of thyroidectomy CONTEXT Recurrence rate , after aspiration , in cystic thyroid nodules is very high . Interstitial laser photocoagulation ( ILP ) is a minimally invasive procedure that reduces the need for surgery in patients with a benign solid thyroid nodule . OBJECTIVE The aim of the study was to evaluate the efficacy of ILP on remission rates in recurrent , predominantly cystic thyroid nodules . DESIGN AND METHODS Forty-four consecutive out patients with a symptomatic , recurrent , and cytologically benign cystic ( cyst volume ≥ 2 mL ) thyroid nodule were r and omized to a single aspiration with ( n = 22 ) or without ( n = 22 ) subsequent ILP and followed up after 1 , 3 , and 6 months . RESULTS Successful outcome ( cyst volume ≤ 1 mL ) was obtained in 15 of 22 ( 68 % ) patients in the ILP group , compared to 4 of 22 ( 18 % ) in the aspiration group ( P = .002 ) . In the ILP group , the solid part of the nodule was reduced from a median of 1.8 to 1.0 mL ( P = .02 ) . In the aspiration-alone group , neither the cyst volume nor the solid nodule volume was significantly reduced . The reduction in median visual analog score ( 0 - 10 cm ) for pressure symptoms was significantly higher in the ILP group ( from 3.0 to 0.0 cm ) than in the aspiration-alone group ( from 4.0 to 3.5 cm ) ( P = .006 , between groups ) . No major side effects occurred , and thyroid function was unaffected throughout . CONCLUSIONS US-guided aspiration and subsequent ILP of benign recurrent predominantly cystic thyroid nodules is safe . It significantly reduces recurrence rate , the volume of the solid nodule component , and pressure symptoms . ILP constitutes an important alternative to surgery in such patients Background Voice and swallowing symptoms are frequently reported after thyroidectomy even in absence of objective voice alterations . We evaluated the influence of the video-assisted approach on voice and swallowing outcome of thyroidectomy . Methods Sixty-five patients undergoing total thyroidectomy ( TT ) were recruited . Eligibility criteria were : nodule size ≤30 mm , thyroid volume ≤30 ml , no previous neck surgery . Exclusion criteria were : younger than aged 18 years and older than aged 75 years , vocal fold paralysis , history of voice , laryngeal or pulmonary diseases , malignancy other than papillary thyroid carcinoma . Patients were r and omized for video-assisted ( VAT ) or conventional ( CT ) thyroidectomy . Videostrobolaryngoscopy ( VSL ) , acoustic voice analysis ( AVA ) , and maximum phonation time ( MPT ) evaluation were performed preoperatively and 3 months after TT . Subjective evaluation of voice ( voice impairment score = VIS ) and swallowing ( swallowing impairment score = SIS ) were obtained preoperatively , 1 week , 1 month , and 3 months after TT . Results Fifty-three patients completed the postoperative evaluation : 29 in the VAT group , and 24 in the CT group . No laryngeal nerves injury was shown at postoperative VSL . Mean postoperative MPT , F0 , Flow , Fhigh , and the number of semitones were significantly reduced in the CT group but not in the VAT group . Mean VIS 3 months after surgery was significantly higher than preoperatively in CT group but not in the VAT group . Mean SIS was significantly decreased 1 and 3 months after VAT but not after CT . Conclusions The incidence and the severity of early voice and swallowing postthyroidectomy symptoms are significantly reduced in patients who undergo VAT compared with conventional surgery Background Patients with thyroid disease frequently complain of dysphagia . To date , there have been no prospect i ve studies evaluating swallowing function before and after thyroid surgery . We used the swallowing quality of life ( SWAL-QOL ) vali date d outcomes assessment tool to measure changes in swallowing-related QOL in patients undergoing thyroid surgery . Methods Patients undergoing thyroid surgery from May 2002 to December 2004 completed the SWAL-QOL question naire before and one year after surgery . Data were collected on demographic and clinicopathologic variables , and comparisons were made to determine the effect of surgery on patients ’ perceptions of swallowing function . Results Of 146 eligible patients , 116 ( 79 % ) completed the study . The mean patient age was 49 years , and 81 % were female . Sixty-four patients ( 55 % ) underwent total thyroidectomy and the remainder received thyroid lobectomy . Thirty patients ( 26 % ) had thyroid cancer . The most frequent benign thyroid conditions were multinodular goiter ( 28 % ) and Hashimoto ’s thyroiditis ( 27 % ) . Mean preoperative SWAL-QOL scores were below 90 for nine of the eleven domains , indicating the perception of impaired swallowing and imperfect QOL . After surgery , significant improvements were seen in eight SWAL-QOL domains . Recurrent laryngeal nerve injury was associated with dramatic score decreases in multiple domains . Conclusions In patients with thyroid disease , uncomplicated thyroidectomy leads to significant improvements in many aspects of patient-reported swallowing-related QOL measured by the SWAL-QOL instrument INTRODUCTION The globus sensation is a constant feeling of a lump in the throat and may be associated with thyroid enlargement . A two year prospect i ve study was set up to ascertain the relationship between thyroid pathology and globus symptoms . MATERIAL S AND METHODS All patients undergoing thyroid surgery over a two year period were included . Patients were question ed pre- and post-operatively . Globus symptom scores were recorded using a visual analogue scale . The size , weight and histological features of the removed specimens were correlated and statistical analysis performed . RESULTS Two hundred patients were included in the study ; 58 were symptomatic for globus pharyngeus pre-operatively , and 80 per cent of these patients ' symptoms resolved post-operatively ( p < or = 0.0001 ) . Patients with histological features of inflammation showed the greatest improvement ( p < or = 0.0001 ) . CONCLUSION As many as one-third of patients with a thyroid mass will complain of a globus-like symptom . Patients undergoing thyroid surgery , who are symptomatic for globus pharyngeus , can expect that their symptoms will improve following surgery Local symptoms in the neck such as swallowing and voice disorders , and throat discomfort might be related to a goiter if present , but are also reported by patients suffering from reflux laryngopharyngitis . The aim of our study was to investigate the presence of reflux laryngopharyngitis in patients with nodular goiter before and after uncomplicated total thyroidectomy ( TT ) using a prospect i ve study in University Hospital setting . We considered 25 patients , affected by non-toxic nodular goiter and c and i date s for TT , who complained of local symptoms in the neck . All the patients were carefully interviewed , with emphasis on swallowing and voice disorders , throat discomfort and reflux-related symptoms and underwent a videolaryngoscopy ( VLS ) and a videofluoroscopic swallowing study ( VFSS ) before and 3 months after TT . Before thyroidectomy , reflux laryngopharyngitis-related alterations were present in 68 and 50 % at VLS and VFSS , respectively . After thyroidectomy , the swallowing and voice disorders persisted in 79 and 75 % , respectively , while throat discomfort persisted in 91 % . The results show that patients with a non-toxic nodular goiter who complain of local neck symptoms , before surgery it is appropriate to see if a reflux laryngopharyngitis is present ; VLS and VFSS could be indicated for this and if necessary an antireflux treatment should be administered Purpose A quality of life ( QoL ) assessment is considered an important outcome measure in the treatment of benign thyroid diseases . The aims of this study were to analyze the impact of different surgical treatments on QoL in patients with benign thyroid diseases and to evaluate factors correlating with the QoL outcomes . Methods A prospect i ve longitudinal study was conducted . One hundred thirty-two patients met the inclusion /exclusion criteria and completed the disease-specific question naire , thyroid patient-reported outcome ( ThyPRO ) , before surgery and after 6 months . Preoperative and postoperative QoL outcomes were compared and correlating factors were analyzed . Results Indication for surgery was euthyroid goiter , toxic goiter , and suspicious malignant thyroid disease in 58.3 , 29.5 , and 12.1 % of the patients , respectively . None of the patients had overtly toxic goiter . There were 65.2 % of the patients who underwent total thyroidectomy , while 34.8 % underwent hemithyroidectomy . The total postoperative complication rate was 5.3 % . QoL improved significantly after surgical treatment , independent of the extent of performed surgery . The most affected domain , pre- and postoperative , was for tiredness . QoL improvement was significant for women in all domains , while for men , it was significant in only three domains ( goiter symptoms , emotional susceptibility , and cosmetic complaints ) and in overall QoL. Younger patients had significantly better cognitive functioning and daily life , while elderly patients had significantly less cosmetic complaints . The factors that significantly correlated with improvement of QoL in different domains were lower education level , duration of disease , and microcarcinoma at final histology . Conclusion QoL in patients with benign thyroid diseases improves significantly after operative treatment , independent of the extent of the operation Post-thyroidectomy patients often complain of globus pharyngeus type symptoms . One of the organic pathologies recognized as causing globus pattern symptoms is goitre . We conducted a prospect i ve question naire-based study in the thyroid clinic at Hull Royal Infirmary to examine the relationship between goitre , thyroidectomy and globus pattern symptoms by using the Glasgow-Edinburgh Throat Scale . A question naire-based study in which 41 consecutive patients due to undergo thyroidectomy prospect ively completed the question naire pre-operatively and 12 months post-operatively . A subset of 25 r and omly selected patients also completed the question naire three months post-operatively . Globus symptoms were not worsened by thyroidectomy at three or 12 months . Indeed two of the question ed parameters were significantly improved at three months , and six at one year ( p < 0.023 ) . In conclusion , thyroidectomy does not exacerbate globus pharyngeus symptoms . Indeed , in the absence of other clinical causes , when a patient has a World Health Organization ( WHO ) 2 goitre or greater , thyroidectomy may improve them |
1,248 | 31,278,474 | Based on efficacy and safety , there was a tendency that fruquintinib was superior to regorafenib , as a whole , regorafenib and fruquintinib demonstrated similar clinical benefit for patients with refractory mCRC .
It seems that fruquintinib has less toxic in all- grade toxicity when compared with regorafenib | The optimal treatment in the third-line and later-line setting for metastatic colorectal cancer ( mCRC ) has not been established .
As reported , regorafenib and fruquintinib have shown to be superior to placebo in mCRC .
However , no direct clinical comparison of regorafenib and fruquintinib has been conducted ; we performed a systematic review and network meta- analysis to compare the efficacy and safety of regorafenib and fruquintinib . | Purpose Fruquintinib ( HMPL-013 ) is a novel oral small molecule compound that selectively inhibits vascular endothelial growth factor receptors-1 , -2 , and -3 with potent inhibitory effects on multiple human tumor xenografts . This first-in-human study was conducted to assess the maximum tolerated dose and dose-limiting toxicities , safety and tolerability , pharmacokinetics , and preliminary anti-tumor activity of fruquintinib . Methods Patients 18–70 years old with advanced solid tumors refractory to st and ard therapies were recruited . Fruquintinib was administered orally in 4-week repeating cycles in two regimens , either once daily continuously or once daily for 3-week on/1-week off , until discontinuation due to toxicity or tumor progression . Adverse events were assessed using National Cancer Institute Common Terminology Criteria for Adverse Events v4.0.3 . Pharmacokinetic parameters were measured after a single dose and in multiple dosing . Tumor response was assessed by Response Evaluation Criteria in Solid Tumors v1.0 . Results Forty patients were enrolled into 5 cohorts in continuous regimen and 2 cohorts in 3-week-on/1-week-off regimen . The most common grade 3/4 adverse events were h and –foot skin reaction , hypertension , and thrombocytopenia . PK analysis showed good and rapid absorption followed by slow terminal elimination with a mean half-life of approximately 42 h which was consistent across all dose groups . Thirty-four patients were evaluable for tumor response , including 14 with partial response and 14 with stable disease . Conclusions Fruquintinib showed an acceptable safety profile and preliminary evidence of anti-tumor activity in patients with advanced solid tumors . The recommended dose was determined to be either 4 mg QD on a continuous regimen or 5 mg QD on a 3-week-on/1-week-off regimen 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 Abstract Objective To describe the use of regorafenib for the treatment of metastatic colorectal cancer ( mCRC ) in clinical practice in the Czech Republic , and to describe the clinical outcomes of patients in terms of safety and survival . Patients and Methods The data of patients treated with regorafenib were extracted from the national CORECT registry . The CORECT registry is a non-interventional post-marketing data base , gathering information about patients with CRC and treated with targeted agents . Twenty oncology centres in the Czech Republic contributed to this registry . Collected data included patients ’ characteristics , disease history , cancer treatments , response to treatments and safety . Results A total of 148 patients treated with regorafenib in clinical practice were analysed . At regorafenib initiation , almost all patients were fully active or slightly restricted in physical activity . Regorafenib was not administered as first-line treatment in any patient . Median progression-free survival was 3.5 months and median overall survival was 9.3 months . One-year survival rate was 44.6 % . Four partial responses were observed and 51 stable diseases . Progression was observed in 66 patients ( 44.6 % ) . The main reported adverse events were skin toxicity ( 5.4 % ) and fatigue ( 2.0 % ) . Conclusions Regorafenib is a well-established treatment for pretreated patients with mCRC , however real-life data are scarce . Our results demonstrated slightly better efficacy of regorafenib and better safety profile in patients with mCRC compared to the r and omised trials The FDA approved TAS-102 ( Lonsurf ; Taiho Oncology , Inc. ) for the treatment of patients with metastatic colorectal cancer ( mCRC ) who have been previously treated with fluoropyrimidine- , oxaliplatin- , and irinotecan-based chemotherapy ; an anti-VEGF biological therapy ; and if RAS wild type , an anti-EGFR therapy . In an international , multicenter , double-blinded , placebo-controlled trial ( TPU-TAS-102 - 301 , herein referred to as RECOURSE ) , 800 patients with previously treated mCRC were r and omly allocated ( 2:1 ) to receive either TAS-102 35 mg/m2 orally twice daily after meals on days 1 through 5 and 8 through 12 of each 28-day cycle ( n = 534 ) or matching placebo ( n = 266 ) . The trial demonstrated a statistically significant improvement in overall survival for those r and omized to receive TAS-102 , with a median survival of 7.1 months in the TAS-102 arm [ confidence interval ( CI ) , 6.5–7.8 ] and 5.3 months in the placebo arm [ CI , 4.6–6.0 ; hazard ratio ( HR ) , 0.68 ; 95 % CI , 0.58–0.81 ; P < 0.001 , stratified log-rank test ] . The trial also demonstrated a statistically significant prolongation of progression-free survival ( HR , 0.47 ; 95 % CI , 0.40–0.55 ; P < 0.001 ) . The most common adverse reactions , in order of decreasing frequency , observed in the patients who received TAS-102 were anemia , neutropenia , asthenia/fatigue , nausea , thrombocytopenia , decreased appetite , diarrhea , vomiting , abdominal pain , and pyrexia . Adverse events led to discontinuation of TAS-102 in 3.6 % of patients , and 13.7 % required a dose reduction . The most common adverse reactions leading to dose reduction were neutropenia , anemia , febrile neutropenia , fatigue , and diarrhea . Clin Cancer Res ; 23(12 ) ; 2924–7 . © 2017 AACR |
1,249 | 20,940,712 | The studies review ed consistently showed moderate diagnostic agreement between HBPM and ABPM , and superiority of HBPM compared to office measurements in diagnosing uncontrolled hypertension , assessing antihypertensive drug effects and improving patients ' compliance and hypertension control .
Preliminary evidence suggests that HBPM has the potential for cost savings .
CONCLUSIONS There is conclusive evidence that HBPM is useful for the initial diagnosis and the long-term follow-up of treated hypertension . | BACKGROUND It is recognized that for the reliable assessment of blood pressure ( BP ) and the accurate diagnosis of hypertension , out-of-office BP measurement with ambulatory ( ABPM ) or home BP monitoring ( HBPM ) is often required .
The clinical usefulness of ABPM is well established .
However , despite the wide use of HBPM , only in the last decade convincing evidence on its usefulness has accumulated . | This study investigated the differences in the effect of an angiotensin converting enzyme inhibitor ( ACEI ) compared with an angiotensin receptor blocker ( ARB ) on blood pressure ( BP ) and pulse pressure ( PP ) measured in the clinic ( CBP and CPP , respectively ) , at home ( HBP , HPP ) and with ambulatory monitoring ( ABP , APP ) . Twenty-seven hypertensive patients were r and omised to receive lisinopril ( 20 mg ) or losartan ( 50 mg ) for 5 weeks , and were subsequently crossed-over to the alternative treatment for a second 5-week period . Measurements of CBP , 24-h ABP and 5-days HBP were performed before r and omisation and at the end of each treatment period . All measurement methods showed that lisinopril was more effective than losartan in reducing BP . However , the difference between the two drugs was demonstrated with greater precision using HBP ( P<0.001 ) than 24-h ABP ( P<0.01 ) , whereas the poorest precision for demonstrating this difference was provided by CBP ( P<0.05 ) . Lisinopril was also found more effective than losartan in reducing HPP ( P=0.01 ) and 24-h APP ( P=0.03 ) whereas no such a difference was detected using measurements of CPP . It was concluded that the antihypertensive drugs may differ in their effects not only on BP , but also on PP . HBP monitoring appears to be as reliable as 24-h ABP monitoring in detecting differences in the effect of drugs on both BP and PP . Clinic measurements seem to be the least reliable method , particularly in the detection of differences in PP Office , home , and ambulatory blood pressure ( BP ) demonstrate variable associations with outcomes . The authors sought to compare office BP ( OBP ) , home BP ( HBP ) , and ambulatory BP ( ABP ) for measuring responses to hydrochlorothiazide ( HCTZ ) , atenolol , and their combination . After completing washout , eligible patients were r and omized to atenolol 50 mg or HCTZ 12.5 mg daily . Doses were doubled after 3 weeks and the alternate drug was added after 6 weeks if BP was > 120/70 mm Hg ( chosen to allow maximum opportunity to assess genetic associations with dual BP therapy in the parent study ) . OBP ( in triplicate ) , HBP ( twice daily for 5 days ) , and 24-hour ABP were measured at baseline , after monotherapy , and after combination therapy . BP responses were compared between OBP , HBP , and ABP for each monotherapy and combination therapy . In 418 patients , OBP overestimated BP response compared with HBP , with an average 4.6 mm Hg greater reduction in systolic BP ( P<.0001 ) and 2.1 mm Hg greater reduction in diastolic BP ( P<.0001 ) across all therapies . Results were similar for atenolol and HCTZ monotherapy . ABP response was more highly correlated with HBP response ( r=0.58 ) than with OBP response ( r=0.47 ; P=.04 ) . In the context of a r and omized clinical trial , the authors have identified significant differences in HBP , OBP , and ABP methods of measuring BP response to atenolol and HCTZ monotherapy It is still uncertain whether one can safely base treatment decisions on self-measurement of blood pressure . In the present study , we investigated whether antihypertensive treatment based on self-measurement of blood pressure leads to the use of less medication without the loss of blood pressure control . We r and omly assigned 430 hypertensive patients to receive treatment either on the basis of self-measured pressures ( n=216 ) or office pressures ( OPs ; n=214 ) . During 1-year follow-up , blood pressure was measured by office measurement ( 10 visits ) , ambulatory monitoring ( start and end ) , and self-measurement ( 8 times , self-pressure group only ) . In addition , drug use , associated costs , and degree of target organ damage ( echocardiography and microalbuminuria ) were assessed . The self-pressure group used less medication than the OP group ( 1.47 versus 2.48 drug steps ; P<0.001 ) with lower costs ( $ 3222 versus $ 4420 per 100 patients per month ; P<0.001 ) but without significant differences in systolic and diastolic OP values ( 1.6/1.0 mm Hg ; P=0.25/0.20 ) , in changes in left ventricular mass index ( -6.5 g/m(2 ) versus -5.6 g/m(2 ) ; P=0.72 ) , or in median urinary microalbumin concentration ( -1.7 versus -1.5 mg per 24 hours ; P=0.87 ) . Nevertheless , 24-hour ambulatory blood pressure values at the end of the trial were higher in the self-pressure than in the OP group : 125.9 versus 123.8 mm Hg ( P<0.05 ) for systolic and 77.2 versus 76.1 mm Hg ( P<0.05 ) for diastolic blood pressure . These data show that self-measurement leads to less medication use than office blood pressure measurement without leading to significant differences in OP values or target organ damage . Ambulatory values , however , remain slightly elevated for the self-pressure group Background Gender , age , smoking , race , and body mass index have been reported to determine the ambulatory white-coat effect ( WCE ) and white-coat hypertension ( WCH ) . Methods Baseline conventional , day-time ambulatory and self-measured home blood pressure measurements from the THOP trial were used to study the effect of gender , age , body mass index , smoking habits and treatment status on the white-coat syndrome as assessed by ambulatory monitoring or self-measurement . Results The mean systolic/diastolic WCE was 9.1/6.7 mmHg if based on ambulatory blood pressure and 12.2/8.7 mmHg if based on self-measured blood pressure . The ambulatory WCE was significantly higher in women , in older subjects ( 65 + ) , in obese subjects , in non-smokers and in patients on antihypertensive drug treatment . The self-measured WCE was significantly higher in women and in non-smokers . Ambulatory WCH was present in 6.6 % of the untreated patients and 14.2 % had self-measured WCH . The proportion of ambulatory WCH was significantly higher in obese subjects ; the proportion of self-measured WCH did not differ by gender , age , body mass index , or smoking habits . Conclusions The ambulatory white-coat syndrome was determined by gender , age , body mass index , smoking habits , and treatment status . The self-measured white-coat syndrome was greater than the ambulatory white-coat syndrome but depended less on the determinants under study Background —The prevalence and clinical significance of isolated office ( or white coat ) hypertension is controversial , and population data are limited . We studied the prevalence of this condition and its association with echocardiographic left ventricular mass in the general population of the PAMELA ( Pressione Arteriose Monitorate E Loro Associazioni ) Study . Methods and Results —The study involved a large , r and omized sample ( n=3200 ) representative of the Monza ( Milan ) population , 25 to 74 years of age . Participants in the study ( 64 % of the sample ) underwent measurements of office , home , 24-hour ambulatory blood pressure , and echocardiography . Isolated office hypertension was defined as systolic or diastolic values ≥140 mm Hg or ≥90 mm Hg , respectively . Home and ambulatory normotension were defined according to criteria previously established from the PAMELA Study , for example , < 132/83 mm Hg ( systolic/diastolic ) for home and 125/79 mm Hg for 24-hour average blood pressure . Treated hypertensive subjects were excluded from analysis that was made on a total of 1637 subjects . Depending on normotension being established on systolic or diastolic blood pressure measured at home or over 24 hours , the prevalence of isolated office hypertension ranged from 9 % to 12 % . In these subjects , left ventricular mass index was greater ( P < 0.01 ) than in subjects with normotension both in and outside the office . This was the case also for prevalence of left ventricular hypertrophy . Left ventricular mass index and hypertrophy were similarly greater in subjects found to have normal office but elevated home or ambulatory blood pressure ( ≈10 % of the population ) . Conclusions —Isolated office hypertension has a noticeable prevalence in the population and is accompanied by structural cardiac alterations , suggesting that it is not an entirely harmless phenomenon . This is the case also for the opposite condition , that is , normal office but elevated home or ambulatory blood pressure , which implies that limiting blood pressure measurements to office values may not suffice in identification of subjects at risk BACKGROUND Our objective was to assess the value of home blood pressure ( BP ) monitoring in comparison to office BP measurements and ambulatory monitoring in predicting hypertension-induced target-organ damage . METHODS Sixty-eight untreated patients with hypertension with at least two routine pre study office visits were included ( mean age , 48.6 + /- 9.1 [ SD ] years ; 50 men ) . Office BP was measured in two study visits , home BP was measured for 6 workdays , and ambulatory BP was monitored for 24 h. All BP measurements were obtained using vali date d electronic devices . Target-organ damage was assessed by measuring the echocardiographic left-ventricular mass index ( LVMI ) , urinary albumin excretion rate ( AER ) in two overnight urine collection s , and carotid-femoral pulse-wave velocity ( PWV ) ( Complior device ; Colson , Garges-les-Gonesse , Paris , France ) . RESULTS The correlation coefficients of LVMI with office BP were 0.24/0.15 ( systolic/diastolic ) , with home BP 0.35/0.21 ( systolic , P < .01 ) , and with 24-h ambulatory BP 0.23/0.19 , awake 0.21/0.16 , and asleep 0.28/0.26 ( asleep , both P < .05 ) . The correlation coefficients of AER with office BP were 0.24/0.31 ( diastolic , P < .05 ) , with home BP 0.28/0.26 ( both P < .05 ) , and with 24-h ambulatory BP 0.25/0.24 , awake 0.24/0.25 ( diastolic , P < .05 ) , and asleep 0.26/0.18 ( systolic , P < .05 ) . There was a trend for negative correlations between PWV and diastolic BP measurements ( not significant ) . In multiple-regression models assessing independent predictors of each of the three indices of target-organ damage , systolic home BP and age were the only independent predictors of increased LVMI that reached borderline statistical significance . CONCLUSIONS These data suggest that home BP is as reliable as ambulatory monitoring in predicting hypertension-induced target-organ damage , and is superior to carefully taken office measurements BACKGROUND Because of poor patient compliance and clinical inertia , hypertension control rates remain poor . Home blood-pressure measurements ( HBPM ) improve compliance of patients and achievement of blood pressure ( BP ) targets . However , few studies have evaluated self-BP management by patients . METHODS In a multicenter , prospect i ve , single-group , open-label pilot study of 111 patients whose hypertension was uncontrolled despite monotherapy , we studied satisfaction with , and feasibility of , HBPM and self-titration of antihypertensive treatment using telemedicine for compliance , efficacy , and safety . After education ( protocol , action plan , and use of the HBPM device ) , patients performed a sequence of HBPM every 2 weeks for 8 weeks . Following a stepwise approach , treatment was increased by the patient at weeks 4 and 6 if average HBPM values exceeded predefined limits . For each titration , the patient informed the Core Center by telemedicine , but BP values were transferred automatically . RESULTS Overall , 80 % of patients were satisfied ( 58 % ) or very satisfied ( 23 % ) with the program ( 95 % confidence interval , 73 % to 87 % ) . Regarding compliance , 78 % of patients fully complied with self-measurement , and just over 71 % titrated their treatment adequately . Physicians were satisfied ( 52 % ) or very satisfied ( 22 % ) with the program . Between the first and final visits ( at week 8) , office systolic/diastolic BP ( mean + /- SD ) decreased significantly from 151 + /- 9/91 + /- 6 to 143 + /- 13/84 + /- 11 mmHg . During the trial , HBPM ( mean + /- SD ) decreased significantly from 149 + /- 13/86 + /- 12 to 138 + /- 16/81 + /- 10 mmHg . No significant safety issues were reported . CONCLUSIONS This innovative approach to the management of hypertension , combining self-measurement and self-titration , is feasible , well-accepted by both patients and physicians , and safe BACKGROUND Home blood pressure ( BP ) monitoring improves BP control , but it is unknown whether patients accurately report home BP readings to their physician . This study compared self-reported with electronically stored home BP and heart rate ( HR ) readings and evaluated this agreement in patients with controlled vs. uncontrolled hypertension . METHODS A single-blind , r and omized clinical trial was conducted in an ambulatory managed care population . Subjects were identified by hypertension-related codes from the International Classification of Diseases , Ninth Revision ( 401.0 , 401.1 , and 401.9 ) . Subjects recorded systolic BP ( SBP ) , diastolic BP ( DBP ) , and HR 3 times daily for 1 week by means of a digital BP monitor . Subjects were unaware that the monitor electronically stored results . RESULTS Thirty subjects were enrolled ( 29 complete data sets ) ; their mean age ( + /-SD ) was 56+/-9 years , and 15 ( 52 % ) were women . Sixty-eight percent of subject-recorded SBP , DBP , and HR measurements were identical to electronically stored results . Twenty percent of recorded SBPs and 17 % of recorded DBPs differed from stored SBP and DBP by more than 10 mm Hg . Erroneous reporting was evident in 9 % of uncontrolled vs 4 % of controlled SBPs ( P<.001 ) . Similarly , 21 % of uncontrolled and 4 % of controlled DBPs were erroneously reported ( P<.001 ) . In cases where the stored HR exceeded 100 beats/min , 43 % of HR readings were recorded as 100 beats/min or less ( P<.001 ) . CONCLUSIONS Most self-reported BP and HR readings were identical to electronically stored measurements . However , erroneous reporting occurred significantly more often in cases of uncontrolled BP and HR , which may misguide physicians in the optimal treatment of their patients with hypertension Aim . To compare the effectiveness of antihypertensive treatment based on telemonitoring of home blood pressure ( BP ) and conventional monitoring of office BP . Methods . Hypertensive patients ( n = 236 ) participated in a r and omized , controlled study . In the intervention group , antihypertensive treatment was based on home BP monitoring . BP readings were registered by a PDA and automatically transmitted to a server , by which the patient and doctor could communicate . In the control group , patients received usual care with office visits to adjust antihypertensive treatment as needed . Primary outcome was difference in systolic daytime ambulatory BP monitoring ( ABPM ) change between baseline and 6 months . Results . In both groups , systolic daytime ABPM decreased significantly from baseline to follow‐up . The decrease in systolic daytime ABPM was −11.9 mmHg in the intervention group and −9.6 mmHg in the control group ( mean difference −2.3 [ 95 % CI −6.1 to −1.5 ] , p = 0.225 ) . The likelihood of daytime ABPM normalization was similar in the two groups [ 32/113 ( 28 % ) vs 46/123 ( 37 % ) , p = 0.139 ] . Conclusion . Antihypertensive treatment based on telemonitoring of home BP was as effective as usual monitoring of office BP with regards to reduction of BP . Trial registration : Clinical Trials.gov identifier : NCT00282334 The reproducibility of ambulatory , home , and clinic blood pressures was compared in 13 untreated mildly hypertensive and 14 normotensive subjects . Each subject had two sets of daily ambulatory recordings , home self-measured readings ( over 6 days ) , and clinic measurements taken 2 weeks apart . Comparisons over the 2 weeks within and among the methods of measurements were made using a repeated- measures analysis of variance . The results showed that there was no consistent average change in the ambulatory or home pressures and no change in clinic diastolic pressures , but the clinic systolic pressure of the hypertensive subjects dropped 6 mm Hg ( p less than 0.05 ) , while that of the normotensive subjects showed no significant change . Test-retest correlations of each of the three methods were similar in magnitude , indicating a similar level of reliability . Test-retest correlations of the ambulatory st and ard deviations , however , were low , indicating a low reliability of this measure of daily pressure variability . These results suggest that the reproducibility of ambulatory pressures may be as good or better than that of home or clinic measurements . They also suggest that the average ambulatory pressure may be preferable as the measurement in clinical trials , since it may be less influenced by measurement anxiety , particularly in hypertensive subjects Several studies compared blood pressure ( BP ) at home ( HBP ) with ambulatory BP ( ABP ) , but using different devices , which contribute to differences in measured BP . A novel dual-mode device allowing ABP and HBP monitoring ( Microlife WatchBPO3 ) was vali date d according to the European Society of Hypertension International Protocol and used to compare the two methods . In the validation study , 33 subjects were assessed with simultaneous BP measurements taken by 2 observers ( connected mercury sphygmomanometers ) 4 times , sequentially with 3 measurements taken using the tested device . Absolute observer-device BP differences were classified within 5/10/15 mm Hg zones . Measurements with ⩽5 mm Hg difference were calculated per participant . In the validation study , the device produced 70/89/96 measurements within 5/10/15 mm Hg , respectively , for systolic BP and 67/95/99 for diastolic BP . Twenty-eight subjects had at least two of their systolic BP differences ⩽5 mm Hg and one subject had no difference ⩽5 mm Hg , whereas for diastolic BP , it was 22 and 1 subjects , respectively . Mean device-observers BP difference was −0.3±5.6/−2.4±4.8 mm Hg ( systolic/diastolic ) . In the application study , the difference between daytime ABP and HBP was 0.5±7.9 mm Hg for systolic BP ( mean±st and ard deviation , 95 % confidence intervals ( CI ) −1.9 , 2.9 , P = NS ) and 0.6±5.5 for diastolic BP ( 95 % CI −1.1 , 2.3 , P = NS ) . In conclusion , the Microlife WatchBPO3 device for ABP and HBP monitoring fulfils the International Protocol validation criteria . Using this device , no clinical ly important difference between daytime ABP and HBP was detected . These data justify the use of the same diagnostic threshold for both methods Objective To determine the minimum number of self- measurements of blood pressure at home ( HBP ) necessary to provide the maximum clinical ly important benefit . Methods Hypertensive patients were r and omly allocated to monitor HBP for 2 weeks ( 6 work days , duplicate measurements , twice daily ) or ambulatory blood pressure for 24 h. The alternative measurement was then performed . Clinic blood pressure was measured at the beginning and the end of the study . Criteria for reliability of HBP were the stabilization of mean HBP , its variability ( SD ) and the correlation coefficient r for relationship of HBP with ambulatory blood pressure . The reproducibility of HBP was quantified using test – re-test correlations and the SD of differences between average HBP values of different days . Results We studied 189 patients ( 79 being administered stable antihypertensive treatment ) . Average HBP ( 137.5 ± 16.2/85.9 ± 9.9 mmHg ) was lower than average clinic blood pressure ( P < 0.001 ) and higher than 24 h and night-time ambulatory blood pressures ( P < 0.001 ) . There was no difference between HBP and daytime ambulatory blood pressure . On day 1 HBP was higher than it was on each of days 2–6 , with no difference among days 2–6 . When data for the initial day for monitoring of HBP were excluded from analysis , average HBP was reduced . Only a modest improvement in the reliability of HBP on day 2 ( reductions in mean HBP and its SD and an increase in r with ambulatory blood pressure ) was achieved by averaging more readings taken on succeeding days . At least two monitoring days were needed for the reproducibility of HBP to be superior to that of clinic blood pressure . Conclusions These results suggest that determining average HBP of the second and third work days , is the minimum programme that provides a reliable estimate of HBP An algorithm has been proposed for the detection of white coat hypertension among subjects with elevated blood pressure ( BP ) on at least three clinic visits using home BP monitoring ( screening test ) and , if this is low , ambulatory BP monitoring ( diagnostic test ) . This study aims to test this strategy in practice . The proposed algorithm was applied in 133 untreated subjects with elevated BP assessed in a previous prospect i ve study using repeated clinic , home and ambulatory BP measurements . The proportions of detected and missed cases of white coat hypertension and the diagnostic value of the algorithm were calculated . By applying the algorithm , 99 subjects ( 74 % ) were found eligible for home measurements and 35 ( 26 % ) for ambulatory monitoring . There were 38 subjects with white coat hypertension ( 38 % ) , of whom 15 ( 39 % ) were not detected by the proposed strategy . The sensitivity , specificity , and the positive and negative predictive value of the algorithm to diagnose white coat hypertension were 61 , 81 , 66 and 77 % , respectively . Of the 34 subjects with normal BP on the third clinic visit , 15 ( 42 % ) had elevated home and /or ambulatory BP . These data suggest that , using the proposed strategy , many white coat hypertensives may remain undetected and may receive unnecessary long-term drug treatment . Therefore , more research is needed on the optimal strategy for detecting white coat hypertension in clinical practice In a double-blind , within-patient study , blood pressure was measured at regular intervals at the clinic by the physician and each day at home by the patient . Both methods of blood pressure measurement demonstrated an antihypertensive effect of the diuretics chlorthalidone ( 25 mg ) and triamterene ( 50 mg ) and the beta-blocker oxprenolol ( 160 mg ) and the greater efficacy of the combination of the two therapies . During placebo , as well as during active treatment , blood pressure values were higher at the clinic than at home , except when the patients were taking the beta-blocker , which minimized the arousal response during blood pressure measurements in the clinic . With 2-week treatment periods , separated by 2 weeks of placebo administration , blood pressure returned toward its initial level after each of the three treatments and none of the carryover effects was significant at the 5 % level . This methodology was intended to make it possible to demonstrate in 27 patients at the clinic and in 20 patients with measurements made at home , at the usual statistical risks ( alpha = 5 % , beta = 10 % ) , a fall of 5 mm Hg in diastolic blood pressure in comparison with a placebo . Moreover , at the end of this 3-month follow-up , each patient could continue to receive the treatment that was the most effective and the best tolerated . In conclusion , the use of a within-patient trial design , with a 15-day washout period between active treatments and careful recording of blood pressure values , can minimize the number of patients included in hypertension trials and offer to each patient the possibility of individualization of treatment Objectives The use of low-dose amlodipine has not yet been well established in the elderly . This study therefore aim ed to evaluate the efficacy and tolerability of low-dose amlodipine in elderly patients with Joint National Committee VI stage I or II hypertension . Patients and methods Sixty-five hypertensive individuals ( aged 66.3±5.3 years ) received amlodipine 2.5 mg per day for 12 weeks before and after two periods of 4 weeks of placebo . At weeks 0 , 12 and 16 , patients were su bmi tted to office , 24 h ambulatory blood pressure monitoring and home blood pressure measurement . Results Office systolic and diastolic blood pressure showed decreases at weeks 8 ( 153±17 , 90±9 mmHg ) and 12 ( 152±16 , 90±9 mmHg ) compared with weeks 0 ( 164±16 , 99±6 mmHg ) and 16 ( 162±19 , 95±9 mmHg ) . During ambulatory monitoring , a decrease was observed in the average 24 h systolic and diastolic pressure at week 12 ( 143±13 , 86±7 mmHg ) compared with weeks 0 ( 155±15 , 93±6 mmHg ) and 16 ( 152±16 , 92±8 mmHg ) . A daytime and night-time reduction in systolic and diastolic pressure was observed on home blood pressure monitoring at week 12 ( 146±16/88±8 , 144±16/93±8 mmHg ) compared with weeks 0 ( 159±17/94±8 , 161±19/93±8 mmHg ) and 16 ( 153±16/93±8 , 154±17/92±8 mmHg ) . Adverse reactions were infrequent . Conclusions Amlodipine at a dose of 2.5 mg per day showed efficacy and good tolerability in elderly hypertensives BACKGROUND The majority of hypertensive patients do not reach the target blood pressure ( BP ) . We sought to clarify whether intermittent self-monitoring of BP leads to better BP control compared to ordinary treatment in general practice . METHODS Two hundred sixty-nine hypertensive patients participated in this multicenter , r and omized , parallel-group study in primary health care . Home BP was measured in the self-monitoring ( SM ) group at 0 , 2 , 4 , and 6 months , and in the control ( C ) group at 0 and 6 months . The participating physicians were instructed to intensify the antihypertensive therapy when needed . RESULTS At the beginning , both groups had similar home BP levels ( SM 143.1 + /- 17.4/85.3 + /- 7.4 mm Hg v C 143.9 + /- 18.3/85.4 + /- 7.5 mm Hg ) . After 6 months , there were significant decreases in systolic ( P < or= .0001 ) , diastolic ( P < or= .0029 ) , and pulse pressures ( P < or= .021 ) in both groups . Systolic ( -7.8 + /- 13.1 mm Hg v -4.5 + /- 12.2 mm Hg , P = .047 ) and pulse pressure ( -4.7 + /- 9.0 mm Hg v -2.2 + /- 10.0 mm Hg , P = .042 ) decreased significantly more than in the self-monitoring group . The decrease in diastolic pressure was similar in both groups ( SM -3.1 + /- 6.2 mm Hg v C -2.3 + /- 8.3 mm Hg , P = not significant ) . The patients in the SM group reached home BP target more often than those in the C group ( 29 % v 16 % , P = .016 ) . There was a nonsignificant trend toward lower office BP values in the SM group . CONCLUSIONS Self-monitoring decreased systolic and pulse pressure significantly more than ordinary treatment and promoted achievement of target BP . This was most likely due to improved patient compliance and more active treatment by the physicians . Our results suggest that home measurement is useful in the control of hypertension BACKGROUND Hemodialysis patients have a steady increase in blood pressure ( BP ) during the 44-hour interdialytic interval when ambulatory BP monitoring is used . Home BP recording allows for a longer period of monitoring between dialysis treatments and may better define the chronobiological characteristics of arterial hypertension . This study sought to determine the optimal time to perform home BP monitoring in hemodialysis patients to improve the strength of prediction of 44-hour interdialytic ambulatory BP . STUDY DESIGN Diagnostic test study . SETTING & PARTICIPANTS This is an ancillary analysis of patients participating in the Dry-weight Reduction in Hypertensive Hemodialysis Patients ( DRIP ) trial . INDEX TEST Home BP measured 3 times daily for 1 week by using a vali date d oscillometric monitor on 3 occasions at 4-week intervals after r and omization . Home BP measured during the first third , second third , and last third of time elapsed after the dialysis treatment , as well as each third of the dialysis treatment , was compared with the overall ambulatory BP . REFERENCE TESTS Interdialytic ambulatory BP measured on 3 occasions at 4-week intervals after r and omization . RESULTS During the interdialytic interval , we found an increase in systolic ambulatory BP of 0.30 + /- 0.36 mm Hg/h and an increase in systolic home BP of 0.40 + /- 0.25 mm Hg/h . This relationship in home BP reached a plateau after approximately 48 hours . A similar pattern was seen for diastolic home BP . Probing dry weight steepened the slope of ambulatory BP , but did not alter the time-dependent relationship of home BP . Home BP was on average higher ( bias ) by 14.1 ( 95 % confidence interval , 12.0 to 16.2)/5.7 mm Hg ( 95 % confidence interval , 4.6 to 6.9 ) . The SD of differences between methods ( precision ) was 4.6/2.8 mm Hg . Measurement of BP during each third of the interdialytic interval gave the best precision , measured by using model fit compared with ambulatory BP measurements . LIMITATIONS Our cohort was overrepresented by African American hemodialysis patients . Whether African American participants have a different pattern of BP response than non-African American participants in the interdialytic period is not known . CONCLUSIONS Our findings suggest that time elapsed after a dialysis treatment must be considered in interpreting home BP recordings in hemodialysis patients . Home BP measured in each third of the interdialytic interval is likely to yield the most reliable BP estimate BACKGROUND In cross-sectional studies , ambulatory blood pressure ( ABP ) correlates more closely than clinic BP with the organ damage of hypertension . Whether ABP predicts development or regression of organ damage over time better than clinic BP , however , is unknown . METHODS AND RESULTS In 206 essential hypertensive subjects with left ventricular hypertrophy ( LVH ) , we measured clinic supine BP , 24-hour ABP , and left ventricular mass index ( LVMI , echocardiography ) before and after 12 months of treatment with lisinopril ( 20 mg UID ) without or with hydrochlorothiazide ( 12.5 or 25 mg UID ) . Measurements included r and om-zero , clinic orthostatic , and home BP . In all , 184 subjects completed the 12-month treatment period . Before treatment , clinic supine BP was 165 + /- 15/105 + /- 5 mm Hg ( systolic/diastolic ) , 24-hour average BP was 149 + /- 16/95 + /- 11 mm Hg , and LVMI was 158 + /- 32 g/m2 . At the end of treatment , they were 139 + /- 12/87 + /- 7 mm Hg , 131 + /- 12/83 + /- 10 mm Hg , and 133 + /- 26 g/m2 , respectively ( P < .01 for all ) . Before treatment , LVMI did not correlate with clinic BP , but it showed a correlation with systolic and diastolic 24-hour average BP ( r = .34/.27 , P < .01 ) . The LVMI reduction was not related to the reduction in clinic BP , but it was related to the reduction in 24-hour average BP ( r = .42/.38 , P < .01 ) . Treatment-induced changes in average daytime and nighttime BPs correlated with LVMI changes as strongly as 24-hour BP changes . No substantial advantage over clinic supine BP was shown by clinic orthostatic , r and om-zero , and home BP . CONCLUSIONS In hypertensive subjects with LVH , regression of LVH was predicted much more closely by treatment-induced changes in ABP than in the clinic BP . This provides the first longitudinally controlled evidence that ABP may be clinical ly superior to traditional BP measurements In recent years self-measurement of blood pressure at home has gained increasing importance but there have been only a few studies comparing casual , ambulatory , and self-measured blood pressure determinations during a single clinical trial . We therefore compared treatment-induced blood pressure-reductions in a double-blind , placebo-controlled , parallel study design with a single morning dose of either 10 mg bisoprolol ( n = 26 ) or 20 mg nitrendipine ( n = 27 ) with casual blood pressure readings in the morning before the dose , ambulatory 24-h monitoring , and self-recorded measurements in the morning before the dose and in the evening . Mean reductions for systolic and diastolic blood pressure after 4 weeks of therapy were significantly greater for bisoprolol than for nitrendipine . The treatment-induced blood pressure reductions were most pronounced as assessed by casual readings but showed good agreement between casual , ambulatory , and self-measured blood pressure for group comparisons . In some patients , however , marked individual differences between the three methods were observed . Correlation coefficients between ambulatory and self-measured blood pressure were 0.4 for systolic blood pressure ( P less than .05 ) and 0.6 for diastolic blood pressure ( P less than .0005 ) . Under the conditions of this parallel study design and the usual statistical risks , a difference of 5 mm Hg in diastolic blood pressure can be detected in 118 patients at the clinic , in 70 patients if ambulatory blood pressure is used , or in 56 patients if self-measured blood pressure is used . In conclusion , bisoprolol was more effective over 24 h than nitrendipine at the doses studied . ( ABSTRACT TRUNCATED AT 250 WORDS Objectives Reproducibility of home blood pressure measurements ( HBP ) , and the placebo effect on HBP , were examined to establish the number of subjects required in order to observe a significant antihypertensive effect of a drug for a comparative study between placebo and active treatment . Methods Reproducibility of HBP ( n = 172 for systolic blood pressure and n = 137 for diastolic blood pressure ) and the placebo effect on HBP ( n = 35 for systolic and n = 42 for diastolic blood pressure ) were examined using a semi-automatic electronic device on untreated hypertensive subjects during 21 consecutive days of measurements . From these two studies , the number of subjects required in order to observe a significant antihypertensive drug effect was assessed . In both studies , measurements from the first 3 days were excluded from the analysis . Results Reproducibility , defined as the difference between the initial 5 day average ( days 4–8 ) and the last 5 day average ( days 17–21 ) was −1.9 ± 7.0/–1.4 ± 4.8 mmHg ( mean ± SD ) , indicating high reproducibility with a minimal regression to the mean effect . A placebo was administered after the 8 day run-in period . The difference between the initial 5 day average ( days 4–8 ) and the last 5 day average ( days 17–21 ) was compared . The mean difference was 1.1 ± 6.2/0.2 ± 5.7 mmHg , suggesting that there was a minimal , if any , placebo effect . As determined by the power calculations , based on the st and ard deviations of the tests for reproducibility and the placebo effect , nine of 13 subjects are required to show that a 9/5 mmHg decrease in systolic HBP/diastolic HBP ( 50 % of estimated effective decrease in systolic HBP/diastolic HBP according to the guidelines for clinical trials in Japan ) is statistically significant . Conclusions The results suggest that the HBP measurement is highly reproducible and that there is a minimal , if any , placebo effect . These characteristics of HBP contribute to minimizing the number of subjects necessary for assessment of antihypertensive drug effects in comparative studies between an active treatment and placebo This study aim ed to compare the efficacy of a patient-directed management strategy with office-based management in maintaining blood pressure control in patients with chronic stable hypertension using a r and omized trial of two months duration . The subjects had chronic stable essential hypertension without secondary causes or unstable cardiovascular disease and were selected through the offices of 11 family physicians and a tertiary care hypertension research unit . Patients were r and omly assigned ( 2:1 ratio ) to either a patient-directed management strategy using home blood pressure monitoring to adjust drug therapy if readings consistently exceeded defined limits , or office-based management through physician visits . The primary endpoint was the change from baseline in mean arterial pressure as determined by automatic ambulatory blood pressure monitoring . Secondary endpoints were changes in compliance , quality of life , and health care re source use . Ninety-one potential subjects were screened and 31 were r and omized . Subjects in the patient-directed management group employed the drug adjustment protocol s appropriately without complications . A significant difference in change in mean blood pressure was observed , favoring the patient-directed management ( -0.95 mm Hg and + 1.90 mm Hg , respectively , for patient-directed management and office-based management , P = .039 ) . Compliance rates and quality of life scores were not significantly different between groups . Physician visits were more frequent in the patient-directed management group ( 1.05 v 0.20 visits/8 weeks , respectively , for patient-directed management and office-based management groups , P = .045 ) . A patient-directed hypertensive management strategy may be feasible for patients with chronic stable hypertension . Such a strategy may improve blood pressure control compared with usual office-based care . However , physician visits may be increased using this strategy , at least in the short term Cross-sectional studies have shown that home blood pressure ( BP ) correlates with hypertensive target organ damage better than clinic BP . However , there have been few longitudinal studies regarding the predictive value of home BP on the changes in organ damage in treated hypertensive patients . Clinic and home BP over a 12-month period , antihypertensive medication use , echocardiographic and electrocardiographic results , and serum creatinine and urinary protein levels were examined in 209 treated hypertensive patients in 1993 . These patients were prospect ively followed for 5 years . The patients were divided into 4 subgroups according to hypertension control as follows : good control ( < 140/90 mmHg for clinic BP , < 135/85 mmHg for home BP ) , improved , worsened , and poor control . The average clinic BP was 147.0+/-14.9/87.0+/-7.6 mmHg ( mean+/-SD ) in 1993 and 146.0+/-13.7/84.1+/-7.5 mmHg in 1998 . The average home BP was 136.8+/-10.4/84.3+/-7.6 mmHg in 1993 and 136.1+/-9.7/81.2+/-7.7 mmHg in 1998 . The left ventricular mass index ( LVMI ) positively correlated with both home systolic BP and clinic systolic BP in 1998 but not in 1993 . The correlation tended to be closer for home BP than for clinic BP . LVMI did not change in patients with good or improved home systolic BP , while it increased in those with poor or worsened home systolic BP . The relationship between changes in LVMI and clinic BP was not significant . In conclusion , Home BP was more effective than clinic BP as a predictor of changes in left ventricular hypertrophy in treated hypertensive patients . Home BP should be controlled to below 135/85 mmHg to prevent cardiac hypertrophy Objective Guidelines recommend home blood pressure monitoring ( HBPM ) to improve blood pressure control , but the attitudes of primary care physicians and their hypertensive patients towards its use are not known . Methods A 28-item self-administered survey about home blood pressure monitoring was mailed to a r and om sample of 1418 primary care physicians in Ontario and 765 ( 55 % ) were returned . Of the 478 physicians treating hypertension , 299 agreed to give surveys to their hypertensive patients . We received 149 patient surveys . Results The majority of primary care physicians ( 63 % ) often or almost always encouraged their hypertensive patients to monitor their own blood pressure at home . Only 13 % , however , preferred home blood pressure monitoring to office or ambulatory readings for diagnostic purpose s and 19 % , to guide therapy . Physicians had concerns about patients becoming preoccupied with home monitoring ( 70 % ) and the accuracy of home devices ( 65 % ) . Most patients ( 78 % ) had a device at home , and 84 % indicated that their doctor encouraged them to measure blood pressure . Yet , 80 % received no advice from their physician on the type of device to purchase , only 8 % had specific training on proper measurement technique , 68 % did not regularly take the results to the doctor and 39 % did nothing specific about alarming readings . Conclusions Primary care physicians prefer office or ambulatory to home readings to make diagnostic and therapeutic decisions . While home monitoring is popular among patients , its clinical usefulness is undermined by the lack of reliable purchasing information , st and ard measurement protocol s , proper training on measurement technique and specific instructions on h and ling and interpreting results The objective of the study was to investigate whether home blood pressure ( HBP ) is a reliable alternative to ambulatory blood pressure ( ABP ) for the detection of the white coat effect ( WCE ) . Hypertensive patients were r and omized to measure HBP for 2 weeks or ABP for 24 h. The alternative measurement was then performed . Clinic blood pressure ( CBP ) was measured in the beginning and end of the study . Subjects with a difference of > or = 20 mm Hg systolic or > or = 10 mm Hg diastolic BP between CBP and awake ABP or CBP and HBP , were classified as clinic reactors . A total of 189 patients completed the study ( 79 on stable antihypertensive treatment ) . There was no difference in the magnitude of WCE assessed using the ABP or the HBP method ( mean discrepancy , systolic BP : -1.5 + /- 11.7 mm Hg , 95 % CI -3.2 , 0.2 ; diastolic BP : 0.9 + /- 7.0 , 95 % CI -0.1 , 1.9 ) . A strong association existed between WCE calculated using the HBP or the ABP method ( r = 0.64/0.59 systolic/diastolic , P < .001 ) . The proportion of patients classified as clinic reactors was identical using the HBP or the ABP method ( 25.9 % ) . Agreement between methods in the classification of clinic reactors was found in 147 patients ( 78 % ) . The sensitivity and specificity of the HBP method to classify correctly clinic reactors ( ABP method used as the st and ard ) were 57 % and 85 % , respectively , whereas its positive and negative predictive value were 57 % and 85 % . These results indicate that HBP is not appropriate as an alternative to ABP diagnostic testing in the detection of WCE . Nevertheless , HBP appears useful as a screening test for the detection of this phenomenon Aim Studies were carried out to assess ( 1 ) the statistical and clinical meaning of the trough : peak ratio and ( 2 ) the value of self-measurement of blood pressure at home in monitoring the duration of action of antihypertensive drugs in individual patients and in groups of patients . Patients and methods Data from previous single-blind trials in 44 individual patients were reanalysed . The trough : peak ratio was calculated from mean blood pressure values . Results There are two major limitations in using this method . ( 1 ) Estimates of the trough : peak ratio are biased by the inclusion of non-responders . These patients have the usual r and om variations in blood pressure , and small differences can result in a spuriously high trough : peak ratio which may lead to an overestimate of the actual ratio . ( 2 ) The st and ard deviation of the trough : peak ratio is large ; for a given mean trough : peak ratio some patients have the required 24-h drug cover , whereas others do not . The large st and ard deviation is partly a result of statistical problems , since four different blood pressure values are used to calculate the ratio . It is therefore essential to increase the precision of the measurement to decrease the st and ard deviation . Conclusions Self-measurement of blood pressure at home might be a useful and inexpensive way of estimating the trough : peak ratio . As repeated measurements of blood pressure can be carried out at home under st and ardized conditions , this method increases the precision of each measurement . It is possible , therefore , to calculate individual trough : peak ratios and the drug regimen ( once or twice a day ) can be individualized The objective of this study was to determine whether a hypertension management program in which patients monitor their own blood pressure ( BF ) at home can reduce costs without compromising BP control . The prospect i ve , r and omized , controlled 1-year clinical trial was conducted at four medical centers of the Kaiser Permanente Medical Care Program in the San Francisco Bay Area . Of 467 patients with uncomplicated hypertension who were referred by their physicians , 37 declined to participate in the study ; 215 were r and omly assigned to a Usual Care ( UC ) group and 215 to a Home BP group . Twenty-five UC patients and 15 Home BP patients did not return for year-end BP measurements . Patients in the UC group were referred back to their physicians . Patients in the Home BP group were trained to measure their own BP and return the readings by mail . Patients were given a st and ard procedure to follow in case of unusually high or low BP readings at home . The number and type of outpatient medical services used were obtained from patient medical records for the study year and the prior year . Costs of care for hypertension were calculated by assigning relative value units to each outpatient service . Trained technicians measured each patient 's BP at entry into the study and 1 year later . Home BP patients made 1.2 fewer hypertension-related office visits than UC patients during the study year ( 95 % confidence interval ( CI ) : 0.8,1.7 ) . Mean adjusted cost for physician visits , telephone calls , and laboratory tests associated with hypertension care was $ 88.76 per patient per year in the Home BP group , 29 % less than in the UC group ( 95 % CI : $ 16.11 , $ 54.74 ) . The annualized cost of implementing the home BP system was approximately $ 28 per patient during the study year and would currently be approximately $ 15 . After 1 year , BP control in men in the Home BP group was better than in men in the UC group ; BP control was equally good in women in both groups . Management of uncomplicated hypertension based on periodic home BP reports can achieve BP control with fewer physician visits , result ing in substantial cost savings OBJECTIVE : To compare the effects on office blood pressure and home blood pressure of placebo and active drug administration . DESIGN : After a 2-week wash-out period , patients with mild-to-moderate hypertension entered a 2-week single-blind placebo period and then a 4-week double-blind period . Patients were r and omly assigned to be administered either 2 mg tr and olapril once daily or its placebo in a 2:1 proportion . Office blood pressure was measured by a physician at the end of each period , using a mercury sphygmomanometer ( mean of three consecutive measurements ) . Home blood pressure was measured during the last week of each period according to st and ard procedure carefully taught to each patient by the physician . Compliance was checked by using electronic pill boxes . RESULTS : Data for 34 of the 44 patients who entered the study were eligible for analysis . Baseline systolic blood pressure/diastolic blood pressure were significantly ( P = 0.0001/P = 0.0001 ) higher for office blood pressure ( 161/101 mmHg ) than they were for home blood pressure ( 145/93 mmHg ) . There was no statistically significant difference between the placebo and active-treatment groups at baseline . During the single-blind period , blood pressures measured at the office and at home did not change significantly . Office blood pressure decreased by 2.7 + /- 10 mmHg for systolic blood pressure and by 0.5 + /- 4 mmHg for diastolic blood pressure whereas home blood pressure increased by 0.8 + /- 6 mmHg for systolic blood pressure and by 0.7 + /- 4 mmHg for diastolic blood pressure . During the double-blind period , office blood pressure fell significantly with tr and olapril treatment ( systolic by 10.2 + /- 12 mmHg , diastolic by 8.3 + /- 6 mmHg ; P = 0.0005/0.0001 , versus single-blind placebo period ) but this decrease was not significantly different ( P = 0.45/0.92 ) from the fall in members of the placebo group ( systolic by 6.9 + /- 9 mmHg , diastolic by 8.0 + /-6 mmHg ; P = 0.04/0.002 , versus single-blind placebo period ) . Thus , no antihypertensive effect of tr and olapril was demonstrated . The fall lin home blood pressure with tr and olapril treatment was significant ( systolic by 10.7 + /- 8 mmHg , diastolic by 5.8 + /- 5 mmHg ; both P = 0.0001 , versus single-blind placebo period ) and was significantly greater ( P = 0.0004/0.004 ) than the minimal change observed with placebo ( systolic fell by 0.2 + /- 5mmHg , diastolic fell by 0.6 + /- 4 mmHg ; P = 0.90/0.62 , respectively , versus single-blind placebo period ) . The evening decrease in home blood pressure was similar to the morning decrease in home blood pressure in members of the tr and olapril-treated group . The result ing morning : evening decrease in blood pressure ratio was 0.83 for diastolic blood pressure and 0.95 for systolic blood pressure . For the subgroup of responders , mean of individual ratios was 0.77 + /- 0.43 for diastolic blood pressure and 0.70 + /- 0.39 for systolic blood pressure . CONCLUSION : The placebo effect observed with office blood pressure measurements does not occur with home blood pressure measurements . Expected treatment effect can alter a physician 's blood pressure readings . The precision of measurements is greater with home blood pressure ( there is a lower SD ) . Use of home blood pressure measurements increases the power of comparative trials , allowing one either to study fewer subjects or to detect a smaller difference in blood pressure We evaluated time-related blood pressure trends in the Tecumseh study participants , none of whom received antihypertensive treatment . At baseline the blood pressures were measured in the field clinic and by self measurement at home ( twice daily for 7 days ) . After a mean of 3.2 + /- 0.42 years , the clinic and home pressure readings were repeated . Nine hundred forty-six subjects had clinic and home blood pressure readings at baseline . Of these 735 ( 380 men , 355 women ; average age , 32 years ) also completed the second examination . Blood pressure , morphometric data , and biochemical measures at the first examination were used as predictors of future clinic blood pressures . Five hundred ninety-six subjects were normotensive on both examinations ( 81 % ) . Of 79 subjects ( 10.7 % ) with clinic hypertension ( > 140 mg Hg systolic or 90 mm Hg diastolic ) at baseline , 38 remained hypertensive ( " sustained hypertension " ) and 41 became normotensive ( " transient hypertension " ) after 3 years . Another 60 normotensives at baseline ( 10.4 % ) became hypertensive on second examination ( " de novo hypertensives " ; incidence ; 8.1 % ) . The home blood pressure readings on both examinations were reproducible . The three hypertensive groups had elevated home blood pressure , were overweight , had dyslipidemia , and higher insulin values . Only the home blood pressure proved predictive of subsequent blood pressure trends . A home blood pressure of 128 and 83 mm Hg or higher detected " sustained " hypertension with a 48 % sensitivity and 93 % specificity . Readings of 120 and 80 mm Hg or lower predicted future normotension with a 45 % sensitivity and a 91 % specificity . We conclude that self determination of the blood pressure at home is useful in the management of borderline hypertension . An algorithm for the management of these patients is proposed OBJECTIVE To determine whether home blood pressure monitoring ( HBPM ) led to physician-initiated medication titration and improved achievement of target BP levels compared with st and ard , office-based management . METHODS Physicians were r and omly assigned to a treatment group or a control group . Patients in the control group were monitored by their physician and were drug-adjusted according to the usual approach . In the treatment group , patients were given home BP monitors ( UA-767P [ A&D Medical/Life source , USA ] ) , and drug dosing was adjusted according to HBPM readings and protocol . Long-acting diltiazem ( 240 mg/day ) was added at baseline , which was adjusted as necessary ( other medications were added if more than 360 mg/day of diltiazem was required ) . A final BP measurement was taken in the office after six weeks . RESULTS Nineteen physicians were r and omly assigned to the office BP monitoring group and 34 were assigned to the HBPM group . Of the 270 subjects recruited , 97 were in the office BP monitoring group and 173 were in the HBPM group . From baseline to the final visit , there was a statistically significant time by group interaction with lower BP in the HBPM group ( P=0.034 for both systolic BP and diastolic BP ) . BP fell from 159/91+/-11/10 mmHg at baseline in the HBPM group to 138/80+/-13/8 mmHg on the final visit , and from 160/88+/-14/10 mmHg to 141/78+/-10/9 mmHg in the control group . CONCLUSIONS BP was lowered significantly in both groups , and to a statistically greater degree in the HBPM group . The Hawthorne effect might have led to altered care by the physicians with improvement in BP control in both groups BACKGROUND The purpose of this study was to compare home and ambulatory blood pressure ( BP ) in the adjustment of antihypertensive treatment . METHODS After a 4-week washout period , patients whose untreated daytime diastolic ambulatory BP averaged > or = 85 mm Hg were r and omized to be treated according to their ambulatory or home BP . Antihypertensive treatment was adjusted at 6-week intervals according to the mean daytime ambulatory diastolic BP or the mean home diastolic BP , depending on the patient 's r and omization group . If the diastolic BP stayed above 80 mm Hg , the physician blinded to r and omization intensified hypertensive treatment . RESULTS Ninety-eight patients completed the study . During the 24-week follow-up period both systolic and diastolic BP decreased significantly within both groups ( P < .001 ) . At the end of the study , the systolic/diastolic differences between ambulatory ( n = 46 ) and home ( n = 52 ) BP groups in home , daytime ambulatory , night-time ambulatory , and 24-h ambulatory BP changes averaged 2.6/2.6 mm Hg , 0.6/1.7 mm Hg , 1.0/1.4 mm Hg , and 0.6/1.5 mm Hg , respectively ( P range .06 to .75 ) A nonsignificant trend to more intensive drug therapy in the ambulatory BP group and a nonsignificant trend to larger share of patients reaching ( 57.7 % v 43.5 % , P = .16 ) the target pressure in the home BP group was observed due to the 3.8 mm Hg difference in ambulatory and home diastolic BP at r and omization . CONCLUSIONS The adjustment of antihypertensive treatment based on either ambulatory or home BP measurement led to good BP control . No significant between-group differences in BP changes were seen at the end of the study . Additional research is needed to provide more conclusive results Objective To evaluate whether patient‐measured home blood pressures alone can be used to manage hypertension in adults 65 years and older . Methods 40 hypertensive men and women , average age 73 ± 6 years , were r and omly assigned to one of two treatment decision groups . The ‘ home ’ group ( N = 20 ) had blood pressure managed and medication changed according to measurements taken by the patient at home with the Omron HEM‐702 semi‐automatic oscillometric digital blood pressure monitor and the ‘ clinic ’ group ( N = 20 ) had medication adjusted based upon readings taken by the project nurse in the clinic . In both groups , treated hypertensives had medications adjusted downward , while untreated hypertensives were started on a diuretic and /or ACE inhibitor and adjustments were made upward . To assess the efficacy of the home measurements as a means of hypertension management , 24‐hour ambulatory blood pressure averages , quality of life ( From the QOL SF‐36 ) , and dosage of antihypertensive medications were compared between the home and clinic groups over a three‐month period . Results At baseline , the ‘ home ’ group had slightly higher ambulatory awake and sleep blood pressure than the ‘ clinic ’ group . At 3 months , the average awake and sleep ambulatory blood pressure for the ‘ home ’ group decreased to the level of the ‘ clinic ’ group . Values of the ‘ clinic ’ group did not change . In both groups , pressures of previously treated patients increased over the 3 months , while those that were previously untreated declined . However , this difference , to some extent , might be expected because the acceptable limit of pressure control ( 150 / 90 mmHg ) was higher than many of the patients on medications ; thus , their pressures could increase and still be considered controlled . Those patients who were previously untreated had their pressures decreased only to this level . The nurse‐measured clinic blood pressures for the ‘ home ’ group began higher than that of the ‘ clinic ’ group and remained higher at the end of the study . Average home pressures of the ‘ home ’ group were consistently lower than nurse‐measured clinic pressures over the 3‐month study period , indicating a persistent ‘ white coat ’ effect . Both groups had similar changes in total quality of life scores . Decrease/discontinuance of antihypertensive medication was also achieved equally in both groups at the end of 3 months . Conclusion Home blood pressure monitoring alone may be as useful as clinic measurements for making treatment decisions in the elderly Objective To investigate the usefulness of home blood pressure measurements in comparison with ambulatory monitoring in the diagnosis of sustained , white-coat hypertension and masked hypertension in children and adolescents . Subjects and methods One hundred and two subjects , referred for elevated blood pressure , were assessed with clinic ( two visits ) , home ( 6 days ) and awake ambulatory blood pressure measurements [ 64 boys , mean age 12.8 ± 2.9 ( SD ) years , range 6–18 years ] . Results Office hypertension was diagnosed in 38 subjects , ambulatory hypertension in 31 and home hypertension in 23 ( P = 0.07 ) . On the basis of clinic and ambulatory blood pressure , 52 % of subjects were normotensive , 20 % hypertensive , 18 % had white-coat hypertension and 11 % masked hypertension , whereas on the basis of clinic and home blood pressure , 55 , 15 , 23 and 8 % , respectively . There was an agreement between ambulatory and home blood pressure in the diagnosis of hypertension in 82 cases ( 80 % ) . When a 5-mmHg gray zone of diagnostic uncertainty was applied above and below the diagnostic thresholds , there were only eight cases with clinical ly important disagreement . By taking ambulatory blood pressure as the reference method for the diagnosis of hypertension , the sensitivity , specificity and positive and negative predictive values of home blood pressure were 55 , 92 , 74 and 82 % , respectively , for the diagnosis of white-coat hypertension 89 , 92 , 70 and 98 % , respectively , and for masked hypertension 36 , 96 , 50 and 93 % , respectively . Conclusion In children and adolescents , there is a reasonable agreement between home and ambulatory blood pressure measurements as diagnostic methods in hypertension . Home blood pressure appears to be a useful diagnostic test in this population , particularly for the detection of white-coat hypertension Objective To provide a direct comparison of the trough : peak ratio ( TPR ) , the morning : evening home blood pressure ratio ( MER ) and the smoothness index ( SI ) in assessing the features of the antihypertensive drug effect . Patients and methods A total of 27 untreated hypertensives were r and omized to receive lisinopril 20 mg o.d . or losartan 50 mg o.d . for 5 weeks and were subsequently crossed-over to the alternative treatment for a second 5-week period . Twenty-four hour ambulatory and 5-day home blood pressure were monitored before r and omization and at the end of each treatment period . TPR , MER and SI were calculated for each drug for the total study population and for responders only . Results When all patients were considered , lisinopril provided higher values of TPR [ 0.63/0.66 for systolic/diastolic blood pressure ( SBP/DBP ) ] , MER ( 1.02/0.77 ) and SI ( 1.01/0.87 ) than losartan ( 0.35/0.51 , 0.60/0.60 and 0.64/0.53 , respectively ) . Analysis of responders only , again showed a clear advantage of lisinopril over losartan in TPR ( 0.77/0.67 versus 0.44/0.47 , respectively ) and MER ( 0.86/0.87 versus 0.48/0.61 ) , whereas there was no difference in SI ( 1.25/1.13 for lisinopril versus 1.11/1.12 for losartan ) . Conclusions These data suggest that the assessment of the duration of the antihypertensive drug effect provided by the MER is consistent to that by the TPR and that two drugs with different levels of TPR and MER may have the same level of SI . It appears that the SI is not simply a more reliable index of the features of the antihypertensive drug effect , but offers a different type of information complementary to that provided by the TPR and the MER , in regard to the homogeneity and the magnitude but not the duration of the antihypertensive effect Objective To evaluate the efficacy of a programme of home blood pressure measurement ( HBPM ) on therapeutic compliance in mild-to-moderate hypertension . Design A prospect i ve controlled multicentre clinical trial . Setting Forty primary care centres in Spain , with a duration of 6 months . Patients A total of 250 patients with newly diagnosed or uncontrolled hypertension were included . Interventions The patients were r and omly selected and distributed in two groups : ( 1 ) the control group ( CG ) who received st and ard health intervention ; ( 2 ) the intervention group ( IG ) : the patients in this group received an OMRON in their homes for a programme of HBPM . Main outcome measure Four visits were scheduled , for the measurement of blood pressure ( BP ) . They were provided with an electronic monitor for measuring compliance ( monitoring events medication system ; MEMS ) . Therapeutic compliance was defined as a drug consumption of 80–110 % . A number of variables were calculated using the MEMS . The mean BP were calculated and the percentage of controlled patients . Results A total of 200 patients completed the study ( 100 in each group ) . Compliance was observed in 74 and 92 % , respectively , in the CG and IG [ 95 % confidence interval ( CI ) 63.9–84.1 and 86.7–97.3 ; P = 0.0001 ] , the mean percentage compliances were 87.6 and 93.5 % ( 95 % CI 81.2–94 and 80.7–98.3 ; P = 0.0001 ) , the percentages of correct days were 83.6 and 89.4 % , the percentages of subjects who took the medication at the prescribed time were 79.89 and 88.06 % , and the levels of therapeutic cover were 86.7 and 93.1 % . The number needed to treat to avoid one case of non-compliance was 5.6 patients . The differences in the mean decreases in BP were significant for diastolic BP , with a greater decrease observed in the IG . Conclusions An HBPM programme using electronic monitors is effective in improving compliance in arterial hypertension , measured using the MEMS Abstract Objectives To assess whether blood pressure control in primary care could be improved with the use of patient held targets and self monitoring in a practice setting , and to assess the impact of these on health behaviours , anxiety , prescribed antihypertensive drugs , patients ' preferences , and costs . Design R and omised controlled trial . Setting Eight general practice s in south Birmingham . Participants 441 people receiving treatment in primary care for hypertension but not controlled below the target of < 140/85 mm Hg . Interventions Patients in the intervention group received treatment targets along with facilities to measure their own blood pressure at their general practice ; they were also asked to visit their general practitioner or practice nurse if their blood pressure was repeatedly above the target level . Patients in the control group received usual care ( blood pressure monitoring by their practice ) . Main outcome measures Primary outcome : change in systolic blood pressure at six months and one year in both intervention and control groups . Secondary outcomes : change in health behaviours , anxiety , prescribed antihypertensive drugs , patients ' preferences of method of blood pressure monitoring , and costs . Results 400 ( 91 % ) patients attended follow up at one year . Systolic blood pressure in the intervention group had significantly reduced after six months ( mean difference 4.3 mm Hg ( 95 % confidence interval 0.8 mm Hg to 7.9 mm Hg ) ) but not after one year ( mean difference 2.7 mm Hg ( – 1.2 mm Hg to 6.6 mm Hg ) ) . No overall difference was found in diastolic blood pressure , anxiety , health behaviours , or number of prescribed drugs . Patients who self monitored lost more weight than controls ( as evidence d by a drop in body mass index ) , rated self monitoring above monitoring by a doctor or nurse , and consulted less often . Overall , self monitoring did not cost significantly more than usual care ( £ 251 ( $ 437 ; 364 euros ) ( 95 % confidence interval £ 233 to £ 275 ) versus £ 240 ( £ 217 to £ 263 ) . Conclusions Practice based self monitoring result ed in small but significant improvements of blood pressure at six months , which were not sustained after a year . Self monitoring was well received by patients , anxiety did not increase , and there was no appreciable additional cost . Practice based self monitoring is feasible and results in blood pressure control that is similar to that in usual care Objective There is evidence that home blood pressure ( BP ) is being used in clinical practice for the assessment of out-of-office blood pressure in children . However , there is no information on the normal range of home BP in this population . This prospect i ve school-based study was design ed to investigate the normal range of home BP in children and adolescents . Subjects and methods A total of 778 healthy subjects ( 358 boys ) with mean age 12.3 ± 3.3 ( SD ) years ( range 6–18 years ) , height 157 ± 18 cm ( 113–198 cm ) and weight 50 ± 18 kg ( 16–135 kg ) were included . Home BP was monitored for 3 days using vali date d electronic devices ( Omron 705IT ) . Results Reliable home BP readings provided by 767 subjects ( 98 % ) were analysed . Strong correlations were found between systolic home BP and body height ( r = 0.49 ) and age ( r = 0.41 ) , whereas for diastolic BP these correlations were poor ( r = 0.11 and 0.08 , respectively ) . The 50th ( midpoint of distribution ) and the 95th percentile ( suggested upper normal limit ) for systolic and diastolic home BP in children are provided by body height . There was a marked increase in the estimated 95th percentile for systolic home BP with increasing height in boys ( from 119 to 134 mmHg ) and less so in girls ( from 119 to 128 cm ) . Regarding diastolic home BP , there was little change with increasing height ( from 75 to 80 cm ) and no difference between boys and girls . Conclusions These data suggest that home BP monitoring in children and adolescents is feasible . Reference values for home BP in the paediatric population are provided Home blood pressure monitoring ( HBPM ) overcomes many of the limitations of traditional office blood pressure ( BP ) measurement and is both cheaper and easier to perform than ambulatory BP monitoring . Monitors that use the oscillometric method are currently available that are accurate , reliable , easy to use , and relatively inexpensive . An increasing number of patients are using them regularly to check their BP at home , but although this has been endorsed by national and international guidelines , detailed recommendations for their use have been lacking . There is a rapidly growing literature showing that measurements taken by patients at home are often lower than readings taken in the office and closer to the average BP recorded by 24-hour ambulatory monitors , which is the BP that best predicts cardiovascular risk . Because of the larger numbers of readings that can be taken by HBPM than in the office and the elimination of the white-coat effect ( the increase of BP during an office visit ) , home readings are more reproducible than office readings and show better correlations with measures of target organ damage . In addition , prospect i ve studies that have used multiple home readings to express the true BP have found that home BP predicts risk better than office BP ( Class IIa ; Level of Evidence A ) . This call-to-action article makes the following recommendations : ( 1 ) It is recommended that HBPM should become a routine component of BP measurement in the majority of patients with known or suspected hypertension ; ( 2 ) Patients should be advised to purchase oscillometric monitors that measure BP on the upper arm with an appropriate cuff size and that have been shown to be accurate according to st and ard international protocol s. They should be shown how to use them by their healthcare providers ; ( 3 ) Two to 3 readings should be taken while the subject is resting in the seated position , both in the morning and at night , over a period of 1 week . A total of ≥12 readings are recommended for making clinical decisions ; ( 4 ) HBPM is indicated in patients with newly diagnosed or suspected hypertension , in whom it may distinguish between white-coat and sustained hypertension . If the results are equivocal , ambulatory BP monitoring may help to establish the diagnosis ; ( 5 ) In patients with prehypertension , HBPM may be useful for detecting masked hypertension ; ( 6 ) HBPM is recommended for evaluating the response to any type of antihypertensive treatment and may improve adherence ; ( 7 ) The target HBPM goal for treatment is < 135/85 mm Hg or < 130/80 mm Hg in high-risk patients ; ( 8) HBPM is useful in the elderly , in whom both BP variability and the white-coat effect are increased ; ( 9 ) HBPM is of value in patients with diabetes , in whom tight BP control is of paramount importance ; ( 10 ) Other population s in whom HBPM may be beneficial include pregnant women , children , and patients with kidney disease ; and ( 11 ) HBPM has the potential to improve the quality of care while reducing costs and should be reimbursed CONTEXT Treating hypertension decreases mortality and disability from cardiovascular disease , but most hypertension remains inadequately controlled . OBJECTIVE To determine if a new model of care that uses patient Web services , home blood pressure ( BP ) monitoring , and pharmacist-assisted care improves BP control . DESIGN , SETTING , AND PARTICIPANTS A 3-group r and omized controlled trial , the Electronic Communications and Home Blood Pressure Monitoring study was based on the Chronic Care Model . The trial was conducted at an integrated group practice in Washington state , enrolling 778 participants aged 25 to 75 years with uncontrolled essential hypertension and Internet access . Care was delivered over a secure patient Web site from June 2005 to December 2007 . INTERVENTIONS Participants were r and omly assigned to usual care , home BP monitoring and secure patient Web site training only , or home BP monitoring and secure patient Web site training plus pharmacist care management delivered through Web communications . MAIN OUTCOME MEASURES Percentage of patients with controlled BP ( < 140/90 mm Hg ) and changes in systolic and diastolic BP at 12 months . RESULTS Of 778 patients , 730 ( 94 % ) completed the 1-year follow-up visit . Patients assigned to the home BP monitoring and Web training only group had a nonsignificant increase in the percentage of patients with controlled BP ( < 140/90 mm Hg ) compared with usual care ( 36 % [ 95 % confidence interval { CI } , 30%-42 % ] vs 31 % [ 95 % CI , 25%-37 % ] ; P = .21 ) . Adding Web-based pharmacist care to home BP monitoring and Web training significantly increased the percentage of patients with controlled BP ( 56 % ; 95 % CI , 49%-62 % ) compared with usual care ( P < .001 ) and home BP monitoring and Web training only ( P < .001 ) . Systolic BP was decreased stepwise from usual care to home BP monitoring and Web training only to home BP monitoring and Web training plus pharmacist care . Diastolic BP was decreased only in the pharmacist care group compared with both the usual care and home BP monitoring and Web training only groups . Compared with usual care , the patients who had baseline systolic BP of 160 mm Hg or higher and received home BP monitoring and Web training plus pharmacist care had a greater net reduction in systolic BP ( -13.2 mm Hg [ 95 % CI , -19.2 to -7.1 ] ; P < .001 ) and diastolic BP ( -4.6 mm Hg [ 95 % CI , -8.0 to -1.2 ] ; P < .001 ) , and improved BP control ( relative risk , 3.32 [ 95 % CI , 1.86 to 5.94 ] ; P<.001 ) . CONCLUSION Pharmacist care management delivered through secure patient Web communications improved BP control in patients with hypertension . Trial Registration clinical trials.gov Identifier : NCT00158639 BACKGROUND The Take Control of Your Blood Pressure trial evaluated the effect of a multicomponent telephonic behavioral lifestyle intervention , patient self-monitoring , and both interventions combined compared with usual care on reducing systolic blood pressure during 24 months . The combined intervention led to a significant reduction in systolic blood pressure compared with usual care alone . We examined direct and patient time costs associated with each intervention . METHODS We conducted a prospect i ve economic evaluation alongside a r and omized controlled trial of 636 patients with hypertension participating in the study interventions . Medical costs were estimated using electronic data representing medical services delivered within the health system . Intervention-related costs were derived using information collected during the trial , administrative records , and published unit costs . RESULTS During 24 months , patients incurred a mean of $ 6,965 ( s.d . , $ 22,054 ) in inpatient costs and $ 8,676 ( s.d . , $ 9,368 ) in outpatient costs , with no significant differences among the intervention groups . With base-case assumptions , intervention costs were estimated at $ 90 ( s.d . , $ 2 ) for home blood pressure monitoring , $ 345 ( s.d . , $ 64 ) for the behavioral intervention ( $ 31 per telephone encounter ) , and $ 416 ( s.d . , $ 93 ) for the combined intervention . Patient time costs were estimated at $ 585 ( s.d . , $ 487 ) for home monitoring , $ 55 ( s.d . , $ 16 ) for the behavioral intervention , and $ 741 ( s.d . , $ 529 ) for the combined intervention . CONCLUSIONS Our analysis demonstrated that the interventions are cost-additive to the health-care system in the short term and that patients ' time costs are nontrivial |
1,250 | 22,986,379 | Statistically significant effects were mostly found in reducing hospital use ( for example , rehospitalizations ) , improvement of continuity of care ( for example , accurate discharge information ) , and improvement of patient status after discharge ( for example , satisfaction ) .
Many interventions have positive effects on patient care .
However , given the complexity of interventions and outcome measures , the literature does not permit firm conclusions about which interventions have these effects . | BACKGROUND Evidence shows that suboptimum h and overs at hospital discharge lead to increased rehospitalizations and decreased quality of health care .
PURPOSE To systematic ally review interventions that aim to improve patient discharge from hospital to primary care . | Objective Heart failure patients are regularly admitted to hospital and frequently use multiple medication . Besides intentional changes in pharmacotherapy , unintentional changes may occur during hospitalisation . The aim of this study was to investigate the effect of a clinical pharmacist discharge service on medication discrepancies and prescription errors in patients with heart failure . Setting A general teaching hospital in Tilburg , the Netherl and s. Method An open r and omized intervention study was performed comparing an intervention group , with a control group receiving regular care by doctors and nurses . The clinical pharmacist discharge service consisted of review of discharge medication , communicating prescribing errors with the cardiologist , giving patients information , preparation of a written overview of the discharge medication and communication to both the community pharmacist and the general practitioner about this medication . Within 6 weeks after discharge all patients were routinely scheduled to visit the outpatient clinic and medication discrepancies were measured . Main outcome measure The primary endpoint was the frequency of prescription errors in the discharge medication and medication discrepancies after discharge combined . Results Forty-four patients were included in the control group and 41 in the intervention group . Sixty-eight percent of patients in the control group had at least one discrepancy or prescription error against 39 % in the intervention group ( RR 0.57 ( 95 % CI 0.37–0.88 ) ) . The percentage of medications with a discrepancy or prescription error in the control group was 14.6 % and in the intervention group it was 6.1 % ( RR 0.42 ( 95 % CI 0.27–0.66 ) ) . Conclusion This clinical pharmacist discharge service significantly reduces the risk of discrepancies and prescription errors in medication of patients with heart failure in the 1st month after discharge OBJECTIVES to investigate the effectiveness of a pharmacy discharge plan in elderly hospitalized patients . DESIGN r and omized controlled trial . SUBJECTS AND SETTING S we r and omized patients aged 75 years and older on four or more medicines who had been discharged from three acute general and one long-stay hospital to a pharmacy intervention or usual care . INTERVENTIONS the hospital pharmacist developed discharge plans which gave details of medication and support required by the patient . A copy was given to the patient and to all relevant professionals and carers . This was followed by a domiciliary assessment by a community pharmacist . In the control group , patients were discharged from hospital following st and ard procedures that included a discharge letter to the general practitioner listing current medications . OUTCOMES the primary outcome was re-admission to hospital within 6 months . Secondary outcomes included the number of deaths , attendance at hospital outpatient clinics and general practice and proportion of days in hospital over the follow-up period , together with patients ' general well-being , satisfaction with the service and knowledge of and adherence to prescribed medication . RESULTS we recruited 362 patients , of whom 181 were r and omized to each group . We collected hospital and general practice data on at least 91 and 72 % of patients respectively at each follow-up point and interviewed between 43 and 90 % of the study subjects . There were no significant differences between the groups in the proportion of patients re-admitted to hospital between baseline and 3 months or 3 and 6 months . There were no significant differences in any of the secondary outcomes . CONCLUSIONS we found no evidence to suggest that the co-ordinated hospital and community pharmacy care discharge plans in elderly patients in this study influence outcomes BACKGROUND Hospitalization and subsequent discharge home often involve discontinuity of care , multiple changes in medication regimens , and inadequate patient education , which can lead to adverse drug events ( ADEs ) and avoidable health care utilization . Our objectives were to identify drug-related problems during and after hospitalization and to determine the effect of patient counseling and follow-up by pharmacists on preventable ADEs . METHODS We conducted a r and omized trial of 178 patients being discharged home from the general medicine service at a large teaching hospital . Patients in the intervention group received pharmacist counseling at discharge and a follow-up telephone call 3 to 5 days later . Interventions focused on clarifying medication regimens ; review ing indications , directions , and potential side effects of medications ; screening for barriers to adherence and early side effects ; and providing patient counseling and /or physician feedback when appropriate . The primary outcome was rate of preventable ADEs . RESULTS Pharmacists observed the following drug-related problems in the intervention group : unexplained discrepancies between patients ' preadmission medication regimens and discharge medication orders in 49 % of patients , unexplained discrepancies between discharge medication lists and postdischarge regimens in 29 % of patients , and medication nonadherence in 23 % . Comparing trial outcomes 30 days after discharge , preventable ADEs were detected in 11 % of patients in the control group and 1 % of patients in the intervention group ( P = .01 ) . No differences were found between groups in total ADEs or total health care utilization . CONCLUSIONS Pharmacist medication review , patient counseling , and telephone follow-up were associated with a lower rate of preventable ADEs 30 days after hospital discharge . Medication discrepancies before and after discharge were common targets of intervention Context Research on patient safety has focused on adverse events in hospitalized patients . Adverse events following hospitalization have received little attention . Contribution Among 400 consecutive patients discharged from the general medical service of an academic hospital , 76 had adverse events during the 2 weeks following hospital discharge . Of the adverse events , the research ers categorized 23 as preventable , 24 as ameliorable , and the remainder as neither . Adverse drug events were the most frequent occurrence . Implication s Interventions to maximize patient safety should consider the vulnerable transition from hospital to home . The Editors Patient safety is a public concern that has received substantial attention , especially since the release of two reports from the U.S. Institute of Medicine . The first of these , To Err Is Human , review ed the literature on adverse events , or injuries result ing from medical care ( 1 ) . On the basis of data from two large population -based chart review studies , the report estimated that adverse events occur in 2.9 % ( 2 ) to 3.7 % ( 3 ) of hospitalizations . The first of these studies ( 2 ) found that although most injuries are minor , approximately 1 in 10 results in death . The research ers determined that approximately half of the adverse events were caused by errors ( 1 , 3 , 4 ) . The second report , Crossing the Quality Chasm , which proposes strategies for improving the health system , declared patient safety a fundamental component of care quality ( 5 ) . However , the estimated incidence of adverse events quoted in To Err Is Human may underestimate the overall safety problem , since injuries occurring after discharge were not included in the evaluation . Patients may be especially vulnerable to injuries during this period because they may still have functional impairments and because discontinuities may occur at the interface of acute and ambulatory care ( 6 ) . These discontinuities may be worsened by the current health care environment , in which patients are leaving the hospital quicker and sicker ( 7 ) and may receive care from hospitalists rather than their primary care physicians ( 8) . Despite these theoretical concerns , few studies are available to estimate the extent of the problem . Several studies have determined the risk for postdischarge wound infections in surgical patients ( 9 , 10 ) , but this is a specific type of safety problem and the risk can not be generalized . Other studies have used readmission rates to identify poor- quality hospital care ( 11 ) . However , this outcome is an insensitive and nonspecific marker of quality in general ( 11 ) and safety in particular . Information on the incidence and type of adverse events is vital for improving postdischarge safety . We wanted to determine the incidence and severity of adverse events affecting patients after discharge from the hospital to home . In addition , we wanted to identify the incidence of preventable and ameliorable adverse events , classify types of adverse events , and identify system improvements to reduce the incidence and severity of adverse events after discharge . Methods Overview To determine the rate of adverse events , we first created a case summary of every patient 's posthospital course by performing a medical record review and a telephone interview approximately 3 weeks after discharge . Using this information , we created event summaries , which two board-certified internists independently review ed to determine whether medical management caused an injury and , if so , whether it was preventable or ameliorable . The institutional review board at the study hospital approved the protocol . Definitions Adverse outcomes were any of the following patient experiences after discharge : new or worsening symptoms , unanticipated visits to health facilities for tests or treatments , or death . An adverse event was an injury result ing from medical management rather than the underlying disease . We evaluated all injuries result ing in symptoms after discharge , regardless of when the events occurred . Thus , we included adverse events that occurred in the hospital and after discharge as long as symptoms persisted until the patient went home . A preventable adverse event was an injury that could have been avoided , that is , an injury judged to probably be the result of an error or a system design flaw . An ameliorable adverse event was an injury whose severity could have been substantially reduced if different actions or procedures had been performed or followed . Patient Sample We used a prospect i ve cohort design to study adult medical patients at an 800-bed urban academic teaching hospital . Patients were included if they went home from the general medical service during a sequential 81-day period , had telephone service , and could complete a telephone interview in English . Patient surrogates were permitted to complete the interview if the patient could not . Telephone Interview A board-certified internist contacted patients by telephone within 2 to 5 weeks of discharge . If the patient was eligible and consented , he or she underwent a semi-structured interview over the telephone . If the patient was not available , we made up to 20 attempts to contact him or her at different times of the day and week . If the patient declined to participate or we were unable to contact him or her after 5 weeks , we rated the patient as a nonresponder . Responders underwent a telephone interview that had several components ( Appendix Figure ) . The principal component assessed the patient 's condition since discharge by using a full review of organ systems . If patients answered yes to any question , the interviewer asked them to elaborate about the symptom 's severity , timing in relation to hospitalization and treatments , and resolution . The survey also determined patients ' use of health services since discharge , including home care services , physician services , visits to laboratories , and readmissions to the hospital . Preparation of Case Summaries To create a case summary , the internist combined the information from the telephone interview with information obtained from a review of the patient 's electronic medical record . This computerized clinical record contains h and over notes from the hospitalization ; discharge summaries ; previous orders and written instructions ; emergency department and clinic notes ; operative and procedure notes ; and all laboratory results , including results of radiography , electrocardiography , and pathologic examination . If necessary , the paper chart was also review ed to clarify information that was in the discharge summary or h and over notes . If patients returned to the study hospital after discharge , we were able to vali date their history by review ing their records . However , for patients receiving care elsewhere , we had to rely on firsth and accounts . Preparation of Event Summaries The internist review ed every patient 's case summary for adverse outcomes . If any were found , an event summary that consisted of a detailed description of each outcome , including its onset , its severity , the health services used during its treatment , and its resolution , was created for each one . If there were no adverse outcomes , then the event summary consisted of the case summary . Determination of Adverse Events Two other board-certified internists independently rated each event summary by using st and ard techniques as described elsewhere ( 3 ) . Each event summary was evaluated separately . Review ers first rated on a scale of 1 to 6 their confidence that medical management caused an injury . If their rating was 5 or 6 , indicating that the injury was probably or definitely caused by management , the event was considered an adverse event . For adverse events , the internists used implicit criteria to determine their preventability and ameliorability . The two review ers ' assessment s were then compared for causality , preventability , and ameliorability . If there was disagreement , the two review ers discussed the case to attempt to come to consensus . If they did not agree , a third board-certified internist rated the event independently . Next , review ers rated injury severity , health services used , type of injury , and location . Injury severity was categorized as serious laboratory abnormality only , one day of symptoms , several days of symptoms , nonpermanent disability , permanent disability , or death . Differentiation between several days of symptoms and nonpermanent disability relied on evidence that symptoms interfered with patients ' activities of daily living . We categorized health services used as none , additional visit to a physician , additional visit for laboratory testing in addition to a physician visit , visit to an emergency department , readmission to the hospital , or death . We were able to determine whether health services were additional because during the interview we asked whether the health service was arranged before discharge or specifically for the particular symptom . We used a st and ard approach to classify the type of injury ( 2 , 3 ) , categorizing each as an adverse drug event , a procedure-related injury , a nosocomial infection , a fall , or other . We also classified the location of adverse events . Our primary objective was to evaluate adverse events affecting patients after discharge from the hospital to home . We felt that most of these events would occur after the patient went home , but we recognized a priori that some adverse events could occur in the hospital but lead to morbidity after discharge because of the severity of the injury or because health providers did not recognize the problem at discharge . Examples of injuries occurring in the hospital but affecting patients after discharge include pressure ulcers , missed diagnoses , and erroneous drug prescriptions . If it was determined that the adverse event occurred in the hospital , we examined whether the injury was recognized before discharge and , if so , whether definitive management was instituted at that time . To develop strategies UNLABELLED The purpose of this paper is to identify the information that nurses in hospitals exchange with nurses in home health care ( HHC ) , and what nurses perceive to be the most significant information to exchange . METHOD Nurses have an obligation to support and ensure continuity of patient care and to prevent an information gap when patients are transferred from one organizational of health care delivery to another organizational level , for example , from hospital to home health care . In an ongoing prospect i ve study , nurses ' pre-electronic nursing discharge note and their assessment of the information it was necessary to exchange at the same time was audited and analyzed . The results show variation in the completeness and content of the nursing discharge note . Nurses ' underst and ing of the scope and content of information to be transmitted varies widely according to the context and the organizational health care level they work within . The implementation of an electronic nursing discharge note creates the opportunity to identify the accurate information elements that must be documented and exchanged between the nurses to ensure patient safety and inter-organizational continuity of care OBJECTIVE To determine the impact of a hospital-coordinated discharge care plan , involving a multidisciplinary team of primary health care providers , on hospital length of stay , quality of life , and both patient and general practitioner inclusion in , and satisfaction with , discharge procedures . DESIGN This investigation comprised a prospect i ve , r and omized , controlled , clinical trial . SETTING This multicentre and cross-jurisdictional study focused on areas of tertiary and primary health care as well as community allied health in Western Australia . PARTICIPANTS Patients ( n = 189 ) with chronic cardiorespiratory diagnoses were recruited from respiratory , cardiovascular , and general medical wards at two tertiary hospitals . INTERVENTION Subjects were r and omly assigned to one of two groups . Intervention group patients received a discharge care plan in accordance with that outlined in the Australian Enhanced Primary Care Package , completed before discharge and sent to the patient 's general practitioner and other community service providers for review . Control patients were discharged under existing hospital processes . Outcome measures . Patients and general practitioners were surveyed pre-discharge and 7 days post-discharge for quality of life and opinion of discharge procedures . Hospital length of stay was also determined . RESULTS Significant improvements in discharge planning involvement , health service access , confidence with discharge procedures , and opinion of discharge based on previous experience were seen for patients who received the discharge care plan . Further , improved perceptions of mental quality of life were observed within the first week post-discharge for intervention patients . Length of stay showed no difference between groups . Extent and speed of hospital-general practitioner communication were significantly improved via the intervention . CONCLUSIONS Our results indicate that a multidisciplinary discharge care plan , initiated before separation , improves quality of life , involvement , and satisfaction with discharge care , and hospital-general practitioner integration . As such , it possesses benefits over current Western Australian hospital discharge procedures for the care of chronically ill population Patients with breast cancer who require axillary clearance traditionally remain in hospital until their wound drains are removed . Early discharge has been shown to improve clinical outcomes , but there has been little assessment of the psychosocial and financial impact of early discharge on patients , carers and the health service . This study aim ed to evaluate the effectiveness of a nurse-led model of early discharge from hospital . Main outcome measures were quality of life and carer burden . Secondary outcomes included patient satisfaction , arm morbidity , impact on community nurses , health service costs , surgical cancellations and in-patient nursing dependency . A total of 108 patients undergoing axillary clearance with mastectomy or wide local excision for breast cancer were r and omised to nurse-led early discharge or conventional stay . Nurse-led early discharge had no adverse effects on quality of life or patient satisfaction , had little effect on carer burden , improved communication between primary and secondary care , reduced cancellations and was safely implemented in a mixed rural/urban setting . In total , 40 % of eligible patients agreed to take part . Non participants were significantly older , more likely to live alone and had lower emotional well being before surgery . This study provides further evidence of the benefits of early discharge from hospital following axillary clearance for breast cancer . However , if given the choice , most patients prefer to stay in hospital until their wound drains are removed PURPOSE The effect of a medication discharge plan ( MDP ) on the rate of medication discrepancies between hospital and outpatient setting s was evaluated . METHODS In a pragmatic , open , r and omized , controlled trial , MDPs were completed for all patients before discharge from the hospital . Patients were then assigned to either an MDP group , for whom MDPs were sent to community pharmacies and treating physicians , or a usual care group , for whom an MDP was not sent . Discrepancies between MDPs and community pharmacy dispensing records and medication use reported by patients during a telephone interview were documented . The percentage of patients with discrepancies and the mean percentage of medications with discrepancies were compared between the two groups . The clinical severity of discrepancies was blindly evaluated . RESULTS A total of 83 patients agreed to participate in the study . The percentage of patients with at least one discrepancy was high and similar in both groups when MDPs were compared with pharmacy dispensing records and patient self-reports . Comparison of MDPs to pharmacy dispensing records revealed discrepancies for 13 - 15 % of medications ; more than a third were clinical ly significant . Comparison of MDPs to patient self-reports revealed discrepancies for 10 - 12 % of medications ; 48 % were clinical ly significant . No significant differences were observed between the two groups . CONCLUSION The rate of medication discrepancies was not decreased in patients whose MDP was provided to their community pharmacy and physician at the time of hospital discharge compared with the rate in patients who received usual care Systematic review s provide the best evidence on the effectiveness of healthcare interventions including quality improvement strategies . The methods of systematic review of individual patient r and omised trials of healthcare interventions are well developed . We discuss method ological and practice issues that need to be considered when undertaking systematic review s of quality improvement strategies including developing a review protocol , identifying and screening evidence sources , quality assessment and data abstract ion , analytical methods , reporting systematic review s , and appraising systematic review s. This paper builds on our experiences within the Cochrane Effective Practice and Organisation of Care ( EPOC ) review group 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 OBJECTIVE To examine the effectiveness of delivering of computer-generated discharge summaries to general practice by email , fax , post and patient h and delivery . DESIGN Blinded , r and omized controlled trial . A pre- study audit ascertaining baseline statistics and a follow-up survey were conducted with general practice to determine preferred medium for receiving discharge communication . PARTICIPANTS AND SETTING 196 geriatric patients who were admitted to the aged care ward of a 300-bed metropolitan teaching hospital . Twenty-eight patients were lost to follow-up and 52 general practice s participated in the final survey . The pre- study audit followed 63 discharges from the same ward . INTERVENTION 168 eligible patients were r and omly assigned to have their electronic discharge summary sent by email ( n=40 ) , fax ( n=48 ) , post ( n=40 ) or patient h and delivery ( n=40 ) . MAIN OUTCOME MEASURES Receipt of discharge summary by the general practice clinic within 7 days of patient discharge from hospital . RESULTS The receipt rates for email ( 73.9 % , n=17 ) and fax were comparable ( 69.4 % , n=25 ; chi(2)=0.137 , df=1 , P=0.712 ) , and significantly higher ( chi(2)=19.86 , df=3 , P<0.0002 ) than post ( 43.8 % , n=14 ) and patient h and delivery ( 24.2 % , n=8 ) . General practice s indicated that fax was the most preferred method ( 82.7 % ) for communication of discharge summaries . The majority of general practice s ( 75.0 % ) utilized an electronic system for storage of patient information while 88.5 % of practice s reported using medical prescribing software . CONCLUSIONS Transmission of computer-generated discharge summaries by fax or email offers the most effective method of communicating with primary care physicians , as long as accurate contact information is available . Although fax is still the most preferred , email has many advantages that could potentially allow it to replace fax as a st and ard mode for delivery of discharge communication BACKGROUND Medication reconciliation at transitions in care is a national patient safety goal , but its effects on important patient outcomes require further evaluation . We sought to measure the impact of an information technology-based medication reconciliation intervention on medication discrepancies with potential for harm ( potential adverse drug events [ PADEs ] ) . METHODS We performed a controlled trial , r and omized by medical team , on general medical inpatient units at 2 academic hospitals from May to June 2006 . We enrolled 322 patients admitted to 14 medical teams , for whom a medication history could be obtained before discharge . The intervention was a computerized medication reconciliation tool and process re design involving physicians , nurses , and pharmacists . The main outcome was unintentional discrepancies between preadmission medications and admission or discharge medications that had potential for harm ( PADEs ) . RESULTS Among 160 control patients , there were 230 PADEs ( 1.44 per patient ) , while among 162 intervention patients there were 170 PADEs ( 1.05 per patient ) ( adjusted relative risk [ ARR ] , 0.72 ; 95 % confidence interval [ CI ] , 0.52 - 0.99 ) . A significant benefit was found at hospital 1 ( ARR , 0.60 ; 95 % CI , 0.38 - 0.97 ) but not at hospital 2 ( ARR , 0.87 ; 95 % CI , 0.57 - 1.32 ) ( P = .32 for test of effect modification ) . Hospitals differed in the extent of integration of the medication reconciliation tool into computerized provider order entry applications at discharge . CONCLUSIONS A computerized medication reconciliation tool and process re design were associated with a decrease in unintentional medication discrepancies with potential for patient harm . Software integration issues are likely important for successful implementation of computerized medication reconciliation tools 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 Objective : To evaluate the impact of a hospital based community liaison pharmacy service on a range of outcomes in patients aged more than 55 years and taking more than 3 prescribed drugs , who had been admitted to the medical unit of a district general hospital in Northern Irel and . Methods : Having recruited 243 patients , a total of 162 patients completed the full protocol ( 81 r and omly assigned to intervention and 81 to control ; mean age of control patients 75 years ; mean age of intervention patients 73 years ) . The interventions by the community liaison pharmacist included : preparation of an accurate medication record following a full review of current medication use ; medication counselling ; provision of a medicines record sheet informing the patient how to take their drugs ; provision of a pharmaceutical discharge letter detailing changes made to drug therapy ( this was faxed to the patient 's GP and community pharmacist on the day of discharge ) ; provision of a Medicines Helpline . Results : The key findings were as follows : problems were identified in 80 % of the intervention patients ' prescription charts , 49 % of which related to drug omissions from the patients ' domiciliary prescriptions . The GP practice record was the most accurate ( mean error rate 12.6 % ) while the GP referral letter was the least accurate ( mean error rate 47.3 % ) source of medication information . Drugs patients brought to hospital were also an inaccurate source ( mean error rate 44.0 % ) . The intervention group patients , when compared with control patients , had a significant reduction ( P=0.005 ) in drug mismatch between drugs prescribed at discharge and taken at home , and had a greater knowledge of their drug regimen 10–14 days after discharge ( P |Ld 0.001 ) . The vast majority of patients ( 96 % ) felt that the provision of a medicine helpline was a useful service . Conclusions : The study indicated clear benefits from the involvement of a hospital based community liaison pharmacist in achieving seamless pharmaceutical care between the primary and secondary healthcare setting Abstract Objectives . Many hospital admissions are due to inappropriate medical treatment , and discharge of fragile elderly patients involves a high risk of readmission . The present study aim ed to assess whether a follow-up programme undertaken by GPs and district nurses could improve the quality of the medical treatment and reduce the risk of readmission of elderly newly discharged patients . Design and setting . The patients were r and omized to either an intervention group receiving a structured home visit by the GP and the district nurse one week after discharge followed by two contacts after three and eight weeks , or to a control group receiving the usual care . Patients . A total of 331 patients aged 78 + years discharged from Glostrup Hospital , Denmark , were included . Main outcome measures . Readmission rate within 26 weeks after discharge among all r and omized patients . Control of medication , evaluated 12 weeks after discharge on 293 ( 89 % ) of the patients by an interview at home and by a question naire to the GP . Results . Control-group patients were more likely to be readmitted than intervention-group patients ( 52 % v 40 % ; p = 0.03 ) . In the intervention group , the proportions of patients who used prescribed medication of which the GP was unaware ( 48 % vs. 34 % ; p = 0.02 ) and who did not take the medication prescribed by the GP ( 39 % vs. 28 % ; p = 0.05 ) were smaller than in the control group . Conclusion . The intervention shows a possible framework securing the follow-up on elderly patients after discharge by reducing the readmission risk and improving medication control OBJECTIVE We aim ed to assess whether GP input into discharge planning for high-risk aged in- patients admitted under the care of a geriatrician results in improved patient outcomes . METHODS We conducted a prospect i ve r and omized controlled trial in Sydney , Australia . The subjects were 364 patients aged 60 years and over . The main outcome measures included community service referral , accommodation changes , length of stay , readmission rate , length of time to first readmission and patient satisfaction with discharge arrangements . RESULTS No significant differences were found with regard to length of stay , readmission rates or time to first readmission . Test-group subjects were significantly more likely to be recommended for community services at discharge and to report that hospital personnel had discussed their discharge plan with them . Significantly more of the test group reported that their return home was well prepared . CONCLUSIONS Although GP pre-discharge visits did not alter the likelihood of ' hard outcomes such as risk of readmission ' , the results suggest that quality of care is enhanced amongst patients receiving a pre-discharge visit and that GPs can perform a key role in planning post-discharge care with other services OBJECTIVE To study the effects of a comprehensive discharge planning protocol , design ed specifically for the elderly and implemented by nurse specialists , on patient and caregiver outcomes and cost of care . DESIGN R and omized clinical trial . SETTING Hospital of the University of Pennsylvania . PATIENTS 276 patients and 125 caregivers . Patients were 70 years and older and were placed in selected medical and surgical cardiac diagnostic-related groups . MEASUREMENTS Group differences in patient outcomes ( length of initial hospital stay , length of time between initial hospital discharge and readmission , and rehospitalization rates ) and charges for care ( charges for initial hospitalization , rehospitalizations , health services after discharge , and nurse specialist services ) were measured 2 , 6 , and 12 weeks after discharge . RESULTS From the initial hospital discharge to 6 weeks after discharge , patients in the medical intervention group had fewer readmissions , fewer total days rehospitalized , lower readmission charges , and lower charges for health care services after discharge . No differences in these outcomes were found between the surgical intervention and control groups during this period . CONCLUSIONS Study findings support the need for comprehensive discharge planning design ed for the elderly and implemented by nurse specialists to improve their outcomes after hospital discharge and to achieve cost savings . The findings also suggest that this intervention had its greatest effect in delaying or preventing rehospitalization of patients in the medical intervention group during the first 6 weeks after discharge BACKGROUND One of the causes of postdischarge adverse events is poor discharge communication between hospital-based physicians , patients , and outpatient physicians . The value of hospital discharge software to improve communication and clinical ly relevant outcomes is unknown . OBJECTIVE To measure effects of a discharge software application of computerized physician order entry ( CPOE ) . DESIGN Cluster r and omized controlled trial . SETTING Tertiary care , teaching hospital in central Illinois . PATIENTS A total of 631 in patients discharged to home with high risk for readmission . INTERVENTION Seventy internal medicine hospital physicians were r and omly assigned ( allocation concealed ) to discharge software versus usual care , h and written discharge . MEASUREMENTS Blinded assessment of patient readmission , emergency department visit , and postdischarge adverse event . RESULTS A total of 590 ( 94 % ) patients provided 6-month follow-up data . Generalized estimating equations gave intervention variable coefficients with 95 % confidence interval ( CI ) . When comparing patients assigned to discharge software versus usual care , there was no difference in hospital readmission within 6 months ( 37.0 % versus 37.8 % ; coefficient -0.005 [ 95 % CI , -0.074 to 0.065 ] ; P = 0.894 ) , emergency department visit within 6 months ( 35.4 % versus 40.6 % ; coefficient -0.052 [ 95 % CI , -0.115 to 0.011 ] ; P = 0.108 ) , or adverse event within 1 month ( 7.3 % versus 7.3 % ; coefficient 0.003 [ 95 % CI ; -0.037 to 0.043 ] ; P = 0.884 ) . CONCLUSIONS Discharge software with CPOE did not affect readmissions , emergency department visits , or adverse events after discharge . Future studies should assess other endpoints such as patient perceptions or physician perceptions to see if discharge software has value RATIONALE Care coordination has shown inconsistent results as a mechanism to reduce hospital readmission and postdischarge emergency department ( ED ) visit rates . OBJECTIVE To assess the impact of a supplemental care bundle targeting high-risk elderly in patients implemented by hospital-based staff compared to usual care on a composite outcome of hospital readmission and /or ED visitation at 30 and 60 days following discharge . PATIENTS / METHODS R and omized controlled pilot study in 41 medical in patients predisposed to unplanned readmission or postdischarge ED visitation , conducted at Baylor University Medical Center . The intervention group care bundle consisted of medication counseling/reconciliation by a clinical pharmacist ( CP ) , condition specific education/enhanced discharge planning by a care coordinator ( CC ) , and phone follow-up . RESULTS Groups had similar baseline characteristics . Intervention group readmission/ED visit rates were reduced at 30 days compared to the control group ( 10.0 % versus 38.1 % , P = 0.04 ) , but not at 60 days ( 30.0 % versus 42.9 % , P = 0.52 ) . For those patients who had a readmission/postdischarge ED visit , the time interval to this event was longer in the intervention group compared to usual care ( 36.2 versus 15.7 days , P = 0.05 ) . Study power was insufficient to reliably compare the effects of the intervention on lengths of index hospital stay between groups . CONCLUSIONS A targeted care bundle delivered to high-risk elderly in patients decreased unplanned acute health care utilization up to 30 days following discharge . Dissipation of this effect by 60 days postdischarge defines reasonable expectations for analogous hospital-based educational interventions . Further research is needed regarding the impacts of similar care bundles in larger population s across a variety of inpatient setting ABSTRACT BACKGROUND Patient care transitions are periods of enhanced risk . Discharge summaries have been used to communicate essential information between hospital-based physicians and primary care physicians ( PCPs ) , and may reduce rates of adverse events after discharge . OBJECTIVE To assess PCP satisfaction with an electronic discharge summary ( EDS ) program as compared to conventional dictated discharge summaries . DESIGN Cluster r and omized trial . PARTICIPANTS Four medical teams of an academic general medical service . MEASUREMENTS The primary endpoint was overall discharge summary quality , as assessed by PCPs using a 100-point visual analogue scale . Other endpoints included housestaff satisfaction ( using a 100-point scale ) , adverse outcomes after discharge ( combined endpoint of emergency department visits , readmission , and death ) , and patient underst and ing of discharge details as measured by the Care Transition Model ( CTM-3 ) score ( ranging from 0 to 100 ) . RESULTS 209 patient discharges were included over a 2-month period encompassing 1 housestaff rotation . Surveys were sent out for 188 of these patient discharges , and 119 were returned ( 63 % response rate ) . No difference in PCP-reported overall quality was observed between the 2 methods ( 86.4 for EDS vs. 84.3 for dictation ; P = 0.53 ) . Housestaff found the EDS significantly easier to use than conventional dictation ( 86.5 for EDS vs. 49.2 for dictation ; P = 0.03 ) , but there was no difference in overall housestaff satisfaction . There was no difference between discharge methods for the combined endpoint for adverse outcomes ( 22 for EDS [ 21 % ] vs. 21 for dictation [ 20 % ] ; P = 0.89 ) , or for patient underst and ing of discharge details ( CTM-3 score 80.3 for EDS vs. 81.3 for dictation ; P = 0.81 ) CONCLUSION An EDS program can be used by housestaff to more easily create hospital discharge summaries , and there was no difference in PCP satisfaction OBJECTIVE It has been suggested that continuity of care is hampered because of the lack of communication between emergency departments ( EDs ) and primary care providers . A web-based , st and ardized communication system ( SCS ) that enables family physicians ( FPs ) to visualize information regarding their patients ' ED visits was developed . This paper aims to evaluate the impact of this SCS on continuity of care . METHODS We conducted an open , 4-period crossover , cluster-r and omized controlled trial of 23 FP practice s. During the intervention phase , FPs received detailed reports via SCS , while in the control phase they received mailed copies of the ED notes . Continuity of care was evaluated with a web question naire completed by FPs 21 days after the ED visit . The primary measures of continuity of care were knowledge of ED visit ( quality and quantity ) , patient management and follow-up rate . RESULTS We analyzed a total of 2022 ED visits ( 1048 intervention and 974 control ) . The intervention group received information regarding the ED visit more often ( odds ratio [ OR ] 3.14 , 95 % confidence interval [ CI ] 2.6 - 3.79 ) , found the information more useful ( OR 5.1 , 95 % CI 3.49 - 7.46 ) , possessed a better knowledge of the ED visit ( OR 6.28 , 95 % CI 5.12 - 7.71 ) , felt they could better manage patients ( OR 2.46 , 95 % CI 2.02 - 2.99 ) and initiated actions more often following receipt of information ( OR 1.62 , 95 % CI 1.36 - 1.93 ) . However , there was no significant difference in the follow-up rate at FPs offices ( OR 1.25 , 95 % CI 0.97 - 1.61 ) . CONCLUSION The use of SCS between an ED and FPs led to significant improvements in continuity of care by increasing the usefulness of transferred information and by improving FPs ' perceived patient knowledge and patient management BACKGROUND The diffusion of comprehensive geriatric assessment services has been rather limited in North America partly because of reimbursement and organizational constraints . OBJECTIVE To evaluate the impact of a comprehensive geriatric assessment intervention for frail older patients that is started before hospital discharge and is continued at home . METHODS Patients older than 65 years were selected who had either unstable medical problems , recent functional limitations , or potentially reversible geriatric clinical problems . Patients ( n = 354 ) were r and omly assigned to either the intervention group or a control group . Information on survival , readmissions , nursing home placement , medication use , and health status was collected at 30 and 60 days after hospital discharge . RESULTS No differences were observed between the two treatment groups in survival , hospital readmission , or nursing home placement by 60 days . After adjustment for baseline characteristics , no significant differences were observed between the two groups on measures of physical functioning , social functioning , role limitations , health perceptions , pain , mental health , energy and /or fatigue , health change , or overall well-being . CONCLUSIONS Although efficacy has been demonstrated for some forms of comprehensive geriatric assessment , the types of services that are easier to establish ( inpatient consultation services and ambulatory assessment ) have not been shown to improve outcomes . Our results indicate that outcomes are unaffected by a limited form of comprehensive geriatric assessment begun in the hospital and completed at home . Further efforts are needed to develop and to evaluate realistic approaches to comprehensive geriatric assessment BACKGROUND Adverse events ( AEs ) are adverse outcomes caused by medical care . Several studies have indicated that a substantial number of patients experience AEs before or during hospitalization . However , few data describe AEs after hospital discharge . We determined the incidence , severity , preventability and ameliorability of AEs in patients discharged from the general internal medicine service of a Canadian hospital . METHODS At a multisite Canadian teaching hospital , we prospect ively studied patients who were consecutively discharged home or to a seniors ' residence from the general internal medicine service during a 14-week interval in 2002 . We used telephone interview and chart review to identify outcomes after discharge . Two physicians independently review ed each outcome to determine if the patient experienced an AE . The severity , preventability and ameliorability of all AEs were classified . RESULTS During the study period , outcomes were determined for 328 of the 361 eligible patients , who averaged 71 years of age ( interquartile range 54 - 81 years ) . After discharge , 76 of the 328 patients experienced at least 1 AE ( overall incidence 23 % , 95 % confidence interval [ CI ] 19%-28 % ) . The AE severity ranged from symptoms only ( 68 % of the AEs ) or symptoms associated with a nonpermanent disability ( 25 % ) to permanent disability ( 3 % ) or death ( 3 % ) . The most common AEs were adverse drug events ( 72 % ) , therapeutic errors ( 16 % ) and nosocomial infections ( 11 % ) . Of the 76 patients , 38 had an AE that was either preventable or ameliorable ( overall incidence 12 % , 95 % CI 9%-16 % ) . INTERPRETATION Approximately one-quarter of patients in our study had an AE after hospital discharge , and half of the AEs were preventable or ameliorable Older adults often receive suboptimal care during hospitalizations and transitions to postacute setting s. Inpatient geriatric services have been shown to increase care quality but have not improved patient outcomes consistently . Acute Care for the Elderly units improve patient outcomes but are re source intensive . Transitional care has been shown to reduce hospital readmissions and healthcare costs . This article describes the Geriatric Floating Interdisciplinary Transition Team ( Geri-FITT ) , a model that combines the strengths of inpatient geriatric evaluation and comanagement and transitional care models by creating an inpatient comanagement service that also delivers transitional care . The Geri-FITT model is design ed to improve the hospital care of older adults and their transitions to postacute setting s. In Geri-FITT , a geriatrician-geriatric nurse practitioner team assesses patients , comanages geriatric syndromes , provides staff education , encourages patient self-management , communicates with primary care providers , and follows up with patients soon after discharge . This pilot cohort study of Geri-FITT included hospitalized patients aged 70 and older on four general medicine services ( two Geri-FITT , two usual care ) at an academic medical center ( N=717 ) . The study assessed the effect of Geri-FITT on patients ' care transition quality ( Care Transitions Measure ) and their satisfaction with hospital care ( four questions ) . The results indicate that Geri-FITT is associated with slightly higher , though not statistically significantly so , quality care transitions and greater patient satisfaction with inpatient care . Geri-FITT may be a feasible approach to enhancing inpatient management and transitional care for older adults . Further study of its effect on these and other outcomes in other healthcare setting s seems warranted OBJECTIVES to test the hypothesis as to whether persons newly discharged into the community following an acute stroke and assigned a stroke case manager would experience , compared to usual post-hospital care , better health-related quality of life ( HRQL ) , fewer emergency room visits and less non-elective hospitalisations . DESIGN a stratified , balanced , evaluator-blinded , r and omised clinical trial . SETTING five university-affiliated acute-care hospitals in Montreal , Quebec , Canada . PARTICIPANTS persons ( n = 190 ) returning home directly from the acute-care hospital following a first or recurrent stroke with a need for health care supervision post-discharge because of low function , co-morbidity , or isolation . INTERVENTION for 6 weeks following hospital discharge a nurse stroke care manager maintained contact with patients through home visits and telephone calls design ed to coordinate care with the person 's personal physician and link the stroke survivor into community-based stroke services . MEASUREMENTS the primary outcome was the Physical Component Summary ( PCS ) of the Short-Form (SF)-36 survey . A secondary outcome was utilisation of health services . Also measured was the impact of stroke on functioning . Measurements were made at hospital discharge ( baseline ) , following the 6-week intervention and at 6-months post-stroke . RESULTS the average age of the participants was 70 years . Discharge was achieved on average 12 days post-stroke and most participants had had a stroke of moderate severity . There were no differences between groups on the primary outcome measure , health services utilisation , or any of the secondary outcome measures . CONCLUSION for this population , there was no evidence that this type of passive case management inferred any added benefit in terms of improvement in health-related quality of life or reduction in health services utilisation and stroke impact , than usual post-discharge management OBJECTIVES To explore the 2-year outcomes of an interdisciplinary intervention for elderly patients with hip fracture . DESIGN R and omized experimental design . SETTING A 3,000-bed medical center in northern Taiwan . PARTICIPANTS Patients with hip fracture ( N=162 ) : 80 in the intervention group and 82 in the usual care control group . INTERVENTION An interdisciplinary program of geriatric consultation , continuous rehabilitation , and discharge planning . MEASUREMENTS Outcomes ( clinical outcomes , self-care ability , health-related quality of life ( HRQoL ) , service utilization , and depressive symptoms ) were assessed 1 , 3 , 6 , 12 , 18 , and 24 months after discharge . Self-care ability ( ability to perform activities of daily living ( ADLs ) ) was measured using the Chinese Barthel Index . HRQoL was measured using the Medical Outcomes Study 36-item Short Form Survey , Taiwan version ( SF-36 ) . Depressive symptoms were measured using the Chinese Geriatric Depression Scale , short form . RESULTS Subjects in the intervention group had significantly better ratios of hip flexion ( beta=5.43 , P<.001 ) , better performance on ADLs ( beta=9.22 , P<.001 ) , better recovery of walking ability ( odds ratio (OR)=2.23 , P<.001 ) , fewer falls ( OR=0.56 , P=.03 ) , fewer depressive symptoms ( beta=-1.31 , P=.005 ) , and better SF-36 physical summary scores ( beta=6.08 , P<.001 ) than the control group during the first 24 months after discharge . The intervention did not affect the peak force of the fractured limb 's quadriceps , mortality , service utilization , or SF-36 mental summary score . CONCLUSION The interdisciplinary intervention for hip fracture benefited elderly persons with hip fracture by improving clinical outcomes , self-care ability , and physical health-related outcomes and by decreasing depressive symptoms during the first 24 months after hospital discharge BACKGROUND Poorly executed transfers of older patients from hospitals to long-term care facilities carry the risk of fragmentation of care , poor clinical outcomes , inappropriate use of emergency department services , and hospital readmission . OBJECTIVE This study was conducted to assess the impact of adding a pharmacist transition coordinator on evidence -based medication management and health outcomes in older adults undergoing first-time transfer from a hospital to a long-term care facility . METHODS This r and omized , single-blind , controlled trial enrolled hospitalized older adults awaiting transfer to a long-term residential care facility for the first time . Patients were r and omized either to receive the services of the pharmacist transition coordinator ( intervention group ) or to undergo the usual hospital discharge process ( control group ) . The intervention included medication-management transfer summaries from hospitals , timely coordinated medication review s by accredited community pharmacists , and case conferences with physicians and pharmacists . The primary outcome was the quality of prescribing , measured using the Medication Appropriateness Index ( MAI ) . Secondary outcomes were emergency department visits , hospital readmissions , adverse drug events , falls , worsening mobility , worsening behaviors , increased confusion , and worsening pain . RESULTS One hundred ten older adults ( 67 women , 43 men ; mean [ SD ] age , 82.7 [ 6.4 ] years ) were recruited from 3 metropolitan hospitals and assigned to 85 metropolitan long-term care facilities . Fifty-six patients were r and omized to the intervention group and 54 to the control group ; 44 patients in each group were evaluable at 8-week follow-up . There were no significant differences in baseline characteristics between treatment groups , with the exception of the number of medications discontinued during hospitalization : a mean of 1.1 more drugs was discontinued in the control group compared with the intervention group ( P = 0.011 ) . The majority of patients ( 35 [ 62.5 % ] in the intervention group , 41 [ 76.0 % ] in the control group ) changed physicians as part of the transition to a long-term care facility . At 8-week follow-up , there was no change in MAI from baseline in the intervention group , whereas it had worsened in the control group ( mean [ 95 % CI ] , 2.5 [ 1.4 - 3.7 ] vs 6.5 [ 3.9 - 9.1 ] , respectively ; P = 0.007 ) . Patients who received the intervention and were alive at follow-up exhibited a significant protective effect of the intervention against worsening pain ( relative risk ratio [ 95 % CI ] , 0.55 [ 0.32 - 0.94 ] ; P = 0.023 ) and hospital usage ( i.e. , the combination of emergency department visits and hospital readmissions ) ( 0.38 [ 0.15 - 0.99 ] ; P = 0.035 ) , but did not differ from control patients in terms of adverse drug events ( 1.05 [ 0.66 - 1.68 ] ) , falls ( 1.19 [ 0.71 - 1.99 ] ) , worsening mobility ( 0.39 [ 0.13 - 1.15 ] ) , worsening behaviors ( 0.52 [ 0.25 - 1.10 ] ) , or increased confusion ( 0.59 [ 0.28 - 1.22 ] ) . When data for patients who had died were included , the intervention had no effect on hospital usage in all patients ( 0.58 [ 0.28 - 1.21 ] ) . CONCLUSIONS Older people transferring from hospital to a long-term care facility are vulnerable to fragmentation of care and adverse events . In this study , use of a pharmacist transition coordinator improved aspects of inappropriate use of medicines across health sectors BACKGROUND Hospital discharge summaries communicate information necessary for continuing patient care . They are most commonly generated by voice dictation and are often of poor quality . The objective of this study was to compare discharge summaries created by voice dictation with those generated from a clinical data base . METHODS A r and omized clinical trial was performed in which discharge summaries for patients discharged from a general internal medicine service at a tertiary care teaching hospital in Ottawa were created by voice dictation ( 151 patients ) or from a data base ( 142 patients ) . Patients had been admitted between September 1996 and June 1997 . The trial was preceded by a baseline cohort study in which all summaries were created by dictation . For the data base group , information on forms completed by housestaff was entered into a data base and collated into a discharge summary . For the dictation group , housestaff dictated narrative letters . The proportion of patients for whom a summary was generated within 4 weeks of discharge was recorded . Physicians receiving the summary rated its quality , completeness , organization and timeliness on a 100-mm visual analogue scale . Housestaff preference was also determined . RESULTS Patients in the data base group and the dictation group were similar . A summary was much more likely to be generated within 4 weeks of discharge for patients in the data base group than for those in the dictation group ( 113 [ 79.6 % ] v. 86 [ 57.0 % ] ; p < 0.001 ) . Summary quality was similar ( mean rating 72.7 [ st and ard deviation ( SD ) 19.3 ] v. 74.9 [ SD 16.6 ] ) , as were assessment s of completeness ( 73.4 [ SD 19.8 ] v. 78.2 [ SD 14.9 ] ) , organization ( 77.4 [ SD 16.3 ] v. 79.3 [ SD 17.2 ] ) and timeliness ( 70.3 [ SD 21.9 ] v. 66.2 [ SD 25.6 ] ) . Many information items of interest were more likely to be included in the data base-generated summaries . The data base system created summaries faster and was preferred by housestaff . Dictated summaries in the baseline and r and omized studies were similar , which indicated that the control group was not substantially different from the baseline cohort . INTERPRETATION The data base system significantly increased the likelihood that a discharge summary was created . Housestaff preferred the data base system for summary generation . Physicians thought that the quality of summaries generated by the 2 methods was similar . The use of computer data bases to create hospital discharge summaries is promising and merits further study and refinement 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 OBJECTIVES To study the effects of comprehensive geriatric assessment ( CGA ) and multidisciplinary intervention on elderly patients sent home from the emergency department ( ED ) . DESIGN Prospect i ve , r and omized , controlled trial with 18 months of follow-up . SETTING Large medical school-affiliated public hospital in an urban setting in Sydney , Australia . PARTICIPANTS A total of 739 patients aged 75 and older discharged home from the ED were r and omized into two groups . INTERVENTION Patients r and omized to the treatment group underwent initial CGA and were followed at home for up to 28 days by a hospital-based multidisciplinary outreach team . The team implemented or coordinated recommendations . The control group received usual care . MEASUREMENTS The primary outcome measure was all admissions , to the hospital within 30 days of the initial ED visit . Secondary outcome measures were elective and emergency admissions , and nursing home admissions and mortality . Additional outcomes included physical function ( Barthel Index ( total possible score=20 ) and instrumental activities of daily living ( /12 ) and cognitive function ( mental status question naire ( /10 ) ) . RESULTS Intervention patients had a lower rate of all admissions to the hospital during the first 30 days after the initial ED visit ( 16.5 % vs 22.2 % ; P=.048 ) , a lower rate of emergency admissions during the 18-month follow-up ( 44.4 % vs 54.3 % ; P=.007 ) , and longer time to first emergency admission ( 382 vs 348 days ; P=.011 ) . There was no difference in admission to nursing homes or mortality . Patients r and omized to the intervention group maintained a greater degree of physical and mental function ( Barthel Index change from baseline at 6 months : -0.25 vs -0.75 ; P<.001 ; mental status question naire change from baseline at 12 months : -0.21 vs -0.64 ; P<.001 ) . CONCLUSION CGA and multidisciplinary intervention can improve health outcomes of older people at risk of deteriorating health and admission to hospital . Patients aged 75 and older should be referred for CGA after an ED visit Context Emergency department visits and rehospitalizations are common after hospital discharge . Contribution This trial demonstrated that a nurse discharge advocate and clinical pharmacist working together to coordinate hospital discharge , educate patients , and reconcile medications led to fewer follow-up emergency visits and rehospitalizations than usual care alone . Caution The trial was conducted at a single center , and not all eligible patients were enrolled . Implication A systematic approach to hospital discharges can reduce unnecessary health service use . The Editors One in 5 hospitalizations is complicated by postdischarge adverse events ( 1 , 2 ) , some of which may lead to preventable emergency department visits or readmissions . Despite this finding , hospital discharge procedures have not been st and ardized ( 3 ) . In addition , the declining presence of primary care providers ( PCPs ) in hospitals has not been adequately accompanied by systems to ensure that patient data are transferred to subsequent caregivers ( 4 , 5 ) . For example , discharge summaries frequently lack critical data and are not sent to the PCP in a timely fashion ( 6 , 7 ) , result ing in outpatient clinicians being unaware of test results that were pending at discharge ( 8) and evaluations that were scheduled to be done after discharge not being completed ( 9 ) . Similarly , patients are often left unprepared at discharge ; many do not underst and their discharge medications and can not recall their chief diagnoses ( 10 ) . With more than 32 million adult discharges in the United States each year ( 11 ) , these deficiencies in the transition of care increase illness , unnecessary hospital utilization , and cost . Some peridischarge interventions have shown a reduction in hospital readmission rates and cost ( 1214 ) , emergency department visits ( 15 ) , and postdischarge adverse events ( 16 ) , whereas some have shown little or no effect ( 1720 ) . Peridischarge interventions have also shown improved PCP follow-up and outpatient work-ups ( 21 ) and higher patient satisfaction ( 15 ) . Most of these studies have focused on specific diagnoses ( 14 , 22 , 23 ) or highly selected population s , such as geriatric adults ( 12 , 13 , 19 , 24 ) . Some have focused on specific aspects of the discharge , such as increasing access to primary care follow-up ( 25 ) , connecting with transitional nursing services ( 26 ) , or improving patients ' ability to advocate for themselves after discharge ( 12 ) . To date , no study has evaluated a st and ardized discharge intervention that includes patient education , comprehensive discharge planning , and postdischarge telephone reinforcement in a general medical population . In 2004 , we began an in-depth examination of hospital discharge , for which we design ed a package of services to minimize discharge failuresa process called reengineered discharge ( RED ) ( Table 1 ) ( 3 , 27 ) . We did a r and omized , controlled trial to evaluate the clinical effect of implementing RED among patients admitted to a general medical service . Table 1 . Components of Reengineered Hospital Discharge Methods Setting and Participants We conducted a 2-group , r and omized , controlled trial of English-speaking patients 18 years of age or older who were admitted to the medical teaching service of Boston Medical Center , Boston , Massachusettsa large , urban , safety-net hospital with an ethnically diverse patient population . Patients had to have a telephone , be able to comprehend study details and the consent process in English , and have plans to be discharged to a U.S. community . We did not enroll patients if they were admitted from a skilled nursing facility or other hospital , transferred to a different hospital service before enrollment , admitted for a planned hospitalization , were on hospital pre caution s or suicide watch , or were deaf or blind . Boston University 's institutional review board approved all study activities . R and omization Each morning , a list of admitted patients was review ed for initial eligibility ( hospital location , age , date and time of admission , and previous enrollment ) . Last names of potential participants were ranked by using a r and om-number sequence to determine the order in which to approach patients for enrollment . A trained research assistant then approached each patient and further determined eligibility according to inclusion and exclusion criteria ( Figure 1 ) . Figure 1 . Study flow diagram . * Patients did not meet inclusion criteria if they were admitted from or planned discharge to an institutional setting ( n= 74 ) , planned hospitalization ( n= 3 ) or discharge to a non-U.S. community ( n= 5 ) , were transferred to different hospital service ( n= 8) , did not speak English ( n= 371 ) or have a telephone ( n= 71 ) , were on hospital pre caution s ( n= 274 ) or suicide watch with a sitter ( n= 10 ) , were unable to consent ( n= 181 ) , had sickle cell disease as the admitting diagnosis ( n= 38 ) , had privacy status ( n= 8) , were deaf or blind ( n= 2 ) , or other ( n= 4 ) . Usual care participants did not meet eligibility criteria if they were discharged to a nursing facility ( n= 28 ) , were transferred to another hospital service ( n= 1 ) , were previously enrolled ( n= 1 ) , died during index admission ( n= 2 ) , requested to be removed ( n= 5 ) , or other ( n= 3 ) . Intervention participants did not meet eligibility criteria if they were discharged to a nursing facility ( n= 21 ) , were transferred to another hospital service ( n= 6 ) , died during index admission ( n= 1 ) , requested to be removed ( n= 2 ) , or other ( n= 8) . 107 intervention participants did not receive a reinforcement call because they could not be reached by telephone ( n= 93 ) , they were readmitted the same or next day ( n= 2 ) , there was no staffing coverage ( n= 8) , or other ( n= 4 ) . By using block r and omization ( 28 ) with varying block sizes of 6 and 8 , we r and omly arranged index cards indicating either the usual care or intervention group . We placed the cards in opaque envelopes labeled consecutively with study numbers . We assigned eligible participants who consented to enrollment to a study group by revealing the concealed index card . This process continued until 2 participants were enrolled each day of the week ( or 3 participants if the first 2 participants were r and omly assigned to the usual care group ) . This protocol ensured that research assistants could not selectively choose potential participants for enrollment or predict assignment . Participants r and omly assigned to usual care received no further intervention . There were 40 participants in the usual care group and 38 in the intervention group who were enrolled but no longer met inclusion criteria at discharge ( most commonly because they were discharged to a nursing facility ) . Because the primary analysis was by intention to treat , we included these participants in the analysis , with the exception of those who died before index discharge , requested to be removed , or were previously enrolled ( Figure 1 ) . Interventions Nurse discharge advocates ( DAs ) carried out all aspects of the in-hospital intervention . We hired 6 part-time DAs to work with intervention participants to ensure coverage by 1 DA 7 days a week , 5 hours a day . We trained all DAs to deliver the RED intervention by using a manual containing detailed scripts , observation of relevant clinical interactions , and simulated practice sessions . The primary goals of the DA were to coordinate the discharge plan with the hospital team and educate and prepare the participant for discharge . At admission , the DA completed the RED intervention components outlined in Table 1 . Additional information about the DA training manual is published elsewhere ( 3 ) and can be found on our Web site ( www.bu.edu/fammed/projectred/index.html ) . With information collected from the hospital team and the participant , the DA created the after-hospital care plan ( AHCP ) , which contained medical provider contact information , date s for appointments and tests , an appointment calendar , a color-coded medication schedule , a list of tests with pending results at discharge , an illustrated description of the discharge diagnosis , and information about what to do if a problem arises . Information for the AHCP was manually entered into a Microsoft Word ( Microsoft , Redmond , Washington ) template , printed , and spiral-bound to produce an individualized , color booklet design ed to be accessible to individuals with limited health literacy . By using scripts from the training manual , the DA used a teach-back methodology ( 29 ) to review the contents of the AHCP with the participant . On the day of discharge , the AHCP and discharge summary were faxed to the PCP . A clinical pharmacist telephoned the participants 2 to 4 days after the index discharge to reinforce the discharge plan by using a scripted interview . The pharmacist had access to the AHCP and hospital discharge summary and , over several days , made at least 3 attempts to reach each participant . The pharmacist asked participants to bring their medications to the telephone to review them and address medication-related problems ; the pharmacist communicated these issues to the PCP or DA . Outcomes Measures and Follow-up At the time of recruitment , research assistants collected baseline data , including sociodemographic characteristics ; the Short Form-12 Health Survey , Version 2 ( 30 ) ; the depression subscale from the Patient Health Question naire-9 ( 31 ) ; and the Rapid Estimate of Adult Literacy in Medicine ( 32 ) . We calculated the Charlson Comorbidity Index score by using primary and secondary diagnoses recorded on the index admission discharge summary ( 33 ) . We determined the number of hospital admissions and emergency department visits in the 6 months before index admission through medical record review ( Boston Medical Center hospital utilization ) and participant report ( all other hospital utilization ) . The primary end point was the rate of hospital utilizationthe total number of emergency department visits and readmissions per participant within 30 days of the index discharge . OBJECTIVES To evaluate the effectiveness of an intensive community nurse (CN)-supported discharge program in preventing hospital readmissions of older patients with chronic lung disease ( CLD ) . DESIGN R and omized , controlled trial . SETTING Two acute hospitals in the same health region in Hong Kong . PARTICIPANTS One hundred fifty-seven hospitalized patients aged 60 and older with a primary diagnosis of CLD and at least one hospital admission in the previous 6 months . INTERVENTION CNs made home visits within 7 days of discharge , then weekly for 4 weeks and monthly until 6 months . CNs coordinated closely with a geriatric or respiratory specialist in hospital . Subjects had telephone access to CNs during normal working hours from Monday to Saturday . MEASUREMENTS The primary outcome was the rate of unplanned readmission within 6 months . The secondary outcomes were the rate of unplanned readmission within 28 days , number of unplanned readmissions , hospital bed days , accident and emergency room attendance , functional and psychosocial status , and caregiver burden . RESULTS One hundred forty hospitalized patients completed the trial . Intervention group subjects had a higher rate of unplanned readmission within 6 months than control group subjects ( 76 % vs 62 % , P=.080 , chi2 test ) . There was no significant group difference in any of the secondary outcomes except that intervention group subjects did better on social h and icap scores . CONCLUSION There was no evidence that an intensive CN-supported discharge program can prevent hospital readmissions in older patients with CLD OBJECTIVE To evaluate the benefits of coordinating community services through the Post-Acute Care ( PAC ) program in older patients after discharge from hospital . DESIGN Prospect i ve multicentre , r and omised controlled trial with six months of follow-up with blinded outcome measurement . SETTING Four university-affiliated metropolitan general hospitals in Victoria . PARTICIPANTS All patients aged 65 years and over who were discharged between August 1998 and October 1999 and required community services after discharge . INTERVENTIONS Participants were r and omly allocated to receive services of a Post-Acute Care ( PAC ) coordinator ( intervention ) versus usual discharge planning ( control ) . MAIN OUTCOME MEASURES Comparison of quality of life and carer stress at one-month post-discharge , mortality , hospital readmissions , use of community services and community and hospital costs over the six months post-discharge . RESULTS 654 patients were r and omised , and 598 were included in the analysis ( 311 in the PAC group and 287 in the control group ) . There was no difference in mortality between the groups ( both 6 % ) , but significantly greater overall quality -of-life scores at one-month follow-up in the PAC group . There was no difference in unplanned readmissions , but PAC patients used significantly fewer hospital bed-days in the six months after discharge ( mean , 3.0 days ; 95 % CI , 2.1 - 3.9 ) than control patients ( 5.2 days ; 95 % CI , 3.8 - 6.7 ) . Total costs ( including hospitalisation , community services and the intervention ) were lower in the PAC than the control group ( mean difference , $ 1545 ; 95 % CI , $ 11-$3078 ) . CONCLUSIONS The PAC program is beneficial in the transition from hospital to the community in older patients AIMS AND OBJECTIVES This study aim ed to evaluate the effectiveness of a comprehensive discharge-planning service for hip fracture patients , including length of stay , functional status , self-care knowledge and quality of life ( QOL ) . BACKGROUND Hip fractures are the most devastating result of osteoporosis . Care of these patients from the moment they enter the hospital until discharge and postdischarge is a challenging task , requiring a coordinated approach by an interdisciplinary team . DESIGN An experimental design was used . Methods . Fifty hip fracture patients were recruited from a medical centre in Taipei , Taiwan and r and omly divided into two groups . The control group received routine discharge nursing care and the experimental group received comprehensive discharge planning . After patient admission , research ers assessed discharge-planning needs , provided discharge nursing instruction , coordinated services and determined discharge placement based on assessment results . RESULTS ( i ) Mean age of 50 hip fracture patients was 78.75 ( SD 6.99 ) years . Mean length of stay was 6.04 ( SD 2.41 ) days for the experimental group and 6.29 ( SD 2.17 ) for the control group . Difference between groups was not significant ( t = -0.394 , p = 0.696 ) . ( ii ) The self-care knowledge of the experimental group was higher than that of the control group ( F = 11.569 , p = 0.001 ) . ( iii ) Significant improvements were observed in functional status of both groups at three months postdischarge , with no significant differences observed between groups . However , the functional status of experimental group patients showed a slightly better trend than that of the control group . ( iv ) At three months postdischarge , QOL of experimental group patients was better than control group patients . CONCLUSIONS A comprehensive discharge-planning service can improve hip fracture patients ' self-care knowledge and QOL . RELEVANCE TO CLINICAL PRACTICE Results of this study can be used clinical ly as a basis for practical implementation of discharge-planning services in fracture patients |
1,251 | 25,401,930 | On the cross-sectional level , higher water consumption seems to be associated with higher weight status .
In contrast , longitudinal studies suggest a weight-reducing effect of water consumption , but evidence for a causal association is still low | OBJECTIVE Water is recommended to replace sugar-containing beverages for prevention of childhood obesity .
Because this recommendation is not evidence -based yet , the existing evidence on the association between water consumption and body weight outcomes was summarized . | OBJECTIVE . The study tested whether a combined environmental and educational intervention solely promoting water consumption was effective in preventing overweight among children in elementary school . METHODS . The participants in this r and omized , controlled cluster trial were second- and third- grade rs from 32 elementary schools in socially deprived areas of 2 German cities . Water fountains were installed and teachers presented 4 prepared classroom lessons in the intervention group schools ( N = 17 ) to promote water consumption . Control group schools ( N = 15 ) did not receive any intervention . The prevalence of overweight ( defined according to the International Obesity Task Force criteria ) , BMI SD scores , and beverage consumption ( in glasses per day ; 1 glass was defined as 200 mL ) self-reported in 24-hour recall question naires , were determined before ( baseline ) and after the intervention . In addition , the water flow of the fountains was measured during the intervention period of 1 school year ( August 2006 to June 2007 ) . RESULTS . Data on 2950 children ( intervention group : N = 1641 ; control group : N = 1309 ; age , mean ± SD : 8.3 ± 0.7 years ) were analyzed . After the intervention , the risk of overweight was reduced by 31 % in the intervention group , compared with the control group , with adjustment for baseline prevalence of overweight and clustering according to school . Changes in BMI SD scores did not differ between the intervention group and the control group . Water consumption after the intervention was 1.1 glasses per day greater in the intervention group . No intervention effect on juice and soft drink consumption was found . Daily water flow of the fountains indicated lasting use during the entire intervention period , but to varying extent . CONCLUSION . Our environmental and educational , school-based intervention proved to be effective in the prevention of overweight among children in elementary school , even in a population from socially deprived areas BACKGROUND The consumption of beverages that contain sugar is associated with overweight , possibly because liquid sugars do not lead to a sense of satiety , so the consumption of other foods is not reduced . However , data are lacking to show that the replacement of sugar-containing beverages with noncaloric beverages diminishes weight gain . METHODS We conducted an 18-month trial involving 641 primarily normal-weight children from 4 years 10 months to 11 years 11 months of age . Participants were r and omly assigned to receive 250 ml ( 8 oz ) per day of a sugar-free , artificially sweetened beverage ( sugar-free group ) or a similar sugar-containing beverage that provided 104 kcal ( sugar group ) . Beverages were distributed through schools . At 18 months , 26 % of the children had stopped consuming the beverages ; the data from children who did not complete the study were imputed . RESULTS The z score for the body-mass index ( BMI , the weight in kilograms divided by the square of the height in meters ) increased on average by 0.02 SD units in the sugar-free group and by 0.15 SD units in the sugar group ; the 95 % confidence interval ( CI ) of the difference was -0.21 to -0.05 . Weight increased by 6.35 kg in the sugar-free group as compared with 7.37 kg in the sugar group ( 95 % CI for the difference , -1.54 to -0.48 ) . The skinfold-thickness measurements , waist-to-height ratio , and fat mass also increased significantly less in the sugar-free group . Adverse events were minor . When we combined measurements at 18 months in 136 children who had discontinued the study with those in 477 children who completed the study , the BMI z score increased by 0.06 SD units in the sugar-free group and by 0.12 SD units in the sugar group ( P=0.06 ) . CONCLUSIONS Masked replacement of sugar-containing beverages with noncaloric beverages reduced weight gain and fat accumulation in normal-weight children . ( Funded by the Netherl and s Organization for Health Research and Development and others ; DRINK Clinical Trials.gov number , NCT00893529 . ) OBJECTIVE : To examine the long-term relationship between changes in water and beverage intake and weight change . SUBJECTS : Prospect i ve cohort studies of 50 013 women aged 40–64 years in the Nurses ’ Health Study ( NHS , 1986–2006 ) , 52 987 women aged 27–44 years in the NHS II ( 1991–2007 ) and 21 988 men aged 40–64 years in the Health Professionals Follow-up Study ( 1986–2006 ) without obesity and chronic diseases at baseline . MEASURES : We assessed the association of weight change within each 4-year interval , with changes in beverage intakes and other lifestyle behaviors during the same period . Multivariate linear regression with robust variance and accounting for within-person repeated measures were used to evaluate the association . Results across the three cohorts were pooled by an inverse-variance-weighted meta- analysis . RESULTS : Participants gained an average of 1.45 kg ( 5th to 95th percentile : −1.87 to 5.46 ) within each 4-year period . After controlling for age , baseline body mass index and changes in other lifestyle behaviors ( diet , smoking habits , exercise , alcohol , sleep duration , TV watching ) , each 1 cup per day increment of water intake was inversely associated with weight gain within each 4-year period ( −0.13 kg ; 95 % confidence interval ( CI ) : −0.17 to −0.08 ) . The associations for other beverages were : sugar-sweetened beverages ( SSBs ) ( 0.36 kg ; 95 % CI : 0.24–0.48 ) , fruit juice ( 0.22 kg ; 95 % CI : 0.15–0.28 ) , coffee ( −0.14 kg ; 95 % CI : −0.19 to −0.09 ) , tea ( −0.03 kg ; 95 % CI : −0.05 to −0.01 ) , diet beverages ( −0.10 kg ; 95 % CI : −0.14 to −0.06 ) , low-fat milk ( 0.02 kg ; 95 % CI : −0.04 to 0.09 ) and whole milk ( 0.02 kg ; 95 % CI : −0.06 to 0.10 ) . We estimated that replacement of 1 serving per day of SSBs by 1 cup per day of water was associated with 0.49 kg ( 95 % CI : 0.32–0.65 ) less weight gain over each 4-year period , and the replacement estimate of fruit juices by water was 0.35 kg ( 95 % CI : 0.23–0.46 ) . Substitution of SSBs or fruit juices by other beverages ( coffee , tea , diet beverages , low-fat and whole milk ) were all significantly and inversely associated with weight gain . CONCLUSION : Our results suggest that increasing water intake in place of SSBs or fruit juices is associated with lower long-term weight gain OBJECTIVE To determine the efficacy of a 2-year obesity prevention program in African American girls . DESIGN Memphis GEMS ( Girls ' health Enrichment Multi-site Studies ) was a controlled trial in which girls were r and omly assigned to an obesity prevention program or alternative intervention . SETTING Local community centers and YWCAs ( Young Women 's Christian Associations ) in Memphis , Tennessee . PARTICIPANTS Girls aged 8 to 10 years ( N = 303 ) who were identified by a parent or guardian as African American and who had a body mass index ( BMI ) at or higher than the 25th percentile for age or 1 parent with a BMI of 25 or higher . INTERVENTIONS Group behavioral counseling to promote healthy eating and increased physical activity ( obesity prevention program ) or self-esteem and social efficacy ( alternative intervention ) . MAIN OUTCOME MEASURE The BMI at 2 years . RESULTS The BMI increased in all girls with no treatment effect ( obesity prevention minus alternative intervention ) at 2 years ( mean , 0.09 ; 95 % confidence interval [ CI ] , -0.40 to 0.58 ) . Two-year treatment effects in the expected direction were observed for servings per day of sweetened beverages ( mean , -0.19 ; 95 % CI , -0.39 to 0.09 ) , water ( mean , 0.21 ; 95 % CI , 0.03 to 0.40 ) , and vegetables ( mean , 0.15 ; 95 % CI,-0.02 to 0.30 ) , but there were no effects on physical activity . Post hoc analyses suggested a treatment effect in younger girls ( P for interaction = .08 ) . The mean BMI difference at 2 years was -2.41 ( 95 % CI , -4.83 to 0.02 ) in girls initially aged 8 years and -1.02 ( 95 % CI , -2.31 to 0.27 ) in those initially aged 10 years . CONCLUSIONS The lack of significant BMI change at 2 years indicates that this intervention alone is insufficient for obesity prevention . Effectiveness may require more explicit behavior change goals and a stronger physical activity component as well as supportive changes in environmental context CONTEXT Recently , we showed that drinking 500 ml water induces thermogenesis in normal-weight men and women . OBJECTIVE We now repeated these studies in a r and omized , controlled , crossover trial in overweight or obese otherwise healthy subjects ( eight men and eight women ) , comparing also the effects of 500 ml isoosmotic saline or 50 ml water . RESULTS Only 500 ml water increased energy expenditure by 24 % over the course of 60 min after ingestion , whereas isoosmotic saline and 50 ml water had no effect . Heart rate and blood pressure did not change in these young , healthy subjects . CONCLUSIONS Our data exclude volume-related effects or gastric distension as the mediator of the thermogenic response to water drinking . Instead , we hypothesize the existence of a portal osmoreceptor , most likely an ion channel OBJECTIVE To determine whether an educational programme aim ed at discouraging students from drinking sugar-sweetened beverages could prevent excessive weight gain . DESIGN Forty-seven classes in twenty-two schools were r and omised as intervention or control . SUBJECTS Participants were 1140 , 9 - 12-year-old fourth grade rs ( 435 in the intervention group and 608 in the control group ) . Sugar-sweetened beverages and juice intake were measured through one 24 h recall at baseline and another at the end of the trial . The main outcome was the change in BMI ( BMI = weight (kg)/height ( m2 ) ) , measured at the beginning and at the end of the school year . Intention-to-treat analysis was performed taking into account the cluster ( classes ) effect . RESULTS A statistically significant decrease in the daily consumption of carbonated drinks in the intervention compared to control ( mean difference = -56 ml ; 95 % CI -119 , -7 ml ) was followed by a non-significant overall reduction in BMI , P = 0.33 . However , among those students overweight at baseline , the intervention group showed greater BMI reduction ( -0.4 kg/m2 compared with -0.2 kg/m2 in the control group ( P = 0.11 ) ) , and this difference was statistically significant among girls ( P = 0.009 ) . Fruit juice consumption was slightly increased in the intervention group ( P = 0.08 ) , but not among girls . CONCLUSION Decreasing sugar-sweetened beverages intake significantly reduced BMI among overweight children , and mainly among girls . Efforts to reduce energy intake through liquids need to emphasise overall sweetened beverages and addition of sugar on juices OBJECTIVE We examined whether drinking water per se is associated with drinking less of other beverages and whether changes in BMI are associated with the intake of water and other beverages . DESIGN Secondary analysis of a r and omized trial of fourth grade rs followed over 1 year . SETTING Public schools in the metropolitan area of Rio de Janeiro , Brazil . SUBJECTS Participants were 1134 students aged 10 - 11 years . RESULTS At baseline , a higher frequency of water consumption was associated with a greater daily intake of fruit juice ( P = 0.02 ) and a higher daily frequency of milk ( P = 0.005 ) . In the intervention group , the baseline frequency of water consumption was negatively associated with weight change over 1 year but without statistical significance ( coefficient = -0.08 kg/m2 ; 95 % CI -0.37 , 0.24 kg/m2 ) , whereas fruit juice intake frequency was positively associated with weight change : each increase in fruit juice intake of 1 glass/d was associated with a BMI increase of 0.16 ( 95 % CI 0.02 , 0.30 ) kg/m2 . CONCLUSIONS Our findings do not support a protective effect of water consumption on BMI , but confirm consumption of juice drinks as a risk factor for BMI gain . Students who reported high water consumption also reported high intake of other beverages ; therefore , the promotion of water consumption per se would not prevent excessive weight gain Obesity among Saudi youth is a growing public health challenge . This cross-sectional study measured body mass index ( BMI ) and determined the eating habits and lifestyle of 107 r and omly selected female adolescent students ( age 12 - 15 years ) at schools in Riyadh . The students ' heights and weights were measured and a pre-tested question naire was used to collect data on diet and lifestyle . The majority of the students ' families had monthly income > 10 000 riyals ( US$ 1 = 3.75 riyals ) . About half the students ( 53.3 % ) were within normal weight , 28.6 % were underweight , 12.4 % overweight and 5.7 % obese . The majority of the students did not have healthy dietary or exercise habits . There were no significant differences between BMI category and dietary pattern and lifestyle . Increasing educational programmes with healthy dietary concepts to improve the dietary pattern of female adolescents is recommended BACKGROUND Consumption of sugar-sweetened beverages may cause excessive weight gain . We aim ed to assess the effect on weight gain of an intervention that included the provision of noncaloric beverages at home for overweight and obese adolescents . METHODS We r and omly assigned 224 overweight and obese adolescents who regularly consumed sugar-sweetened beverages to experimental and control groups . The experimental group received a 1-year intervention design ed to decrease consumption of sugar-sweetened beverages , with follow-up for an additional year without intervention . We hypothesized that the experimental group would gain weight at a slower rate than the control group . RESULTS Retention rates were 97 % at 1 year and 93 % at 2 years . Reported consumption of sugar-sweetened beverages was similar at baseline in the experimental and control groups ( 1.7 servings per day ) , declined to nearly 0 in the experimental group at 1 year , and remained lower in the experimental group than in the control group at 2 years . The primary outcome , the change in mean body-mass index ( BMI , the weight in kilograms divided by the square of the height in meters ) at 2 years , did not differ significantly between the two groups ( change in experimental group minus change in control group , -0.3 ; P=0.46 ) . At 1 year , however , there were significant between-group differences for changes in BMI ( -0.57 , P=0.045 ) and weight ( -1.9 kg , P=0.04 ) . We found evidence of effect modification according to ethnic group at 1 year ( P=0.04 ) and 2 years ( P=0.01 ) . In a prespecified analysis according to ethnic group , among Hispanic participants ( 27 in the experimental group and 19 in the control group ) , there was a significant between-group difference in the change in BMI at 1 year ( -1.79 , P=0.007 ) and 2 years ( -2.35 , P=0.01 ) , but not among non-Hispanic participants ( P>0.35 at years 1 and 2 ) . The change in body fat as a percentage of total weight did not differ significantly between groups at 2 years ( -0.5 % , P=0.40 ) . There were no adverse events related to study participation . CONCLUSIONS Among overweight and obese adolescents , the increase in BMI was smaller in the experimental group than in the control group after a 1-year intervention design ed to reduce consumption of sugar-sweetened beverages , but not at the 2-year follow-up ( the prespecified primary outcome ) . ( Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others ; Clinical Trials.gov number , NCT00381160 . ) OBJECTIVE . The role of sugar-sweetened beverages ( SSBs ) in promoting obesity is controversial . Observational data link SSB consumption with excessive weight gain ; however , r and omized , controlled trials are lacking and necessary to resolve the debate . We conducted a pilot study to examine the effect of decreasing SSB consumption on body weight . METHODS . We r and omly assigned 103 adolescents aged 13 to 18 years who regularly consumed SSBs to intervention and control groups . The intervention , 25 weeks in duration , relied largely on home deliveries of noncaloric beverages to displace SSBs and thereby decrease consumption . Change in SSB consumption was the main process measure , and change in body mass index ( BMI ) was the primary end point . RESULTS . All of the r and omly assigned subjects completed the study . Consumption of SSBs decreased by 82 % in the intervention group and did not change in the control group . Change in BMI , adjusted for gender and age , was 0.07 ± 0.14 kg/m2 ( mean ± SE ) for the intervention group and 0.21 ± 0.15 kg/m2 for the control group . The net difference , −0.14 ± 0.21 kg/m2 , was not significant overall . However , baseline BMI was a significant effect modifier . Among the subjects in the upper baseline- BMI tertile , BMI change differed significantly between the intervention ( −0.63 ± 0.23 kg/m2 ) and control ( + 0.12 ± 0.26 kg/m2 ) groups , a net effect of −0.75 ± 0.34 kg/m2 . The interaction between weight change and baseline BMI was not attributable to baseline consumption of SSBs . CONCLUSIONS . A simple environmental intervention almost completely eliminated SSB consumption in a diverse group of adolescents . The beneficial effect on body weight of reducing SSB consumption increased with increasing baseline body weight , offering additional support for American Academy of Pediatrics guidelines to limit SSB consumption OBJECTIVE This paper identifies the anthropometric , parental , and psychosocial characteristics and meal practice s ( e.g. , breakfast skipping and number of meals and snacks consumed ) associated with consumption of total energy , percent energy from fat , fruit , 100 % fruit juice , vegetables , sweetened beverages , and water among 8- to 10-year-old African-American girls . RESEARCH METHODS AND PROCEDURES This study included 114 8- to 10-year-old African-American girls and a parent or primary caregiver . Girls and a parent or primary caregiver completed several dietary question naires . Two 24-hour dietary recalls were conducted with each girl . Height and weight were measured . Separate hierarchical regression analyses were conducted for each dependent dietary variable ; potential field center differences were examined . RESULTS The number of meals and snacks consumed was correlated with energy intake . Lower BMI was related to higher vegetable consumption , and the number of snacks consumed was positively related to sweetened beverage consumption . Greater low-fat food preparation practice s reported by parents were related to lower consumption of fat as a percentage of total energy . DISCUSSION Dietary behavior differed across geographic areas . Low-fat food preparation practice s in the home seemed to be an important influence on the percentage of energy consumed from fat . Greater vegetable consumption was associated with lower BMI . Interventions to prevent excessive weight gain in African-American girls should encourage low-fat food preparation in the home and greater consumption of vegetables CONTEXT A recent study reported that drinking 500 ml of water causes a 30 % increase in metabolic rate . If verified , this previously unrecognized thermogenic property of water would have important implication s for weight-loss programs . However , the concept of a thermogenic effect of water is controversial because other studies have found that water drinking does not increase energy expenditure . OBJECTIVE The objective of the study was to test whether water drinking has a thermogenic effect in humans and , furthermore , determine whether the response is influenced by osmolality or by water temperature . DESIGN This was a r and omized , crossover design . SETTING The study was conducted at a university physiology laboratory . PARTICIPANTS Participants included healthy young volunteer subjects . INTERVENTION Intervention included drinking 7.5 ml/kg body weight ( approximately 518 ml ) of distilled water or 0.9 % saline or 7 % sucrose solution ( positive control ) on different days . In a subgroup of subjects , responses to cold water ( 3 C ) were tested . MAIN OUTCOME MEASURE Resting energy expenditure , assessed by indirect calorimetry for 30 min before and 90 min after the drinks , was measured . RESULTS Energy expenditure did not increase after drinking either distilled water ( P = 0.34 ) or 0.9 % saline ( P = 0.33 ) . Drinking the 7 % sucrose solution significantly increased energy expenditure ( P < 0.0001 ) . Drinking water that had been cooled to 3 C caused a small increase in energy expenditure of 4.5 % over 60 min ( P < 0.01 ) . CONCLUSIONS Drinking distilled water at room temperature did not increase energy expenditure . Cooling the water before drinking only stimulated a small thermogenic response , well below the theoretical energy cost of warming the water to body temperature . These results cast doubt on water as a thermogenic agent for the management of obesity OBJECTIVE To compare the efficacy of non-nutritive sweetened beverages ( NNS ) or water for weight loss during a 12-week behavioral weight loss treatment program . METHODS An equivalence trial design with water or NNS beverages as the main factor in a prospect i ve r and omized trial among 303 men and women was employed . All participants participated in a behavioral weight loss treatment program . The results of the weight loss phase ( 12 weeks ) of an ongoing trial ( 1 year ) that is also evaluating the effects of these two treatments on weight loss maintenance were reported . RESULTS The two treatments were not equivalent with the NNS beverage treatment group losing significantly more weight compared to the water group ( 5.95 kg versus 4.09 kg ; P < 0.0001 ) after 12 weeks . Participants in the NNS beverage group reported significantly greater reductions in subjective feelings of hunger than those in the water group during 12 weeks . CONCLUSION These results show that water is not superior to NNS beverages for weight loss during a comprehensive behavioral weight loss program |
1,252 | 17,415,549 | In the four studies that measured the incidence of diabetes as an outcome , the risk of diabetes was reduced by approximately 50 % ( range 42–63 % ) ; as these studies reported only small changes in physical activity levels , the reduced risk of diabetes is likely to be attributable to factors other than physical activity .
These results indicate that the contribution of physical activity independent of dietary or weight loss changes to the prevention of type 2 diabetes in people with prediabetes is equivocal | Although physical activity is widely reported to reduce the risk of type 2 diabetes in individuals with prediabetes , few studies have examined this issue independently of other lifestyle modifications .
The aim of this review is to conduct a systematic review of controlled trials to determine the independent effect of exercise on glucose levels and risk of type 2 diabetes in people with prediabetes ( IGT and /or IFG ) . | OBJECTIVE Changing dietary and physical activity habits has the potential to postpone or prevent the development of type 2 diabetes . However , it needs to be assessed whether moderate interventions , in agreement with current guidelines for the general population , are effective . We evaluated the impact of a 2-year combined diet and physical activity intervention program on glucose tolerance in Dutch subjects at increased risk for developing diabetes . RESEARCH METHODS AND PROCEDURES Subjects with glucose intolerance were r and omly assigned to either the lifestyle intervention group ( INT ) or control group ( CON ) . The INT received regular dietary advice and was stimulated to increase their physical activity . The CON received a brief leaflet about healthy diet and increased physical activity . Primary outcome measure was the change in glucose tolerance . RESULTS In total , 88 subjects completed 2 years of intervention ( 40 subjects in the INT , 48 subjects in the CON , mean BMI 29.4 kg/m2 ) . Subjects in the INT reduced their body weight , waist circumference , and ( saturated ) fat intake and improved their aerobic capacity . Two-hour plasma glucose concentration declined from 8.7 to 8.0 mM in the INT and rose from 8.6 to 9.4 mM in the CON ( p < 0.01 ) . Subjects adherent to both the diet and exercise intervention showed the largest reduction in 2-hour glucose levels . DISCUSSION Our results showed that a lifestyle intervention program according to general recommendations improves glucose tolerance , even in a less obese and more physical active population . Furthermore , our results underscore the importance of combining diet and physical activity to improve glucose tolerance and insulin resistance Lifestyle modification reduces the risk of developing type 2 diabetes and may have its effect through improving insulin sensitivity , beta-cell function , or both . To determine whether diet and exercise improve insulin sensitivity and /or beta-cell function and to evaluate these effects over time , we quantified insulin sensitivity and the acute insulin response to glucose ( AIRg ) in 62 Japanese Americans ( age 56.5 + /- 1.3 years ; mean + /- SE ) with impaired glucose tolerance ( IGT ) who were r and omized to the American Heart Association ( AHA ) Step 2 diet plus endurance exercise ( n = 30 ) versus the AHA Step 1 diet plus stretching ( n = 32 ) for 24 months . beta-Cell function ( disposition index [ DI ] ) was calculated as S(i ) x AIRg , where S(i ) is the insulin sensitivity index . The incremental area under the curve for glucose ( incAUCg ) was calculated from a 75-g oral glucose tolerance test . Intra-abdominal fat ( IAF ) and subcutaneous fat ( SCF ) areas were measured by computed tomography . At 24 months , the Step 2/endurance group had lower weight ( 63.1 + /- 2.4 vs. 71.3 + /- 2.9 kg ; P = 0.004 ) and IAF ( 75.0 + /- 7.9 vs. 112.7 + /- 10.4 cm(2 ) ; P = 0.03 ) and SCF ( 196.5 + /- 18.0 vs. 227.7 + /- 19.9 cm(2 ) ; P < 0.001 ) areas , greater S(i ) ( 4.7 + /- 0.5 vs. 3.3 + /- 0.3 x 10(-5 ) min . pmol(-1 ) . l(-1 ) ; P = 0.01 ) , and a trend toward lower AIRg ( 294.9 + /- 50.0 vs. 305.4 + /- 30.0 pmol/l ; P = 0.06 ) and incAUCg ( 8,217.3 + /- 350.7 vs. 8,902.0 + /- 367.2 mg . dl(-1 ) . 2 h(-1 ) ; P = 0.08 ) compared with the Step 1/stretching group after adjusting for baseline values . There was no difference in the DI ( P = 0.7 ) between the groups . S(i ) was associated with changes in weight ( r = -0.426 , P = 0.001 ) and IAF ( r = -0.395 , P = 0.003 ) and SCF ( r = -0.341 , P = 0.01 ) areas . Thus , the lifestyle modifications decreased weight and central adiposity and improved insulin sensitivity in Japanese Americans with IGT . However , such changes did not improve beta-cell function , suggesting that this degree of lifestyle modifications may be limited in preventing type 2 diabetes over the long term Prevention of type 2 diabetes by intensive lifestyle intervention design ed to achieve and maintain ideal body weight was assessed in subjects with impaired glucose tolerance ( IGT ) . Male subjects with IGT recruited from health-screening examinees were r and omly assigned in a 4:1 ratio to a st and ard intervention group ( control group ) and intensive intervention group ( intervention group ) . The final numbers of subjects were 356 and 102 , respectively . The subjects in the control group and in the intervention group were advised to maintain body mass index ( BMI ) of < 24.0 kg/m2 and of < 22.0 kg/m2 , respectively , by diet and exercise . In the intervention group , detailed instructions on lifestyle were repeated every 3 - 4 months during hospital visits . Diabetes was judged to have developed when two or more consecutive fasting plasma glucose ( FPG ) values exceeded 140 mg/dl . A 100 g oral glucose tolerance test was performed every 6 months to detect improvement of glucose tolerance . The subjects were seen in an ordinary outpatient clinic . The cumulative 4-year incidence of diabetes was 9.3 % in the control group , versus 3.0 % in the intervention group , and the reduction in risk of diabetes was 67.4 % ( P < 0.001 ) . Body weight decreased by 0.39 kg in the control group and by 2.18 kg in the intervention group ( P < 0.001 ) . The control group was subclassified according to increase and decrease in body weight . The incidence of diabetes was positively correlated with the changes in body weight , and the improvement in glucose tolerance was negatively correlated . Subjects with higher FPG at baseline developed diabetes at a higher rate than those with lower FPG . Higher 2h plasma glucose values and higher BMI values at baseline were also associated with a higher incidence of diabetes , but the differences were not significant . Subjects with a low insulinogenic index ( DeltaIRI/DeltaPG 30 min after an oral glucose load ) developed diabetes at a significantly higher rate than those with a normal insulinogenic index . Comparison of the BMI data and incidence of diabetes in five diabetes prevention studies by lifestyle intervention revealed a linear correlation between the incidence of diabetes and the BMI values , with the exception of the DaQing Study . However , the slope of the reduction in incidence of diabetes in the intensive intervention groups was steeper than expected simply on the basis of the reduction of BMI , suggesting that the effect of lifestyle intervention can not be solely ascribed to the body weight reduction . We conclude that lifestyle intervention aim ed at achieving ideal body weight in men with IGT is effective and can be conducted in an outpatient clinic setting Risk factors associated with the progression from impaired glucose tolerance ( IGT ) to NIDDM were examined in data from six prospect i ve studies . IGT and NIDDM were defined in all studies by World Health Organization ( WHO ) criteria , and baseline risk factors were measured at the time of first recognition of IGT . The studies varied in size from 177 to 693 participants with IGT , and included men and women followed from 2 to 27 years after the recognition of IGT . Across the six studies , the incidence rate of NIDDM was 57.2/1,000 person-years and ranged from 35.8/1,000 to 87.3/1,000 person-years . Although baseline measures of fasting and 2-h postchallenge glucose levels were both positively associated with NIDDM incidence , incidence rates were sharply higher for those in the top quartile of fasting plasma glucose levels , but increased linearly with increasing 2-h postchallenge glucose quartiles . Incidence rates were higher among the Hispanic , Mexican-American , Pima , and Nauruan population s than among Caucasians . The effect of baseline age on NIDDM incidence rates differed among the studies ; the rates did not increase or rose only slightly with increasing baseline age in three of the studies and formed an inverted U in three studies . In all studies , estimates of obesity ( including BMI , waist-to-hip ratio , and waist circumference ) were positively associated with NIDDM incidence . BMI was associated with NIDDM incidence independently of fasting and 2-h post challenge glucose levels in the combined analysis of all six studies and in three cohorts separately , but not in the three studies with the highest NIDDM incidence rates . Sex and family history of diabetes were generally not related to NIDDM progression . This analysis indicates that persons with IGT are at high risk and that further refinement of risk can be made by other simple measurements . The ability to identify persons at high risk of NIDDM should facilitate clinical trials in diabetes prevention The aim of the Finnish Diabetes Prevention Study is to assess the efficacy of an intensive diet-exercise programme in preventing or delaying type 2 diabetes in individuals with impaired glucose tolerance ( IGT ) and to evaluate the effect of the programme on the risk factors of atherosclerotic vascular diseases and the incidence of cardiovascular events . In this ongoing study , a total of 523 overweight subjects with IGT based on two oral glucose tolerance tests were r and omized to either an intervention group or a control group . The main measure in the intervention group is individual dietary advice aim ed at reducing weight and intake of saturated fat and increasing intake of dietary fibre . The intervention subjects are individually guided to increase their level of physical activity . The control group receives general information about the benefits of weight reduction , physical activity and healthy diet in the prevention of diabetes . A pilot study began in 1993 , and recruitment ended in 1998 . By the end of April 1999 there were 65 new cases of diabetes , 34 drop-outs and one death . The weight reduction was greater ( -4.6 kg ) at 1 year in the intervention group ( n = 152 ) than in the control group ( n = 143 , -0.9 kg , P < 0.0001 ) , and this difference was sustained in the second year of follow-up . At 1 year 43.4 % and at 2 years 41.8 % of the intervention subjects had achieved a weight reduction of at least 5 kg , while the corresponding figures for the control subjects were 14.0 and 12.0 % ( P < 0.001 between the groups ) . At 1 year the intervention group showed significantly greater reductions in 2 h glucose , fasting and 2 h insulin , systolic and diastolic blood pressure , and serum triglycerides . Most of the beneficial changes in cardiovascular risk factors were sustained for 2 years . These interim results of the ongoing Finnish Diabetes Prevention Study demonstrate the efficacy and feasibility of the lifestyle intervention programme OBJECTIVE To describe the 1 ) lifestyle intervention used in the Finnish Diabetes Prevention Study , 2 ) short- and long-term changes in diet and exercise behavior , and 3 ) effect of the intervention on glucose and lipid metabolism . RESEARCH DESIGN AND METHODS There were 522 middle-aged , overweight subjects with impaired glucose tolerance who were r and omized to either a usual care control group or an intensive lifestyle intervention group . The control group received general dietary and exercise advice at baseline and had an annual physician 's examination . The subjects in the intervention group received additional individualized dietary counseling from a nutritionist . They were also offered circuit-type resistance training sessions and advised to increase overall physical activity . The intervention was the most intensive during the first year , followed by a maintenance period . The intervention goals were to reduce body weight , reduce dietary and saturated fat , and increase physical activity and dietary fiber . RESULTS The intervention group showed significantly greater improvement in each intervention goal . After 1 and 3 years , weight reductions were 4.5 and 3.5 kg in the intervention group and 1.0 and 0.9 kg in the control group , respectively . Measures of glycemia and lipemia improved more in the intervention group . CONCLUSIONS The intensive lifestyle intervention produced long-term beneficial changes in diet , physical activity , and clinical and biochemical parameters and reduced diabetes risk . This type of intervention is a feasible option to prevent type 2 diabetes and should be implemented in the primary health care system Clinical trials have demonstrated that lifestyle changes can prevent type 2 diabetes , but the importance of leisure-time physical activity ( LTPA ) is still unclear . We carried out post hoc analyses on the role of LTPA in preventing type 2 diabetes in 487 men and women with impaired glucose tolerance who had completed 12-month LTPA question naires . The subjects were participants in the Finnish Diabetes Prevention Study , a r and omized controlled trial of lifestyle changes including diet , weight loss , and LTPA . There were 107 new cases of diabetes during the 4.1-year follow-up period . Individuals who increased moderate-to-vigorous LTPA or strenuous , structured LTPA the most were 63 - 65 % less likely to develop diabetes . Adjustment for changes in diet and body weight during the study attenuated the association somewhat ( upper versus lower third : moderate-to-vigorous LTPA , relative risk 0.51 , 95 % CI 0.26 - 0.97 ; strenuous , structured LTPA , 0.63 , 0.35 - 1.13 ) . Low-intensity and lifestyle LTPA and walking also conferred benefits , consistent with the finding that the change in total LTPA ( upper versus lower third : 0.34 , 0.19 - 0.62 ) was the most strongly associated with incident diabetes . Thus increasing physical activity may substantially reduce the incidence of type 2 diabetes in high-risk individuals BACKGROUND Type 2 diabetes mellitus is increasingly common , primarily because of increases in the prevalence of a sedentary lifestyle and obesity . Whether type 2 diabetes can be prevented by interventions that affect the lifestyles of subjects at high risk for the disease is not known . METHODS We r and omly assigned 522 middle-aged , overweight subjects ( 172 men and 350 women ; mean age , 55 years ; mean body-mass index [ weight in kilograms divided by the square of the height in meters ] , 31 ) with impaired glucose tolerance to either the intervention group or the control group . Each subject in the intervention group received individualized counseling aim ed at reducing weight , total intake of fat , and intake of saturated fat and increasing intake of fiber and physical activity . An oral glucose-tolerance test was performed annually ; the diagnosis of diabetes was confirmed by a second test . The mean duration of follow-up was 3.2 years . RESULTS The mean ( + /-SD ) amount of weight lost between base line and the end of year 1 was 4.2+/-5.1 kg in the intervention group and 0.8+/-3.7 kg in the control group ; the net loss by the end of year 2 was 3.5+/-5.5 kg in the intervention group and 0.8+/-4.4 kg in the control group ( P<0.001 for both comparisons between the groups ) . The cumulative incidence of diabetes after four years was 11 percent ( 95 percent confidence interval , 6 to 15 percent ) in the intervention group and 23 percent ( 95 percent confidence interval , 17 to 29 percent ) in the control group . During the trial , the risk of diabetes was reduced by 58 percent ( P<0.001 ) in the intervention group . The reduction in the incidence of diabetes was directly associated with changes in lifestyle . CONCLUSIONS Type 2 diabetes can be prevented by changes in the lifestyles of high-risk subjects Aims /hypothesisLifestyle modification helps in the primary prevention of diabetes in multiethnic American , Finnish and Chinese population s. In a prospect i ve community-based study , we tested whether the progression to diabetes could be influenced by interventions in native Asian Indians with IGT who were younger , leaner and more insulin resistant than the above population s. Methods We r and omised 531 ( 421 men 110 women ) subjects with IGT ( mean age 45.9±5.7 years , BMI 25.8±3.5 kg/m2 ) into four groups . Group 1 was the control , Group 2 was given advice on lifestyle modification ( LSM ) , Group 3 was treated with metformin ( MET ) and Group 4 was given LSM plus MET . The primary outcome measure was type 2 diabetes as diagnosed using World Health Organization criteria . Results The median follow-up period was 30 months , and the 3-year cumulative incidences of diabetes were 55.0 % , 39.3 % , 40.5 % and 39.5 % in Groups 1–4 , respectively . The relative risk reduction was 28.5 % with LSM ( 95 % CI 20.5–37.3 , p=0.018 ) , 26.4 % with MET ( 95 % CI 19.1–35.1 , p=0.029 ) and 28.2 % with LSM + MET ( 95 % CI 20.3–37.0 , p=0.022 ) , as compared with the control group . The number needed to treat to prevent one incident case of diabetes was 6.4 for LSM , 6.9 for MET and 6.5 for LSM + MET . Conclusions /interpretationProgression of IGT to diabetes is high in native Asian Indians . Both LSM and MET significantly reduced the incidence of diabetes in Asian Indians with IGT ; there was no added benefit from combining them OBJECTIVE To assess the effects of lifestyle intervention on cardiovascular risk factors in general and especially on fibrinolysis . DESIGN R and omized clinical study . SUBJECTS A total of 186 subjects with impaired glucose tolerance and obesity . INTERVENTIONS The intervention programme included a low-fat , high-fibre diet and regular physical exercise . Half of the participants ( n = 93 ) took part in a one-month learning and training session using different behavioural modification techniques and conducted in a full-board wellness centre ( intense intervention group ) . The other half ( n = 93 ) was r and omized a one-hour counselling session with a specially trained nurse ( usual care group ) . Follow-up was carried out after 12 months . MAIN OUTCOME MEASURES Body weight , oxygen consumption , plasminogen activator inhibitor type 1 ( PAI-1 ) activity , tissue plasminogen activator ( tPA ) antigen , fibrinogen and fasting plasma insulin measured at the start of the programme and at follow-up after 1 year . RESULTS The intense intervention group had a mean weight decline by 1 year of 5.4 kg compared to 0.5 kg in the usual care group . Oxygen consumption in the intense group increased 10 % vs. a 1 % decline in the usual care group . In the intense group , PAI-1 activity decreased 31 % ( -10.1 U mL(-1 ) ) , which was significantly more than in the usual care group ( 12 % ; -3.0 U mL(-1 ) ) . The corresponding reductions in tPA antigen were 14 % ( -1.65 microg L(-1 ) ) and 6 % ( -0.69 microg L(-1 ) ) . CONCLUSIONS The present r and omized study shows that an intense lifestyle programme has sustained beneficial effects on fibrinolysis Summary From a previously reported 5-year screening programme of 6,956 47–49-year-old Malmö males , a series of 41 subjects with early-stage Type 2 ( non-insulin-dependent ) diabetes mellitus and 181 subjects with impaired glucose tolerance were selected for prospect i ve study and to test the feasibility aspect of long-term intervention with an emphasis on life-style changes . A 5-year protocol , including an initial 6-months ( r and omised ) pilot study , consisting of dietary treatment and /or increase of physical activity or training with annual check-ups , was completed by 90 % of subjects . Body weight was reduced by 2.3–3.7 % among participants , whereas values increased by 0.5–1.7 % in non-intervened subjects with impaired glucose tolerance and in normal control subjects ( p<0.0001 ) ; maximal oxygen uptake ( ml · min−1 · kg−1 ) was increased by 10–14 % vs decreased by 5–9 % , respectively ( p<0.0001 ) . Glucose tolerance was normalized in > 50 % of subjects with impaired glucose tolerance , the accumulated incidence of diabetes was 10.6 % , and more than 50 % of the diabetic patients were in remission after a mean follow-up of 6 years . Blood pressure , lipids , and hyperinsulinaemia were reduced and early insulin responsiveness to glucose loading preserved . Improvement in glucose tolerance was correlated to weight reduction ( r=0.19 , p<0.02 ) and increased fitness ( r=0.22 , p<0.02 ) . Treatment was safe , and mortality was low ( in fact 33 % lower than in the remainder of the cohort ) . We conclude that long-term intervention in the form of diet and physical exercise is feasible even on a large scale , and that substantial metabolic improvement can be achieved which may contribute to prevent or postpone manifest diabetes OBJECTIVE To examine prospect ively the association between regular exercise and the subsequent development of non-insulin-dependent diabetes mellitus ( NIDDM ) . DESIGN Prospect i ve cohort study including 5 years of follow-up . PARTICIPANTS 21,271 US male physicians participating in the Physicians ' Health Study , aged 40 to 84 years and free of diagnosed diabetes mellitus , myocardial infa rct ion , cerebrovascular disease , and cancer at baseline . Morbidity follow-up was 99.7 % complete . MAIN OUTCOME MEASURE Incidence of NIDDM . RESULTS At baseline , information was obtained about frequency of vigorous exercise and other risk indicators . During 105,141 person-years of follow-up , 285 new cases of NIDDM were reported . The age-adjusted incidence of NIDDM ranged from 369 cases per 100,000 person-years in men who engaged in vigorous exercise less than once weekly to 214 cases per 100,000 person-years in those exercising at least five times per week ( P , trend , less than .001 ) . Men who exercised at least once per week had an age-adjusted relative risk ( RR ) of NIDDM of 0.64 ( 95 % Cl , 0.51 to 0.82 ; P = .0003 ) compared with those who exercised less frequently . The age-adjusted RR of NIDDM decreased with increasing frequency of exercise : 0.77 for once weekly , 0.62 for two to four times per week , and 0.58 for five or more times per week ( P , trend , .0002 ) . A significant reduction in risk of NIDDM persisted after adjustment for both age and body-mass index : RR , 0.71 ( 95 % Cl , 0.56 to 0.91 ; P = .006 ) for at least once per week compared with less than once weekly , and P , trend , .009 , for increasing frequency of exercise . Further control for smoking , hypertension , and other coronary risk factors did not material ly alter these associations . The inverse relation of exercise to risk of NIDDM was particularly pronounced among overweight men . CONCLUSIONS Exercise appears to reduce the development of NIDDM even after adjusting for body-mass index . Increased physical activity may be a promising approach to the primary prevention of NIDDM AIMS : Important risk factors for the progression from impaired glucose tolerance to type II diabetes mellitus are obesity , diet and physical inactivity . The aim of this study is to evaluate the effect of a lifestyle-intervention programme on glucose tolerance in Dutch subjects with impaired glucose tolerance ( IGT ) . METHODS : A total of 102 subjects were studied , r and omised into two groups . Subjects in the intervention group received regular dietary advice , and were stimulated to lose weight and to increase their physical activity . The control group received only brief information about the beneficial effects of a healthy diet and increased physical activity . Before and after the first year , glucose tolerance was measured and several other measurements were done . RESULTS : Body weight loss after 1 y was higher in the intervention group . The 2-h blood glucose concentration decreased 0.8±0.3 mmol/l in the intervention group and increased 0.2±0.3 mmol/l in the control group ( P<0.05 ) . Body weight loss and increased physical fitness were the most important determinants of improved glucose tolerance and insulin sensitivity . CONCLUSION : A lifestyle-intervention programme according to general recommendations is effective and induces beneficial changes in lifestyle , which improve glucose tolerance in subjects with IGT . Body weight loss and increased physical fitness were the most important determinants of improved glucose tolerance and insulin sensitivity OBJECTIVE Individuals with impaired glucose tolerance ( IGT ) have a high risk of developing NIDDM . The purpose of this study was to determine whether diet and exercise interventions in those with IGT may delay the development of NIDDM , i.e. , reduce the incidence of NIDDM , and thereby reduce the overall incidence of diabetic complications , such as cardiovascular , renal , and retinal disease , and the excess mortality attributable to these complications . RESEARCH DESIGN AND METHODS In 1986 , 110,660 men and women from 33 health care clinics in the city of Da Qing , China , were screened for IGT and NIDDM . Of these individuals , 577 were classified ( using World Health Organization criteria ) as having IGT . Subjects were r and omized by clinic into a clinical trial , either to a control group or to one of three active treatment groups : diet only , exercise only , or diet plus exercise . Follow-up evaluation examinations were conducted at 2-year intervals over a 6-year period to identify subjects who developed NIDDM . Cox 's proportional hazard analysis was used to determine if the incidence of NIDDM varied by treatment assignment . RESULTS The cumulative incidence of diabetes at 6 years was 67.7 % ( 95 % CI , 59.8–75.2 ) in the control group compared with 43.8 % ( 95 % CI , 35.5–52.3 ) in the diet group , 41.1 % ( 95 % CI , 33.4–49.4 ) in the exercise group , and 46.0 % ( 95 % CI , 37.3–54.7 ) in the diet-plus-exercise group ( P < 0.05 ) . When analyzed by clinic , each of the active intervention groups differed significantly from the control clinics ( P < 0.05 ) . The relative decrease in rate of development of diabetes in the active treatment groups was similar when subjects were stratified as lean or overweight ( BMI < or ≥ 25 kg/m2 ) . In a proportional hazards analysis adjusted for differences in baseline BMI and fasting glucose , the diet , exercise , and diet-plus-exercise interventions were associated with 31 % ( P < 0.03 ) , 46 % ( P < 0.0005 ) , and 42 % ( P < 0.005 ) reductions in risk of developing diabetes , respectively . CONCLUSIONS Diet and /or exercise interventions led to a significant decrease in the incidence of diabetes over a 6-year period among those with IGT BACKGROUND Type 2 diabetes affects approximately 8 percent of adults in the United States . Some risk factors -- elevated plasma glucose concentrations in the fasting state and after an oral glucose load , overweight , and a sedentary lifestyle -- are potentially reversible . We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes . METHODS We r and omly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo , metformin ( 850 mg twice daily ) , or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week . The mean age of the participants was 51 years , and the mean body-mass index ( the weight in kilograms divided by the square of the height in meters ) was 34.0 ; 68 percent were women , and 45 percent were members of minority groups . RESULTS The average follow-up was 2.8 years . The incidence of diabetes was 11.0 , 7.8 , and 4.8 cases per 100 person-years in the placebo , metformin , and lifestyle groups , respectively . The lifestyle intervention reduced the incidence by 58 percent ( 95 percent confidence interval , 48 to 66 percent ) and metformin by 31 percent ( 95 percent confidence interval , 17 to 43 percent ) , as compared with placebo ; the lifestyle intervention was significantly more effective than metformin . To prevent one case of diabetes during a period of three years , 6.9 persons would have to participate in the lifestyle-intervention program , and 13.9 would have to receive metformin . CONCLUSIONS Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk . The lifestyle intervention was more effective than metformin For decades , exercise has been considered a cornerstone of diabetes management , along with diet and medication . However , high- quality evidence on the importance of exercise and fitness in diabetes was lacking until recent years . The present document summarizes the most clinical ly relevant recent advances related to people with type 2 diabetes and the recommendations that follow from these . Our recently published technical review on physical activity/exercise and type 2 diabetes ( 1 ) includes greater detail on individual studies , on prevention of diabetes , and on the physiology of exercise . The present statement focuses on type 2 diabetes . Issues primarily germane to type 1 diabetes will be covered in a subsequent technical review and ADA Statement . The levels of evidence used are defined by the ADA in ref . 2 . Two r and omized trials each found that lifestyle interventions including ∼150 min/week of physical activity and diet-induced weight loss of 5–7 % reduced the risk of progression from impaired glucose tolerance ( IGT ) to type 2 diabetes by 58 % ( 3,4 ) . A cluster-r and omized trial found that diet alone , exercise alone , and combined diet and exercise were equally effective in reducting the progression from IGT to diabetes ( 5 ) . Therefore , there is firm and consistent evidence that programs of increased physical activity and modest weight loss reduce the incidence of type 2 diabetes in individuals with IGT . Boule et al. ( 6 ) undertook a systematic review and meta- analysis on the effects of structured exercise interventions in clinical trials of ≥8 weeks duration on HbA1c ( A1C ) and body mass in people with type 2 diabetes . Postintervention A1C was significantly lower in exercise than control groups ( 7.65 vs. 8.31 % , weighted mean difference −0.66 % ; P < 0.001 ) . In contrast , postintervention body weight did not differ between the exercise and control groups . Meta-regression confirmed that the beneficial effect of exercise on A1C The Paris Prospect i ve Study is a long-term investigation of cardiovascular diseases in a population of 7164 working men , aged 43 - 54 years . The first annual follow-up session ( 1968 - 73 ) included a 0 - 2 hr 75 g OGTT with measurement of plasma insulin and glucose levels beside the major coronary heart disease ( CHD ) risk factors : arterial pressure , cigarette smoking , weight , cholesterol , triglycerides . After a mean 11.2 years follow-up , 651 deaths , among them 126 due to CHD , were recorded . The annual CHD mortality rates were respectively 1.4 , 2.7 and 3.2 per 1000 for the 6055 normoglycaemic , 690 impaired glucose tolerance , and 293 new and known diabetic subjects ( 1980 WHO classification ) ( p less than 0.01 ) . The annual risk was analyzed by the multivariate Cox model . It showed that the fasting plasma insulin was positively associated with risk independent of the other factors ( p less than 0.05 ) , whereas glucose tolerance , including overt diabetes , was not significantly associated . We conclude that high insulin levels may constitute a more sensitive predictor of CHD than the degree of glucose intolerance , it could be useful to avoid excessive insulin plasma concentration , and even to lower its level AIM To evaluate the effectiveness of lifestyle interventions in people with impaired glucose tolerance ( IGT ) . METHODS Participants with IGT ( n=78 ) , diagnosed on two consecutive oral glucose tolerance tests ( OGTTs ) , were r and omly assigned to a 2-year lifestyle intervention or to a control group . Main outcome measures were changes from baseline in : nutrient intake ; physical activity ; anthropometry , glucose tolerance and insulin sensitivity . Measurements were repeated at 6 , 12 and 24 months follow-up . RESULTS After 24 months follow-up , there was a significant fall in total fat consumption ( difference in change between groups ( Delta intervention-Delta control)= -17.9 , 95 % confidence interval ( CI ) -33.6 to -2.1g/day ) as a result of the intervention . Body mass was significantly lower in the intervention group compared with controls after 6 months ( -1.6 , 95 % CI -2.9 to -0.4 kg ) and 24 months ( -3.3 , 95 % CI -5.7 to -0.89 kg ) . Whole body insulin sensitivity , assessed by the short insulin tolerance test ( ITT ) , improved after 12 months in the intervention group ( 0.52 , 95 % CI 0.15 - 0.89%/min ) . CONCLUSIONS These findings complement the findings of the Finnish Diabetes Prevention Study and the American Diabetes Prevention Study , both of which tested intensive interventions , by showing that pragmatic lifestyle interventions result in improvements in obesity and whole body insulin sensitivity in individuals with IGT , without change in other cardiovascular risk factors |
1,253 | 28,177,474 | Overall , no evidence was found favoring a particular intervention strategy .
Conclusion : Due to few high quality studies , evidence for the effectiveness of any particular intervention strategy to stimulate healthy sleep in children is still inconclusive .
However , the more effective interventions in stimulating healthy sleep duration and adherence to regular bedtimes were mostly multi-behavioral interventions that included creating daily healthy routines and combined intervention setting s ( e.g. home and school ) . | Background : Healthy sleep among children has social , physical and mental health benefits .
As most of today ’s children do not meet the healthy sleep recommendations , effective interventions are urgently needed .
This systematic review summarizes the characteristics and effectiveness of interventions aim ing to stimulate healthy sleeping in a general population of school-aged children . | Background The current study aim ed to examine the changes following a sleep hygiene intervention on sleep hygiene practice s , sleep quality , and daytime symptoms in youth . Methods Participants aged 10–18 years with self-identified sleep problems completed our age-appropriate F.E.R.R.E.T ( an acronym for the categories of Food , Emotions , Routine , Restrict , Environment and Timing ) sleep hygiene programme ; each category has three simple rules to encourage good sleep . Participants ( and parents as appropriate ) completed the Adolescent Sleep Hygiene Scale ( ASHS ) , Pittsburgh Sleep Quality Index ( PSQI ) , Sleep Disturbance Scale for Children ( SDSC ) , Pediatric Daytime Sleepiness Scale ( PDSS ) , and wore Actical ® monitors twice before ( 1 and 2 weeks ) and three times after ( 6 , 12 and 20 weeks ) the intervention . Anthropometric data were collected two weeks before and 20 weeks post-intervention . Results Thirty-three youths ( mean age 12.9 years ; M/F = 0.8 ) enrolled , and retention was 100 % . ASHS scores significantly improved ( p = 0.005 ) from a baseline mean ( SD ) of 4.70 ( 0.41 ) to 4.95 ( 0.31 ) post-intervention , as did PSQI scores [ 7.47 ( 2.43 ) to 4.47 ( 2.37 ) ; p < 0.001 ] and SDSC scores [ 53.4 ( 9.0 ) to 39.2 ( 9.2 ) ; p < 0.001 ] . PDSS scores improved from a baseline of 16.5 ( 6.0 ) to 11.3 ( 6.0 ) post- intervention ( p < 0.001 ) . BMI z-scores with a baseline of 0.79 ( 1.18 ) decreased significantly ( p = 0.001 ) post-intervention to 0.66 ( 1.19 ) . Despite these improvements , sleep duration as estimated by Actical accelerometry did not change . There was however a significant decrease in daytime sedentary/light energy expenditure . Conclusions Our findings suggest the F.E.R.R.E.T sleep hygiene education programme might be effective in improving sleep in children and adolescents . However because this was a before and after study and a pilot study with several limitations , the findings need to be addressed with caution , and would need to be replicated within a r and omised controlled trial to prove efficacy . Trial registration Australian New Zeal and Clinical Trials Registry : Background Sufficient sleep during childhood is essential to ensure a transition into a healthy adulthood . However , chronic sleep loss continues to increase worldwide . In this context , it is imperative to make sleep a high-priority and take action to promote sleep health among children . The present series of studies aim ed to shed light on sleep patterns , on the longitudinal association of sleep with school performance , and on practical intervention strategy for Chinese school-aged children . Methods and Findings A serial sleep research es , including a national cross-sectional survey , a prospect i ve cohort study , and a school-based sleep intervention , were conducted in China from November 2005 through December 2009 . The national cross-sectional survey was conducted in 8 cities and a r and om sample of 20,778 children aged 9.0±1.61 years participated in the survey . The five-year prospect i ve cohort study included 612 children aged 6.8±0.31 years . The comparative cross-sectional study ( baseline : n = 525 , aged 10.80±0.41 ; post-intervention follow-up : n = 553 , aged 10.81±0.33 ) was undertaken in 6 primary schools in Shanghai . A battery of parent and teacher reported question naires were used to collect information on children ’s sleep behaviors , school performance , and sociodemographic characteristics . The mean sleep duration was 9.35±0.77 hours . The prevalence of daytime sleepiness was 64.4 % ( sometimes : 37.50 % ; frequently : 26.94 % ) . Daytime sleepiness was significantly associated with impaired attention , learning motivation , and particularly , academic achievement . By contrast , short sleep duration only related to impaired academic achievement . After delaying school start time 30 minutes and 60 minutes , respectively , sleep duration correspondingly increased by 15.6 minutes and 22.8 minutes , respectively . Moreover , intervention significantly improved the sleep duration and daytime sleepiness . Conclusions Insufficient sleep and daytime sleepiness commonly existed and positively associated with the impairment of school performance , especially academic achievement , among Chinese school-aged children . The effectiveness of delaying school staring time emphasized the benefits of optimal school schedule regulation to children ’s sleep health A total of 36 toddlers and preschool children exhibiting bedtime tantrum activity were r and omly assigned to one of three groups : positive routines , graduated extinction , or control . Positive routines involved changing the child 's bedtime to coincide with when he naturally fell asleep , as well as parent and child engaging in a series of four to seven enjoyable activities before the child being placed in bed . During the treatment period , bedtimes were systematic ally scheduled earlier such that the child went to bed at the time parents had originally used . Graduated extinction consisted of the parent putting the child to bed and ignoring the tantrum activity for increasingly longer amounts of time throughout the treatment . Children in these two treatment groups had tantrums less frequently and for shorter periods than control subjects during 6 weeks of treatment and during two follow-up observations 3 and 6 weeks after treatment . Although both treatments were more effective than waiting for the child to outgrow this problem , parents of the positive routine group reported significantly improved marital satisfaction , suggesting additional benefits of this treatment strategy Abstract ObjectiveS leep deprivation among teens is a major health issue . Only 15 % of teens get 8.5 h of sleep on school nights . Sleep deprivation can lead to poor grade s , sleepiness and moodiness . We undertook a study to assess the prevalence of sleep habit disturbance among elementary school students in South Texas with Hispanic ethnicity predominance . We also found how much a video based on sleep education had an impact on these children . Method Once the Corpus Christi Independent School District ( CCISD ) approved the collection of baseline sleep data , question naires were administered using the Children ’s Sleep Habit Question naire ( CSHQ . ) These question naires were distributed prior to the viewing of the educational and animated movie KNIGHTS ( Keep Nurturing and Inspiring Good Habits in Teen Sleep ) . Four months later , a r and om follow-up was performed and the children were requested to respond to the same CSHQ . Results 264 children from two elementary schools participated in this educational program . At baseline , 55.56 % of the children had trouble sleeping . When the question naire was administered four months later , only 23.26 % ( p < 0.05 ) had trouble sleeping . Additionally , at baseline , approximately 60–70 % children had some baseline bedtime resistance , anxiety dealing with sleep , issues with sleep duration and /or awakenings in the middle of the night . In the follow up question naire , results showed significant improvements in overall sleep habits , bedtime resistance , sleep anxiety and night awakenings amongst students ( p < 0.05 ) . However , no significant differences were seen in sleep duration and daytime sleepiness . ConclusionS leep deprivation and good sleep habits remain as a pervasive challenge among elementary school students . Administering an animated video about sleep education along with a provider-based education may be an effective tool for educating elementary school students and decreasing the prevalence of these sleep-related issues . Future prospect i ve r and omized studies are suggested PURPOSE The implication s of sleep patterns for adolescent health are well established , but we know less about larger context ual influences on youth sleep . We focused on parents ' workplace experiences as extrafamilial forces that may affect youth sleep . METHODS In a group-r and omized trial focused on employee work groups in the information technology division of a Fortune 500 company , we tested whether a workplace intervention improved sleep latency , duration , night-to-night variability in duration , and quality of sleep of employees ' offspring , aged 9 - 17 years . The intervention was aim ed at promoting employees ' schedule control and supervisor support for personal and family life to decrease employees ' work-family conflict and thereby promote the health of employees , their families , and the work organization . Analyses focused on 93 parent-adolescent dyads ( 57 dyads in the intervention and 46 in the comparison group ) that completed baseline and 12-month follow-up home interviews and a series of telephone diary interviews that were conducted on eight consecutive evenings at each wave . RESULTS Intent-to-treat analyses of the diary interview data revealed main effects of the intervention on youth 's sleep latency , night-to-night variability in sleep duration , and sleep quality , but not sleep duration . CONCLUSIONS The intervention focused on parents ' work conditions , not on their parenting or parent-child relationships , attesting to the role of larger context ual influences on youth sleep and the importance of parents ' work experiences in the health of their children BACKGROUND : Although observational studies have consistently reported an association between media use and child sleep problems , it is unclear whether the relationship is causal or if an intervention targeting healthy media use can improve sleep in preschool-aged children . METHODS : We conducted a r and omized controlled trial of a healthy media use intervention in families of children aged 3 to 5 years . The intervention encouraged families to replace violent or age-inappropriate media content with quality educational and prosocial content , through an initial home visit and follow-up telephone calls over 6 months . Sleep measures were derived from the Child Sleep Habits Question naire and were collected at 6 , 12 , and 18 months after baseline ; repeated- measures regression analyses were used . RESULTS : Among the 565 children analyzed , the most common sleep problem was delayed sleep-onset latency ( 38 % ) . Children in the intervention group had significantly lower odds of “ any sleep problem ” at follow-up in the repeated- measures analysis ( odds ratio = 0.36 ; 95 % confidence interval : 0.16 to 0.83 ) , with a trend toward a decrease in intervention effect over time ( P = .07 ) . Although there was no significant effect modification detected by baseline sleep or behavior problems , gender , or low-income status , there was a trend ( P = .096 ) toward an increased effect among those with high levels of violence exposure at baseline . CONCLUSIONS : The significant effects of a healthy media use intervention on child sleep problems in the context of a r and omized controlled trial suggest that the previously reported relationship between media use and child sleep problems is indeed causal in nature There is considerable research that suggests that school-based social – emotional programs can foster improved mental health and reduce problem behaviors for participating youth ; in contrast , much less is known about the impact of these programs on physical health , even though some of these programs also include at least limited direct attention to promoting physical health behaviors . We examined the effects of one such program , Positive Action ( PA ) , on physical health behaviors and body mass index ( BMI ) , and tested for mediation of program effects through a measure of social – emotional and character development ( SECD ) . Participating schools in the matched-pair , cluster-r and omized trial were 14 low-performing K-8 Chicago Public Schools . We followed a cohort of students in each school from grade s 3 to 8 ( eight waves of data collection ; 1170 total students ) . Student self-reports of health behaviors served as the basis for measures of healthy eating and exercise , unhealthy eating , personal hygiene , consistent bedtime , and SECD . We collected height and weight measurements at endpoint to calculate age- and gender-adjusted BMI z-scores . Longitudinal multilevel modeling analyses revealed evidence of favorable program effects on personal hygiene [ effect size ( ES ) = 0.48 ] , healthy eating and exercise ( ES = 0.21 ) , and unhealthy eating ( ES = −0.19 ) ; in addition , BMI z-scores were lower among students in PA schools at endpoint ( ES = −0.21 ) . Program effects were not moderated by either gender or student mobility . Longitudinal structural equation modeling demonstrated mediation through SECD for healthy eating and exercise , unhealthy eating , and personal hygiene . Findings suggest that a SECD program without a primary focus on health behavior promotion can have a modest impact on outcomes in this domain during the childhood to adolescence transition OBJECTIVE Sleep difficulties are common reasons why parents seek medical intervention in children with autism spectrum disorders ( ASDs ) . We determined whether a pamphlet alone could be used by parents to help their child ’s insomnia . METHODS Thirty-six children with ASD , ages 2 to 10 years , were enrolled . All had prolonged sleep latency confirmed by actigraphy showing a mean sleep latency of 30 minutes or more . Parents were r and omly assigned to receive the sleep education pamphlet or no intervention . Children wore an actigraphy device to record baseline sleep parameters , with the primary outcome variable being change in sleep latency . Actigraphy data were collected a second time 2 weeks after the parent received the r and omization assignment and analyzed by using Student ’s t test . Parents were also asked a series of questions to gather information about the pamphlet and its usefulness . RESULTS Although participants r and omized to the 2 arms did not differ statistically in age , gender , socioeconomic status , total Children ’s Sleep Habits Question naire score , or actigraphy parameters , some differences may be large enough to affect results . Mean change in sleep-onset latency did not differ between the r and omized groups ( pamphlet versus no pamphlet ) . Parents commented that the pamphlet contained good information , but indicated that it would have been more useful to be given specific examples of how to take the information and put it into practice . CONCLUSIONS A sleep education pamphlet did not appear to improve sleep latency in children with ASDs PURPOSE To investigate whether chronic vigorous exercising is related to improved sleep and psychological functioning , and whether this association varies with gender . Both lay and scientific opinions hold that physical activity is an efficient remedy and preventative measure for poor sleep . However , empirical evidence on adolescents is very limited . METHODS A total of 434 adolescents ( 258 athletes , 176 controls ; mean age 17.2 years ) took part in the study . Weekly hours spent exercising were 17.69 hours and 4.69 hours , respectively . To assess sleep patterns and psychological functioning , participants completed a sleep log for 7 consecutive days and several self-rating question naires . RESULTS Compared with controls , athletes reported better sleep patterns including higher sleep quality , shortened sleep onset latency , and fewer awakenings after sleep onset , as well as less tiredness and increased concentration during the day . Athletes reported significantly lower anxiety and fewer depressive symptoms . Compared with males , females reported fewer variations in sleep . Male controls had particularly unfavorable scores related to sleep and psychological functioning . CONCLUSIONS Findings suggest that chronic vigorous exercising is positively related to adolescents ' sleep and psychological functioning . Results also indicate that males with low exercise levels are at risk for increased sleep complaints and poorer psychological functioning STUDY OBJECTIVES To evaluate a novel sleep education program for low-income preschool children and their families . DESIGN R and omized trial of an educational intervention . SETTING Community-based . PARTICIPANTS Head Start preschool families ( n = 152 ) in greater Lansing and Detroit , Michigan . INTERVENTIONS Classrooms or Head Start sites were r and omized to an intervention group ( prompt intervention ) versus a control group ( delayed intervention ) . Parents attended a one-time , 45-min sleep education program and preschoolers received 2 w ( 320 total min ) of classroom sleep curriculum . MEASUREMENTS Parent knowledge , attitudes , self-efficacy , and beliefs were assessed as the primary outcomes just before the 45-min sleep intervention , immediately postintervention , and approximately 1 mo postintervention . Parents reported their child 's bedtimes and wake times on 7-day sleep diaries at baseline and at 1-mo follow-up . Average weeknight sleep duration s and bedtimes served as secondary outcomes . RESULTS Linear mixed models showed a time × treatment effect for parents ' knowledge , attitudes , and self-efficacy ( each P < 0.05 ) but not beliefs . These improvements were found immediately postintervention but were not retained at 1-mo follow-up . Children in the intervention group improved their weeknight sleep duration at 1-mo follow-up by 30 min ( 11.0 ± 0.9 h vs. 10.5 ± 1.0 hours at baseline ) compared to controls ( 10.4 ± 0.9 h versus 10.5 ± 0.9 h at baseline ) ( P = 0.04 for difference between groups ) . Children did not show statistically significant improvements in bedtime . CONCLUSIONS Educational interventions in early childhood can have an effect on parents ' sleep knowledge , attitudes , and self-efficacy , and on children 's sleep behavior . However , repeated exposure to the new information may be important for parents as well as their children The aims of this study were to document time-related ( morning versus afternoon ) effects of physical activities ( gymnastics ) on a set of physiological and psychological variables in school children , including diurnal changes . For the study , 61 boys and 69 girls , 6 to 11 years of age , volunteered . They were considered healthy according to routine clinical criteria . They were synchronized with diurnal activity from around 07:00 to 21:00 and nocturnal rest , time of year being taken into account . Tests were performed at school during 4 weeks of 4.5 days of school at fixed clock hours : 09:00 , 11:00 , 14:00 , and 16:00 . Gym time was r and omized with regard to week order and season . Four different classes ( 39 boys and 38 girls ) were involved in psychophysiological tests , and two different classes ( 22 boys and 31 girls ) collected saliva sample s for morning free cortisol determination . Both t-test and three-factor analysis of variance ( ANOVA ) were used for statistical analyses . Better performances were obtained in June than in mid-winter with reference to letter cancellation and r and om number addition tests . As a group phenomenon , morning ( 09:00 to 10:00 ) versus afternoon ( 14:00 to 15:00 ) gym was not an influential condition with regard to sleep duration , oral temperature , self-rated fatigue and drowsiness , letter cancellation , addition tests , or salivary cortisol . However , gym-time-related differences were observed in classes of younger subjects ( e.g. , 6 - 7 years ) with regard to self-rated fatigue and the letter cancellation test . Such variability among subgroups suggests that interindividual differences are likely to exist in younger children with regard to manipulation of environmental factors . In addition , gym itself ( without gym time consideration ) may be an influential factor with regard to diurnal patterns of some variables ( e.g. , the letter cancellation test ) 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 OBJECTIVE To assess the effectiveness of an intervention programme to improve kindergarten children 's eating and leisure habits in Israel . DESIGN A cluster-r and omised controlled trial . SETTING Six full-day kindergartens in Israel were r and omly divided into three groups . Group A received the full intervention programme , which included lessons on good eating habits and daily physical exercise . Group B received a partial intervention of lessons only . Group C , the reference group , did not receive any intervention . SUBJECTS Children aged 4 - 6 years ( n 204 ) were recruited for the study . METHODS Objective data for weight and height were collected to calculate BMI Z-scores . Activity , sedentary time , sleeping hours and daily energy intake were assessed via a parental question naire . Nutritional knowledge was assessed by a single dietitian using a question naire addressed to the children . Assessment s were done at baseline and at the end of the intervention . RESULTS After adjustment for baseline levels we observed a significant reduction in daily energy intake for the full intervention group A ( P = 0.03 ) . A positive intervention effect was demonstrated on nutritional knowledge in the partial intervention group B ( P = 0.03 ) , although no significant change was demonstrated for BMI Z-score . CONCLUSIONS The study supports the incorporation of education on healthy lifestyle habits and physical activity into the curricula of kindergartens OBJECTIVE : To assess the effectiveness of a weighted-blanket intervention in treating severe sleep problems in children with autism spectrum disorder ( ASD ) . METHODS : This phase III trial was a r and omized , placebo-controlled crossover design . Participants were aged between 5 years and 16 years 10 months , with a confirmed ASD diagnosis and severe sleep problems , refractory to community-based interventions . The interventions were either a commercially available weighted blanket or otherwise identical usual weight blanket ( control ) , introduced at bedtime ; each was used for a 2-week period before crossover to the other blanket . Primary outcome was total sleep time ( TST ) recorded by actigraphy over each 2-week period . Secondary outcomes included actigraphically recorded sleep-onset latency , sleep efficiency , assessment s of child behavior , family functioning , and adverse events . Sleep was also measured by using parent-report diaries . RESULTS : Seventy-three children were r and omized and analysis conducted on 67 children who completed the study . Using objective measures , the weighted blanket , compared with the control blanket , did not increase TST as measured by actigraphy and adjusted for baseline TST . There were no group differences in any other objective or subjective measure of sleep , including behavioral outcomes . On subjective preference measures , parents and children favored the weighted blanket . CONCLUSIONS : The use of a weighted blanket did not help children with ASD sleep for a longer period of time , fall asleep significantly faster , or wake less often . However , the weighted blanket was favored by children and parents , and blankets were well tolerated over this period IMPORTANCE Racial/ethnic and socioeconomic disparities exist across risk factors for childhood obesity . OBJECTIVE To examine the effectiveness of a home-based intervention to improve household routines known to be associated with childhood obesity among a sample of low-income , racial/ethnic minority families with young children . DESIGN R and omized trial . SETTING The intervention was delivered in the families ' homes . PARTICIPANTS The study involved 121 families with children aged 2 to 5 years who had a television ( TV ) in the room where he or she slept ; 111 ( 92 % ) had 6-month outcome data ( 55 intervention and 56 control ) . The mean ( SD ) age of the children was 4.0 ( 1.1 ) years ; 45 % were overweight/obese . Fifty-two percent of the children were Hispanic , 34 % were black , and 14 % were white/other . Nearly 60 % of the families had household incomes of $ 20,000 or less . INTERVENTIONS The 6-month intervention promoted 4 household routines , family meals , adequate sleep , limiting TV time , and removing the TV from the child 's bedroom , using ( 1 ) motivational coaching at home and by phone , ( 2 ) mailed educational material s , and ( 3 ) text messages . Control subjects were mailed material s focused on child development . MAIN OUTCOMES AND MEASURES Change in parent report of frequency of family meals ( times/wk ) , child sleep duration ( hours/d ) , child weekday and weekend day TV viewing ( hours/d ) , and the presence of a TV in the room where the child slept from baseline to 6 months . A secondary outcome was change in age- and sex-adjusted body mass index ( calculated as weight in kilograms divided by height in meters squared ) . RESULTS Compared with control subjects , intervention participants had increased sleep duration ( 0.75 hours/d ; 95 % CI , 0.06 to 1.44 ; P = .03 ) , greater decreases in TV viewing on weekend days ( -1.06 hours/d ; 95 % CI , -1.97 to -0.15 ; P = .02 ) , and decreased body mass index ( -0.40 ; 95 % CI , -0.79 to 0.00 ; P = .05 ) . No significant intervention effect was found for the presence of a TV in the room where the child slept or family meal frequency . CONCLUSIONS AND RELEVANCE Our results suggest that promoting household routines , particularly increasing sleep duration and reducing TV viewing , may be an effective approach to reduce body mass index among low-income , racial/ethnic minority children . Longer-term studies are needed to determine maintenance of behavior change . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01565161 OBJECTIVE The current study aim ed to develop and evaluate a motivational school-based intervention for adolescent sleep problems . METHODS The intervention was implemented in three co-educational secondary schools in Adelaide , South Australia . Two year-11 Psychology classes from each school participated , with one as the intervention class ( N=53 ) and one as the control class ( N=51 ) . Students in the intervention classes attended four 50-min sleep education classes , held once per week . The lessons were modified from those of Moseley and Gradisar [ 23 ] to incorporate a motivational interviewing framework . Students completed an online question naire battery measuring school day and weekend sleep parameters , daytime sleepiness , and depression at pre- and post-program and follow-up , and completed motivation to change question naires during the program . RESULTS Students in the intervention group significantly increased their knowledge about sleep relative to the control group ( p=0.001 ) . During the intervention , students ' motivation to regularize their out-of-bed times improved ( p=0.03 ) , and there was a trend towards improved motivation to increase average total sleep time ( p=0.11 ) . But despite improvements in sleep and daytime functioning for adolescents in the program group ( p<0.05 ) , these changes were not significantly different from the control group ( all p>0.05 ) . CONCLUSIONS School-based interventions are promising for educating adolescents about sleep . Future programs should translate increased motivation into long-term behavioral change . The identification of barriers and support to assist this change is recommended OBJECTIVES The present study investigated the effectiveness of a school-based sleep education programme in improving key sleep behaviours , sleep knowledge , and sleep hygiene . DESIGN AND METHODS A cross-sectional cluster-r and omised controlled trial with two groups ( Intervention and Control ) and three assessment time points [ baseline , immediately post intervention ( 6 weeks post baseline ) and follow-up ( 18 weeks post baseline ) ] was employed . A total of 296 students ( mean age = 12.2 ± 0.6 years ; 59 % female ) from 12 schools in Adelaide , South Australia , were recruited , with 149 participants in the Intervention group and 147 in the Control group . The intervention consisted of four classroom lessons delivered at weekly intervals , followed by a group project on sleep topics , which students presented at a parental information evening . Sleep patterns were assessed objective ly ( actigraphy , n = 175 ) and subjectively ( time-use recall , n = 251 ) at three time points . Sleep knowledge and sleep hygiene ( n = 296 ) were also measured . RESULTS Generalised estimating equations were used to compare changes in the Intervention and Control groups . The programme increased time in bed by 10 min ( p = 0.03 ) for the Intervention group relative to the Control group , due to a 10-min delay in wake time ( p = 0.00 ) . These changes were not sustained at follow-up . There was no impact on sleep knowledge or sleep hygiene . CONCLUSION Investment in the sleep health of youth through sleep education is important but changes to sleep patterns are difficult to achieve . More intensive programmes , programmes with a different focus or programmes targeting different age groups may be more effective |
1,254 | 10,613,641 | We conclude that there is no convincing evidence of either positively or negatively effects of UFH on survival of patients with malignancy | Clinical and experimental studies have suggested that unfractionated heparin ( UFH ) effects malignancy progression . | About half the patients treated with curative resection for colorectal cancer do not survive long-term . Adjuvant chemotherapy given during and after surgery may prevent hepatic metastases and improve patient survival . In patients with colorectal cancer , we have done a multicentre , r and omised controlled trial comparing five-year survival after intraportal infusion of fluorouracil ( 1 g per day ) plus heparin ( 10,000 U per day ) ( 130 patients ) or heparin alone ( 123 ) during curative resection and for 7 days thereafter , or after resection alone ( 145 ) . There was no reduction in liver metastasis or increased overall survival advantage in either active-treatment arm of the study . However , patients who had stage III , Dukes ' C ( lymph-node-positive ) tumours resected and were treated with fluorouracil plus heparin had a significant ( p less than 0.03 ) survival advantage of about 16 % compared with surgery-only controls . Further study of intraportal infusion of chemotherapeutic agent as adjuvant treatment to surgery in patients with colorectal cancer appears worthwhile In this phase III clinical trial conducted by the Gastrointestinal Tract Cancer Cooperative Group of the European Organization for Research and Treatment of Cancer ( GITCCG-EORTC ) , we evaluated the effect of adjuvant intraportal infusion of heparin ( HEP ) and 5-fluorouracil ( 5-FU ) on overall survival , disease-free survival and time to progression in patients with resectable colon cancer . From January 1983 to June 1987 , 235 patients were r and omised from 14 institutions in seven European countries : 79 patients made up the control group ( control ) : 72 the portal vein infusion group given heparin alone ( 5000 IU daily x 7 consecutive days ) ( HEP ) ; 84 the portal vein infusion group given heparin ( 5000 IU daily x 7 consecutive days ) and 5-FU ( 500 mg/m2 daily x 7 consecutive days ) ( HEP/5-FU ) ; 34 patients were considered ineligible . The 199 patients considered eligible were well balanced for age , sex , Karnofsky index , tumour location , surgery , surgical procedure and Dukes ' stage . Four patients ( 2 control , 1 HEP , 1 HEP/5-FU ) died of surgical complications . No differences were observed between control group and treatment groups ( HEP , HEP/5-FU ) for postoperative complications and number of hospitalisation days . Severe toxicity ( grade 3 - 4 , WHO ) was found in 12 % of patients in the HEP group and 8 % in the HEP/5-FU group . After a median follow-up of 9 years , disease progression was reported in 40 % of patients in the control group , 40 % in the HEP group and 29 % in the HEP/5-FU group . Five-year survival , time to progression and disease-free survival were 69 % , 58 % and 56 % , respectively , in the control arm , 61 % , 58 % and 56 % in the HEP arm , and 71 % , 69 % and 65 % in the HEP/5-FU arm . Based on all r and omised patients , the effect of treatment was not statistically significant with respect to any of the endpoints . It is confirmed that intraportal 5-FU infusion is safe and has a tolerable toxicity , but can not be considered st and ard treatment for patients with resectable colon cancer Background and Methods . Fifty‐one patients with small cell lung cancer ( SCLC ) were treated with alternating urokinase (UK)‐cyclophosphamide‐doxorubicin ( Adriamycin , Adria Laboratories , Columbus , OH)‐vincristine and cisplatin‐etoposide‐vincristine . UK was given as a loading dose of 3000 μg/kg body weight , followed by 3000 μg/kg/h for 6 hours . Thoracic irradiation with split technique ( 46 Gy ) and prophylactic cranial irradiation ( 25 Gy ) were administered to responding patients . A second staging was performed in patients exhibiting a clinical complete response ( CR ) after 1 year Background . A positive influence of anticoagulant treatment in small cell lung cancer ( SCLC ) has been sug gested by experimental and clinical data The Cancer and Leukemia Group B ( CALGB ) conducted a prospect i ve r and omized trial to evaluate the role of warfarin and alternating chemotherapy in extensive small-cell lung cancer ( SCCL ) . After stratification for sex and performance status , patients were r and omly assigned to receive chemotherapy with methotrexate , doxorubicin ( Adriamycin ; Adria Laboratories , Columbus , OH ) , cyclophosphamide , and lomustine ( CCNU ) ( MACC ) , or MACC plus warfarin ( MACC + W ) , or mitomycin , etoposide , cisplatin , and hexamethylmelamine alternating with MACC ( MEPH/MACC ) . Warfarin was given continuously to maintain a prothrombin time of one and one half to twice the control values . A total of 328 patients were enrolled , and 294 were evaluable . There was a statistically significant advantage in objective response rates ( complete [ CR ] and partial responses [ PR ] , respectively ) for MACC + W ( 17 % and 50 % ) as compared with MACC alone ( 8 % and 43 % ) or MEPH/MACC ( 10 % and 38 % ) ( P = .012 ) . Both failure-free survival ( P = .054 Wilcoxon test ) and overall survival ( P = .098 Wilcoxon test ) were higher on MACC + W ( median , 6.6 months and 9.3 months , respectively ) , as compared with MACC ( 5.0 months and 7.9 months ) and MEPH/MACC ( 5.0 months and 7.9 months ) . Toxicity was comparable among the three arms , except for increased hemorrhagic events on MACC + W , which were life-threatening in four patients ( 4 % ) , and lethal in two others ( 2 % ) . These data support the role of warfarin in the treatment of SCCL , but do not establish its mechanism of action . Warfarin deserves further studies in SCCL , particularly in patients with limited disease VA Cooperative Study # 75 was established to test in a controlled , r and omized trial the hypothesis that warfarin anticoagulation would favorably affect the course of certain types of malignancy . No differences in survival were observed between warfarin‐treated and control groups for advanced non‐small cell lung , colorectal , head and neck and prostate cancers . However , warfarin therapy was associated with a significant prolongation in the time to first evidence of disease progression ( P = 0.016 ) and a significant improvement in survival ( P = 0.018 ) for patients with small cell carcinoma of the lung , including the subgroup of patients with disseminated disease at the time of r and omization ( P = 0.013 ) . A trend toward improved survival with warfarin treatment was observed for the few patients admitted to this study with non‐small cell lung cancer who had minimal disease at r and omization . These results suggest that warfarin , as a single anticoagulant agent , may favorably modify the course of some , but not all , types of human malignancy , among which is small cell carcinoma of the lung . Further trials of warfarin may be indicated in patients with limited disease who have cell types that failed to respond when advanced disease was present The object of this study was to see if the addition of anticoagulants to a regimen of cytotoxic drugs would improve the prognosis in patients with small cell carcinoma of the bronchus . Twenty-four patients were r and omly allocated to receive chemotherapy or chemotherapy plus anticoagulants . The median survival in the group receiving the anticoagulants was not improved Analysis of data from a r and omised trial of adjuvant razoxane involving 603 patients with colo-rectal cancer having curative surgery is reported . The results show that razoxane was ineffective but peri-operative subcutaneous heparin treatment apparently conferred a statistically significant improvement in survival at 5 years , or equivalently a reduction in the risk of death . This beneficial effect is apparent in both razoxane treated and control patients and is not explained by demonstrable differences between heparin and non-heparin treated patients in the distribution of known prognostic factors . Adjustment for these factors slightly increased the apparent magnitude of the beneficial effect . RésuméL'analyse des résultats d'une étude r and omisée sur le traitement adjuvant par Razoxane et comprenant 603 patients porteurs d'un cancer colo-rectal ayant eu une chirurgie curatrice est reportée . Les résultats montrent que le Razoxane était inefficient mais que le traitement péri-opératoire par Héparine sous cutanée montrait apparemment une amélioration statistiquement significative dans la survie à 5 ans ou de façon équivalente une réduction du risque de mort . Cet effet bénéfique est apparent dans les deux groupes de patients traités par Razoxane et contrôles et n'est pas expliqué par une différence de la distribution des facteurs pronostiques connus entre les patients héparinés ou non héparinés . L'ajustement de ces facteurs augmente légèrement l'ampleur apparente de cet effet bénéfique In this r and omized trial adjuvant cytotoxic portal vein perfusion in patients undergoing surgery for colorectal cancer without liver metastases was assessed to determine whether the incidence of meta‐chronous liver metastases could be reduced and survival thereby improved . There were 127 control patients and 117 patients who received adjuvant perfusion . A further 13 patients were excluded following r and omization because of cirrhosis in 1 , liver metastases at laparotomy in 3 and technical problems with cannulation in 9 . Dukes ' staging and degree of differentiation were similar in the two groups . There were fewer liver metastases in the perfusion patients and overall survival was improved . However , the benefit appears to be greatest in patients with Dukes ' B colon cancer This prospect ively r and omized clinical trial was carried out in four Dutch hospitals to reduce the development of metachronous liver metastases and to get a better survival in patients with colorectal malignancies after surgically radical en bloc resection of the primary tumor and the regional lymph nodes . Three hundred seventeen patients were r and omized to participate in three trial arms . One group of patients was treated by surgery alone ( control group ) ; in the other patients a catheter was placed in the dilated umbilical vein and advanced until the tip was lying in the left branch of the portal vein . Fifty percent of these patients got immediate postoperative portal infusion with 1 g 5‐fluorouracil ( 5‐FU ) and 5000 U heparin daily for 7 days ; the others received portal vein infusion with urokinase 10,000 U/hour for 24 hours only . Three hundred four patients were eligible . Overall hospital mortality was 3.6 % ( 11 patients ) and was not influenced by adjuvant treatment . After a median follow‐up of 44 months 66 patients have died with relapse and 21 as a result of other causes . The chance of developing liver metastases and other distant metastases after portal infusion with 5‐FU/heparin was one third of the chance in the control group ( P < 0.001 ) . Only an insignificant reduction of the average death rate in the 5‐FU/heparin group was found . In the urokinase group no significant effect in reducing metastases or in survival was noted . Before recommending cytotoxic portal infusion as an adjuvant treatment in patients with colorectal cancer , detailed analysis of other ongoing portal infusion studies has to be awaited and careful calculations have to be made regarding how many patients really can be saved by this treatment Colorectal liver metastases develop by malignant cells entering the portal venous circulation . A r and omized prospect i ve clinical trial was commenced in 1975 to assess the value of adjuvant umbilical vein cytotoxic perfusion ( with 5‐fluorouracil ) following colorectal resection |
1,255 | 24,777,144 | Conclusions : Catheter locking with TCLS reduced the risk of CRB and Gram-negative bacterial infection . | Background : Preliminary evidence from some studies suggests that taurolidine-citrate locks decrease catheter-related bacteremia ( CRB ) , which is a major cause of morbidity and mortality in patients using intravascular catheters .
No previous study has sought to summarize existing evidence on the use of taurolidine-citrate locks .
A systematic review and meta- analysis were undertaken to determine whether taurolidine-citrate was more effective than heparin in the prevention of CRB . | Fifty-seven patients developed an episode of catheter-related infection ( CRI ) in the bloodstream during their stay in the intensive care unit ( cases ) and were prospect ively observed to establish the attributable mortality , increase in length of stay , and excess costs . Costs were estimated by multiplying the number of excess days of stay by the reimbursement provided . The outcomes for these cases were compared with those for matched control subjects without CRI . Eight cases were excluded as no control was found . Of the 49 cases , 31 were coagulase-negative staphylococci ( CNS ) . The level of severity was similar for both groups ( APACHE II 15.5 + /- 7 . 2 versus 15.2 + /- 7.3 ) . There were no significant differences ( p > 0 . 20 ) in the mortality observed in the hospital for the cases ( 22.4 % , 95 % confidence interval [ CI ] 0.3 % to 34.9 % ) and the control subjects ( 34.7 % , 95 % CI 21.2 % to 40.1 % ) . Among the survivors , the hospital stay was increased by 19.6 d ( 95 % CI -1.1 ; 40.4 ) . This represents an added cost of 3,124 Euros per episode of CRI among the survivors . In conclusion , our cohort study failed to show a difference in attributable mortality due to CRI in intensive care unit patients . Nevertheless , these infections lead to an increase in hospital stay of approximately 20 d. Each episode of CRI represents an additional cost of more than 3,000 Euros BACKGROUND The use of indwelling central venous catheters ( CVCs ) has become commonplace in the management of children undergoing anticancer treatment . Several types of CVC are available , while information on complications observed in children is scarce . We describe the experience of two tertiary care centers in Italy that prospect ively followed up three types of CVC used at both institutions over a 30-month period . PATIENTS AND METHODS Between January 2000 and May 2002 , double-lumen ( DL ) or single-lumen ( SL ) Hickman-Broviac ( HB ) catheters , and single-lumen pressure-activated safety valve ( PASV ) catheters were used and prospect ively evaluated . Four types of possible complication were defined a priori : mechanical , thrombotic , malfunctioning and infectious . RESULTS Four hundred and eighteen CVCs ( 180 SL-HB , 162 DL-HB and 76 PASV ) were inserted in 368 children , for a total of 107 012 catheter days at risk of complication . At least one complication occurred while using 169 of the devices ( 40 % ) : 46 % of the DL-HB , 46 % of the PASV and 33 % of the SL-HB ( P=0.02 ) catheters . Subjects with hematological malignancies or non-malignant diseases had significantly more complications than those with solid tumors ( P < 0.0001 ) . Overall , 234 complications were documented : 93 infectious [ complication rate per 1000 catheter days at risk (CR)=0.87 ] , 84 malfunctioning ( CR=0.78 ) , 48 mechanical ( CR=0.45 ) and nine thrombotic ( CR=0.08 ) . SL-HB had statistically fewer infectious complications , while PASV had more mechanical complications . In a multivariate regression model , the most significant risk factors for having a CVC complication were hematological disease [ relative risk (RR)=3.0 ; 95 % confidence interval ( CI ) 1.8 - 4.8 ] and age < 6 years at CVC insertion ( RR=2.5 ; 95 % CI 1.5 - 4.1 ) . As for the type of CVC , compared with SL-HB , the DL-HB catheter had a statistically significant two-fold increased risk of any complication ( RR=2.1 ; 95 % CI 1.2 - 3.6 ) , while the PASV catheter had a borderline RR of 1.8 ( 95 % CI 1.0 - 3.6 ) . Analysis by tumor type showed a higher risk of any kind of complication in patients with solid malignancies who had received a DL-HB catheter as compared with an SL-HB catheter ( RR=7.2 ; 95 % CI 2.8 - 18.7 ) . CONCLUSIONS CVCs may cause complications in up to 40 % of patients , with type of CVC , underlying disease and patient age being the three main factors that affect the incidence of CVC-related complications . SL-HB catheters have the best performance Taurolidine has demonstrated inhibition of biofilm formation in vitro . The aim of this study was to compare the effect of catheter locking with taurolidine vs heparin in biofilm formation in central venous catheters . Forty‐eight children with cancer were r and omized to catheter locking by heparin ( n = 22 ) or taurolidine ( n = 26 ) , respectively . After removal , catheters were examined by st and ardized scanning electron microscopy to assess quantitative biofilm formation . Biofilm was present if morphologically typical structures and bacterial cells were identified . Quantitative and semi‐quantitative cultures were also performed . Biofilm was identified in 23 of 26 catheters from the taurolidine group and 21 of 22 catheters from the heparin group . A positive culture was made of six of the catheters locked with taurolidine and heparin , respectively ( p = 0.78 ) . The rate of catheter‐related bloodstream infections ( CRBSI ) was 0.1 per 1000 catheter‐days using taurolidine and 0.9 per 1000 catheter‐days using heparin ( p = 0.03 ) . This r and omized trial confirmed that the use of taurolidine as catheter‐lock compared with heparin reduced the rate of CRBSIs ; this reduction was not related to a reduction in the intraluminal biofilm formation and the rate of bacterial colonization detected by scanning electron microscopy in the two groups HYPOTHESIS Catheter-related bloodstream infection ( CRBSI ) in critically ill surgical patients with prolonged intensive care unit ( ICU ) stays is associated with a significant increase in health care re source use . DESIGN Prospect i ve cohort study . SETTING Surgical ICU at a large tertiary care center . PATIENTS Critically ill surgical patients ( N = 260 ) with projected surgical ICU length of stay greater than 3 days . INTERVENTIONS Central venous catheters were cultured for clinical suspicion of infection . MAIN OUTCOME MEASURES Increases in total hospital cost , ICU cost , hospital days , and ICU days attributable to CRBSI were estimated using multiple linear regression after adjusting for demographic factors and severity of illness ( APACHE III [ Apache Physiology and Chronic Health Evaluation III ] score ) . RESULTS The incidence of CRBSI per 1000 catheter-days was 3.6 episodes ( 95 % confidence interval [ CI ] , 2.1 - 5.8 episodes ) . Microbiologic isolates were Gram-positive bacteria in 75 % , Gram-negative bacteria in 20 % , and yeast in 5 % . After adjusting for demographic factors and severity of disease , CRBSI was associated with an increase of $ 56 167 ( 95 % CI , $ 11 523-$165 735 ; P = .001 ) ( in 1998 dollars ) in total hospital cost , an increase of $ 71 443 ( 95 % CI , $ 11 960-$195 628 ; P<.001 ) in ICU cost , a 22-day increase in hospital length of stay , and a 20-day increase in ICU length of stay . CONCLUSIONS For critically ill surgical patients , CRBSI is associated with a profound increase in re source use . Prevention , early diagnosis , and intervention for CRBSI might result in cost savings in this high-risk population Background Taurolidin/Citrate ( TauroLock ™ ) , a lock solution with broad spectrum antimicrobial activity , may prevent bloodstream infection ( BSI ) due to coagulase-negative staphylococci ( CoNS or ' MRSE ' in case of methicillin-resistant isolates ) in pediatric cancer patients with a long term central venous access device ( CVAD , Port- or/Broviac-/Hickman-catheter type ) . Methods In a single center prospect i ve 48-months cohort study we compared all patients receiving anticancer chemotherapy from April 2003 to March 2005 ( group 1 , heparin lock with 200 IU/ml sterile normal saline 0.9 % ; Canusal ® Wockhardt UK Ltd , Wrexham , Wales ) and all patients from April 2005 to March 2007 ( group 2 ; taurolidine 1.35%/Sodium Citrate 4 % ; TauroLock ™ , Tauropharm , Waldbüttelbrunn , Germany ) . Results In group 1 ( heparin ) , 90 patients had 98 CVAD in use during the surveillance period . 14 of 30 ( 47 % ) BSI were ' primary Gram positive BSI due to CoNS ( n = 4 ) or MRSE ( n = 10 ) ' [ incidence density ( ID ) ; 2.30 per 1000 inpatient CVAD-utilization days].In group 2 ( TauroLock ™ ) , 89 patients had 95 CVAD in use during the surveillance period . 3 of 25 ( 12 % ) BSI were caused by CoNS . ( ID , 0.45 ) . The difference in the ID between the two groups was statistically significant ( P = 0.004 ) . Conclusion The use of Taurolidin/Citrate ( TauroLock ™ ) significantly reduced the number and incidence density of primary catheter-associated BSI due to CoNS and MRSE in pediatric cancer patients Abstract Objective . To prevent catheter occlusion , intermittently used central venous catheters are frequently sealed with vitamin C solution or heparin solution between use . The present study was design ed to test the effectiveness of this approach and to compare the efficiency of sealing solutions . Design and setting . Prospect i ve r and omized study performed on a 9-bed medical ICU and on medical wards of an academic tertiary care center . Participants . Ninety-nine central venous line placements were prospect ively included in the study and r and omized into three treatment groups : sodium chloride 0.9 % , vitamin C ( 200 mg/ml ) and heparin ( 5000 IU/ml ) sealing solutions . Interventions and measurements . Catheters were filled with the respective sealing solution and patency was tested once every 2 days using a st and ardized routine . Catheter patency was compared among the three groups using Kaplan-Meier statistics and log-rank testing . Results . There was a significant difference in catheter patency between the three groups ( p<0.03 , log-rank test ) . A comparison of catheter survival between the catheters filled with heparin and those filled with sodium chloride , but not between those filled with vitamin C solution and with sodium chloride solution , exhibited significant differences in catheter patency ( p<0.04 , log-rank test ) . Conclusions . Local anticoagulation of intermittently used central venous catheters prolongs catheter patency . High-dose ( 5000 IU/ml ) heparin solution is a useful anticoagulant for this purpose , while vitamin C solution does not prolong catheter patency BACKGROUND Bacteremia is a major cause of morbidity in patients using intravascular catheters . Interdialytic locking with antibiotics decreases the incidence of bacteremia , but risks antibiotic resistance . Taurolidine is a nontoxic broad-spectrum antimicrobial agent that has not been associated with resistance . Preliminary evidence suggests that taurolidine-citrate locks decrease bacteremia , but cause flow problems in established catheters . STUDY DESIGN Double-blind r and omized controlled trial . INTERVENTION Interdialytic locking with taurolidine and citrate ( 1.35 % taurolidine and 4 % citrate ) compared with heparin ( 5,000 U/mL ) started at catheter insertion . SETTING & PARTICIPANTS 110 adult hemodialysis patients with tunneled cuffed intravascular catheters inserted at 3 centers in Northwest Engl and . OUTCOMES & MEASUREMENTS Primary end points were time to first bacteremia episode from any cause and time to first use of thrombolytic therapy . RESULTS There were 11 bacteremic episodes in the taurolidine-citrate group and 23 in the heparin group ( 1.4 and 2.4 episodes/1,000 patient-days , respectively ; P = 0.1 ) . There was no significant benefit of taurolidine-citrate versus heparin for time to first bacteremia ( hazard ratio , 0.66 ; 95 % CI , 0.2 - 1.6 : P = 0.4 ) . Taurolidine-citrate was associated with fewer infections caused by Gram-negative organisms than heparin ( 0.2 vs 1.1 infections/1,000 patient-days ; P = 0.02 ) ; however , there was no difference for Gram-positive organisms ( 1.1 vs 1.2 infections/1,000 patient-days ; P = 0.8 ) . There was a greater need for thrombolytic therapy in the taurolidine-citrate versus heparin group ( hazard ratio , 2.5 ; 95 % CI , 1.3 - 5.2 ; P = 0.008 ) . LIMITATIONS Small sample size . The study included bacteremia from all causes and was not specific for catheter-related bacteremia . CONCLUSIONS Taurolidine-citrate use did not decrease all-cause bacteremia and was associated with a greater need for thrombolytic treatment . There was a decrease in infections caused by Gram-negative organisms and a trend to a lower frequency of bacteremia , which warrants further study Seventy-four subclavian hemodialysis catheters inserted into 53 patients were studied prospect ively . Sixteen of 64 assessable catheterization periods were complicated by clinical ly documented catheter-related sepsis , and 13 had an associated bacteremia . One patient died from catheter-related sepsis , and in two others , sepsis contributed to death . Staphylococci accounted for 11 bacteremias . Semiquantitative culture of the catheters indicated that 28 were significantly colonized . Comparison of these isolates with skin cultures from the insertion site suggested that the origin of the colonizing organisms was the skin ( 10 cases ) , intralumenal contamination ( 16 cases ) , or both routes ( 2 cases ) . Comparison of cultures taken during catheter insertion with those at removal rarely suggested that organisms introduced at insertion caused subsequent colonization . This study has demonstrated that infectious complications from using subclavian hemodialysis catheters exceed reported rates for all other modes of vascular access used for hemodialysis , as well as other indications for central venous catheterization Catheter-related bacteremia ( CRB ) is one of the various complications related to hemodialysis ( HD ) . As a result of this high rate of infection , the antibiotic lock technique ( ALT ) has been recommended to prevent CRB . However , adverse effects of ALT such as increased emergence of strains resistant to antibiotics and increased mechanical dysfunction catheter were poorly evaluated . We prospect ively evaluated the efficacy of catheter-restricted filling using an antibiotic lock solution in preventing CRB . A total of 233 HD patients requiring 325 new tunneled catheters while waiting for placement and maturation of an arteriovenous fistula or graft were enrolled in this study . Patients with a tunneled catheter were assigned to receive either an antibiotic – heparin lock solution ( antibiotic group : cefazolin 10 mg/ml , gentamicin 5 mg/ml , heparin 1,000 U/ml ) or a heparin lock solution ( no-antibiotic group : heparin 1,000 U/ml ) as a catheter lock solution during the interdialytic period . The present study aim ed to assess the efficacy of ALT using cefazolin and gentamicin in reducing CRB in patients undergoing HD with tunneled central catheter and to identify its adverse effects . CRB developed in 32.4 % of patients in the no-antibiotic group and in 13.1 % of patients in the antibiotic group . CRB rates per 1,000 catheter-days were 0.57 in the antibiotic group versus 1.74 in the no-antibiotic group ( p < 0.0001 ) . Kaplan – Meier analysis also showed that mean CRB-free catheter survival was significantly higher in the antibiotic group than in the no-antibiotic group ( log-rank statistic 17.62 , p < 0.0001 ) . There was statistically significant difference between the two groups in causative organisms of CRB , with predominance of negative culture in both groups , but this prevalence was higher in ALT group ( 57.9 vs 90.1 % , p < 0.0001 ) , and the two groups also were different in prevalence of gram-positive bacteria as causing organisms ( ALT group 21.05 vs = 0 % in control group , p < 0.0001 ) . There was no statistically significant difference between the two groups in drug-resistant germs . There were statistically significant differences between the two groups in the catheter removal causes , with higher rate of infectious cause in control group ( 12.32 vs 2.22 % , p < 0.0001 ) and mechanical cause in ALT group ( 28.26 vs 37.78 % , p < 0.0001 ) . The results suggest that ALT may be a beneficial means of reducing the CRB rate in HD patients with tunneled catheter , without association between ALT and emergence of strains resistant . However , mechanical complications were more prevalent in antibiotic group . Further studies are required to determine the optimal drug regimen , concentrations for ALT , and its adverse effects Background : Use of uncuffed catheters ( UCs ) in hemodialysis patients is common practice . An antibiotic lock has been recommended to prevent catheter-related bacteremia ( CRB ) , although insufficient data are available about the appropriate antimicrobial agent and dose with prolonged use of UCs . Methods : This open-label r and omized study was conducted to compare gentamicin/heparin ( group A ) and taurolidine/citrate ( group B ) , as catheter-lock solutions , in 119 chronic hemodialysis patients in whom a total of 150 UCs were placed . A well-matched historical control group ( heparin ) included 67 UCs in 58 patients ( group C ) . Results : CRB episodes developed in 6 and 8 patients in groups A and B , respectively , significantly fewer than in group C ( 20 patients ) . Cumulative CRB-free catheter survival at 90 days was 82 % for A and 78 % for B , which is significantly higher than the 26 % for C. Similar Gram-positive infection rates were found in all groups . The Gram-negative infection rate was significantly lower in B compared to C. No significant differences in thrombosis rates were observed between the groups . Conclusions : Gentamicin/heparin and taurolidine/citrate , used for locking UC , were similarly effective at preventing CRB and catheter thrombosis for up to 3 months , until a functional permanent vascular access became available . Both antimicrobial lock solutions were superior to heparin in CRB prevention with similar thrombosis rates OBJECTIVE To assess the benefit gained from administration of the antiendotoxic drug , taurolidine , on outcome in critically ill patients with sepsis syndrome . DESIGN A prospect i ve , r and omized , double-blind trial . SETTING The general intensive therapy unit in a university teaching hospital . PATIENTS One hundred patients admitted with sepsis syndrome over a 2-yr period . INTERVENTIONS Patients were r and omized to receive the amino-acid derivative , taurolidine , or an identically presented placebo . MEASUREMENTS AND MAIN RESULTS Acute Physiology and Chronic Health Evaluation II ( APACHE II ) , sepsis , and organ failure scores were measured daily . Blood for culture and endotoxin assay ( using the limulus amoebocyte lysate assay ) was sample d every 12 hrs for up to 5 days . Hemodynamic variables were recorded every 4 hrs . Forty-nine patients received taurolidine and 51 patients received placebo . There was no difference in APACHE II score , Sepsis Score , or presence of infections between the groups . The frequency of Gram-negative bacteremia was low at 12 % . There was no difference in endotoxin activity , clinical or bacteriologic outcome , resolution of organ failure , or mortality rate between groups . Predicted risk of death for patients receiving taurolidine was 45 % , and the actual mortality rate was 44 % . In the group that received placebo , the predicted mortality rate was 38 % and the actual mortality rate was 39 % . CONCLUSION Taurolidine had no beneficial therapeutic effect on the outcome of patients admitted to the intensive therapy unit with sepsis syndrome , using clinical , bacteriologic outcomes , progression of endotoxemia , resolution of organ failure , and 28-day mortality rate as end points BACKGROUND The use of haemodialysis catheters is complicated by catheter-related sepsis . Intraluminal colonization of the catheter with bacteria is important in the pathogenesis of catheter-related sepsis . The use of a catheter lock solution containing the antimicrobial taurolidine might prevent bacterial colonization , thereby reducing the incidence of catheter-related sepsis . METHODS In a r and omized prospect i ve trial , patients receiving a dialysis catheter were included and catheters were locked with either heparin or a citrate-taurolidine-containing solution . Blood cultures drawn from the catheter lumen were routinely taken every 2 weeks and at time of removal of the catheter to detect bacterial colonization . Catheter-related sepsis and exit-site infections were registered for both groups . RESULTS A total of 76 catheters were inserted in 58 patients . The incidence of catheter colonization progressed slowly over time with no differences between dialysis catheters filled with heparin or citrate-taurolidine-containing solution . The number of exit-site infections was also similar between both groups . In the heparin group , four cases of catheter-related sepsis occurred as opposed to no sepsis episodes in the patients with catheters locked with the citrate-taurolidine-containing solution ( P<0.5 ) . No side effects with the use of citrate-taurolidine catheter lock solution were noted . CONCLUSIONS This study shows that catheter filling with a solution containing the antimicrobial taurolidine may significantly reduce the incidence of catheter-related sepsis . Taurolidine appears to be effective and safe and does not carry the risk for side effects that have been reported for other antimicrobial lock solutions containing gentamicin or high concentrations of citrate BACKGROUND Intravenous catheters for haemodialysis increase the risk of sepsis . This study investigates the use of a taurolidine/citrate catheter-locking agent for patients receiving hospital-based haemodialysis , auditing the number and cost of infections before and after its introduction . METHODS The incidence and cost of treatment of catheter sepsis occurring in all patients receiving haemodialysis via a line were investigated over 6-month periods before and after introducing the taurolidine/citrate line-locking agent . RESULTS A reduction of 4.62 infections per 1000 catheter days , or 88.5 % , was shown after the introduction of the new line-locking agent . The total costs of line infections in the first 6 months were 52,500 euros , ( 41,000 pounds ) ; after the introduction of the taurolidine/citrate locks , these reduced to 33,300 euros , ( 26 , 000 pounds ) , a reduction of 19,200 euros ( 15,000 pounds ) . CONCLUSIONS The use of a taurolidine/citrate haemodialysis catheter-locking agent in our haemodialysis population has significantly reduced the line sepsis rate , with a positive impact on morbidity , mortality and cost BACKGROUND A catheter lock solution containing 1.35 % taurolidine and 4 % citrate could potentially disrupt bacterial surface adherence and consecutive biofilm production due to the anti-adherence properties of taurolidine and the anticlotting and chelator activities of both compounds . AIM To compare the impact on microbial catheter colonization and infectious complications of heparin and taurolidine citrate as central venous catheter ( CVC ) lock solutions in paediatric patients with haematological malignancies . METHODS Seventy-one patients aged 1.4 - 18 years were r and omized to two treatment groups using either heparin ( N = 36 ) or taurolidine citrate ( N = 35 ) . Infectious complications and clinical side-effects were prospect ively monitored and microbial colonization of catheters was assessed at the time of removal . FINDINGS There were two bloodstream infections in the taurolidine citrate group versus nine in the heparin group ( 0.3 vs 1.3 infections per 1000 catheter-days ; P = 0.03 ) . Fever of unknown origin and catheter occlusions were observed with a similar frequency in both groups . Microbial colonization was found in 25.4 % catheters . The time of no-lock use , but not the type of lock solution or time of observation , was a significant predictor of catheter colonization ( P = 0.004 ) . Colonization was not observed in CVCs used immediately with taurolidine citrate lock . Seven patients in the taurolidine citrate group ( 20 % ) experienced side-effects ( nausea , vomiting , abnormal taste sensations ) . CONCLUSION The use of taurolidine citrate lock solution was associated with a significant reduction in bloodstream infection in immunocompromised paediatric patients . Taurolidine citrate may prevent colonization of CVCs if used from the time of insertion , but not after a period of no-lock catheter use |
1,256 | 21,984,641 | Results indicated beneficial effects of positive , instructional , and motivational self-talk for performance .
First , negative self-talk did not impede performance .
Second , there was inconsistent evidence for the differential effects of instructional and motivational self-talk based on task characteristics .
Results from the mediation-based analysis indicate that cognitive and behavioral factors had the most consistent relationships with self-talk . | This article presents a systematic review of the literature examining the relationship between self-talk and performance . | The current study examined the effects of performance enhancement techniques ( PET 's ) on motor skill performance . Specifically , one hundred fifty college student volunteers ( Men = 41 ; 27.3 % and Women = 109 ; 72.6 % ) were r and omly assigned to one of the nine conditions ( Cond ) : Cond 1 and 2 , simultaneous , externally verbalized self-talk or imagery ( e.g. , participants were instructed to say " aim , back , birdie " or engaged in imagery out loud while putting ) ; Cond 3 and 4 , delayed externally verbalized self-talk or imagery ( e.g. , participants were instructed to say " aim , back , birdie " or engaged in imagery out loud before putting ) ; Cond 5 and 6 , simultaneous , internally verbalized self-talk or imagery ( e.g. , participants were instructed to say " aim , back , birdie " or engaged in imagery silently to oneself while putting ) ; Cond 7 and 8 , delayed internally verbalized ( e.g. , participant were instructed to say " aim , back , birdie " or engaged in imagery silently to oneself before putting ) ; and Cond 9 , no instruction control group . All participants were asked to perform a golf-putting task . Results indicated that participants who implemented several ( PET 's ) increased their putting accuracy across overall difference score evaluations F ( 8 , 141 ) = 4.01 , p < 0.05 when compared to a no instruction control condition . Follow-up analyses indicated that participants who reportedly engaged in ten hours or less of athletic activities per week preferred self-talk strategies F ( 2 , 119 ) = 4.38 , p < 0.05 whereas participants who endorsed ten hours or more of athletic activity per week preferred imagery strategies F ( 2 , 25 ) = 5.27 , p < 0.05 . Key PointsMental imagery and self-talk strategies are implemented by athletes in order to regulate arousal , reduce maladaptive behaviors , reconstruct negative thoughts , and to increase one 's concentration and focus . Results of the current study suggest that participants who engaged in several performance enhancement techniques exhibited enhanced performance on a golf putting task when compared to participants in a control condition . Participants who endorsed limited athletic familiarity and activity ( e.g. , ten hours or less ) preferred self-talk practice whereas participants who endorsed higher ratings scores of athletic familiarity and activity ( e.g. , ten hours or more ) preferred imagery strategies . The results of this study demonstrate the flexibility of Performance Enhancement Techniques ( e.g. , imagery v. self-talk , internal v. external , simultaneous v. delayed ) and how they can be implemented to help an athlete reach his or her full potential In this study , we examined ( 1 ) the relationship between self-talk and affect and ( 2 ) the nature of motivating self-talk . Ninety high-school athletes completed the Affect Grid and the Self-Talk Grid before practice and competition . Significant positive second-order partial correlations of low to moderate strength offered support for a relationship between self-talk and affect . In addition , significant positive second-order partial correlations of moderate strength were found for a relationship between negative-positive self-talk and demotivating-motivating self-talk . An examination of scatter plots indicated that some athletes rated their self-talk as negative as well as being motivational . These findings lend support to the suggestion that negative self-talk may motivate some athletes The effects of instructions to use three different types of thought patterns on the practice performance of superior age-group swimmers were assessed . Two different swimming tasks , two 40 degrees m effort swims and a set of eight 100 m repeats , were used . A balanced design allowed the comparison of the totals of treatment and control ( normal thinking ) conditions . All Ss improved in at least two of the three conditions . All manipulations were significant at the 0.05 level . Group averages indicated that task-relevant content was the most effective condition , followed by mood works , and positive thinking . The importance of using thought content instructions for improving performance was supported by this investigation Abstract This study examined the effects of a cognitive-hypnotic-imagery approach ( CHI ) , cognitive restructuring ( CR ) , and hypnosis only ( HO ) treatments on neuro-muscular performance , muscular growth , reduction of anxiety , and enhancement of self-concept . Thirty-two volunteer male weightlifters served as subjects for the study . Eight subjects were r and omly assigned to each of four treatment conditions conducted over a four-week period . A 4 × 3 factorial design utilizing CANOVA and MANOVA programs was employed . The CHI group showed statistically significant treatment effects over the other groups on all six dependent variables from pretest to post Test I. From post Test I to post Test II , a time period in which no treatment was conducted , self-concept and muscular growth measures for CHI showed significance . The CHI group was statistically superior to all other conditions , ( CR , HO , control ) , which did not significantly differ from each other . Neuro-muscular performance ( supine barbell press mean increase o |
1,257 | 21,203,822 | Conclusion Published literature provides little evidence to support a major role of vitamin D in preventing prostate cancer or its progression | Objective We systematic ally review ed and meta-analyzed literature examining associations of vitamin D ( dietary intake , circulating 25-hydroxy-vitamin-D ( 25(OH)D ) , and 1,25-dihydroxy-vitamin-D ( 1,25(OH)2D ) concentrations ) with prostate cancer . | Objective Multiple studies have shown clear evidence of vitamin D ’s anti-tumor effects on prostate cancer cells in laboratory experiments , but the evidence has not been consistent in humans . We sought to examine the association between vitamin D and prostate cancer risk in a cohort of older men . Methods We conducted a prospect i ve case-cohort study nested within the multicenter Osteoporotic Fractures in Men ( MrOS ) study . Baseline serum 25-OH vitamin D was measured in a r and omly selected sub-cohort of 1,433 men ≥65 years old without a history of prostate cancer and from all participants with an incident diagnosis of prostate cancer ( n = 297 ) . Cox proportional hazards models were used to evaluate the associations between quartiles of total 25-OH vitamin D and incident prostate cancer , as well as Gleason score . Results In comparison with the lowest quartile of 25-OH vitamin D , the hazard ratio for the highest quartile of 25-OH vitamin D was 1.22 ( CI 0.50–1.72 , p = 0.25 ) , no trend across quartiles ( p = 0.94 ) or association with Gleason score was observed . Adjustment for covariates did not alter the results . Conclusions In this prospect i ve cohort of older men , we found no association between serum 25-OH vitamin D levels and subsequent risk of prostate cancer 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 This population -based , case-control study in King County , Washington examined associations of energy , fat , vitamin D , and calcium with risk of prostate cancer in 605 incident cases ( ages 40 - 64 years ) identified from the Seattle-Puget Sound Surveillance Epidemiology and End Results registry and 592 controls recruited from the same underlying population using r and om-digit telephone sampling . Self-administered food frequency question naires were used to assess diet over the 3 - 5-year period before diagnosis or interview date . Total energy was associated with increased risk for both local and regional/distant stage disease . The adjusted odds ratios [ 95 % confidence intervals ( CIs ) ] contrasting highest to lowest quintile of energy intake were 2.15 ( 95 % CI , 1.35 - 3.43 ) for local and 1.96 ( 95 % CI , 1.08 - 3.56 ) for regional/distant disease . Fat was associated with regional/distant disease only . Adjusted odds ratios comparing the highest to lowest quintiles of percentage energy from total , saturated , and monounsaturated fats were 2.01 ( 1.03 - 3.92 ) , 1.82 ( 0.93 - 3.56 ) , and 2.00 ( 1.03 - 3.87 ) , respectively . For calcium , adjusted odds ratios contrasting the highest to lowest quartiles were 1.07 ( 0.63 - 1.84 ) for local and 2.12 ( 1.02 - 4.38 ) for regional/distant disease . There were no associations of vitamin D , total polyunsaturated fatty acids , or the highly unsaturated , long-chain eicosapentainoic and docosahexaenoic fatty acids with prostate cancer risk . These results suggest that high energy intake is a risk factor for both localized and nonlocalized prostate cancer , whereas dietary fat and calcium increase the risk of regional/distant disease only . These results are consistent with general dietary guidelines to moderate consumption of total energy and fat , and they motivate further research to consider the potential benefits and risks of high calcium intake A major problem in review ing the published results of different epidemiologic studies of the relation between a quantitative variable and the risk of disease is that the results are presented in many different ways . The purpose of this paper is to exemplify methods by which results expressed either as risks ( or rates ) according to quantlle groups of the quantitative variable or as results derived from a logistic regression analysis can be reexpressed in a uniform manner , as a mean difference in the quantitative variable between the cases of disease and the other subjects in the study . An important assumption of the methods is that the quantitative variable has an approximately normal distribution , and a way of investigating the appropriateness of this assumption is given . The methods can be applied to both prospect i ve and case-control studies and are exemplified by a number of studies of serum albumin concentrations and mortality . In some applications , these methods can be used as a precursor to formal meta- analysis , for example , when differential control of potential confounding factors is not a problem . At the least , the methods can be useful either in quantitatively review ing published studies before undertaking new research or in putting the results of a new study into the context of previously published ones BACKGROUND Dairy intake may increase prostate cancer risk , but whether this is due to calcium 's suppression of circulating vitamin D remains unclear . Findings on calcium and vitamin D intake and prostate cancer are inconsistent . OBJECTIVE We examined the association of dairy , calcium , and vitamin D intake with prostate cancer . DESIGN In a prospect i ve study of 3612 men followed from 1982 - 1984 to 1992 for the first National Health and Nutrition Examination Epidemiologic Follow-up Study , 131 prostate cancer cases were identified . Dietary intake was estimated from question naires completed in 1982 - 1984 . Relative risk ( RR ) and 95 % CIs were estimated by using Cox proportional hazards models adjusted for age , race , and other covariates . RESULTS Compared with men in the lowest tertile for dairy food intake , men in the highest tertile had a relative risk ( RR ) of 2.2 ( 95 % CI : 1.2 , 3.9 ; trend P = 0.05 ) . Low-fat milk was associated with increased risk ( RR = 1.5 ; 95 % CI : 1.1 , 2.2 ; third compared with first tertile ; trend P = 0.02 ) , but whole milk was not ( RR = 0.8 ; 95 % CI : 0.5 , 1.3 ; third compared with first tertile ; trend P = 0.35 ) . Dietary calcium was also strongly associated with increased risk ( RR = 2.2 ; 95 % CI : 1.4 , 3.5 ; third compared with first tertile ; trend P = 0.001 ) . After adjustment for calcium intake , neither vitamin D nor phosphorus was clearly associated with risk . CONCLUSIONS Dairy consumption may increase prostate cancer risk through a calcium-related pathway . Calcium and low-fat milk have been promoted to reduce risk of osteoporosis and colon cancer . Therefore , the mechanisms by which dairy and calcium might increase prostate cancer risk should be clarified and confirmed Abstract Objective : The hormone 1,25-dihydroxyvitamin D ( 1,25(OH)2D ) promotes prostate epithelial cell differentiation in vitro and thus , several groups have hypothesized that men who systemically have lower levels of 1,25(OH)2D may be at increased risk for prostate cancer . To address this hypothesis , we evaluated the association of circulating concentrations of 1,25(OH)2D and its precursor 25-hydroxyvitamin D ( 25(OH)D ) with subsequent risk of prostate cancer . Methods : Prostate cancer cases were 460 men in the Health Professionals Follow-up Study who were diagnosed through 1998 after providing a blood specimen in 1993/95 . 90.2 % of the cases were organ confined or had minimal extraprostatic extension . An equal number of controls who had had a screening PSA test after blood draw were individually matched to cases on age , history of a PSA test before blood draw , and time of day , season , and year of blood draw . Plasma 1,25(OH)2D and 25(OH)D concentrations were determined by radio-immunosorbant assay blindly to case – control status . Odds ratios ( OR ) of prostate cancer and 95 % confidence intervals ( CI ) were estimated from conditional logistic regression models mutually adjusting for quartiles of 1,25(OH)2D and 25(OH)D concentrations and for suspected prostate cancer risk factors . Quartile cutpoints were determined separately by season of blood draw using the distributions among controls . Results : Mean concentrations of 1,25(OH)2D and 25(OH)D were slightly , but not statistically significantly ( p= 0.06 and 0.20 , respectively ) , higher in cases ( 34.3 ± 7.1 pg/ml and 24.6 ± 7.7 ng/ml , respectively ) than in controls ( 33.5 ± 7.1 pg/ml and 23.9 ± 8.2 ng/ml , respectively ) . The OR of prostate cancer comparing men in the top to bottom quartile of 1,25(OH)2D was 1.25 ( 95 % CI : 0.82–1.90 , p-trend = 0.16 ) . For 25(OH)D the OR of prostate cancer comparing the top and bottom quartiles was 1.19 ( 95 % CI : 0.79–1.79 , p-trend = 0.59 ) . These findings did not vary by level of the other metabolite , age at diagnosis , family history of prostate cancer , or factors that are thought to influence 25(OH)D levels . Conclusion : In this prospect i ve study , we did not observe an inverse association between plasma concentrations of 1,25(OH)2D or 25(OH)D and incident prostate cancer , although we can not rule out potential effects at later stages of the disease Intake of calcium and /or dairy products has been associated with increased risk of prostate cancer in some epidemiological studies . One potential biological mechanism is that high calcium intake down-regulates 1,25 dihydroxy vitamin D(3 ) , which may increase cell proliferation in the prostate . We examined the association between calcium , dairy intake , and prostate cancer incidence in the Cancer Prevention Study II Nutrition Cohort , a prospect i ve cohort of elderly United States adults . Participants in the study completed a detailed question naire on diet , medical history , and lifestyle at enrollment in 1992 - 1993 . After excluding men with a history of cancer or incomplete dietary information , 65,321 men remained for analysis . During follow-up through August 31 , 1999 , we documented 3811 cases of incident prostate cancer . Multivariate-adjusted rate ratios ( RRs ) were calculated using Cox proportional hazards models . Total calcium intake ( from diet and supplements ) was associated with modestly increased risk of prostate cancer [ RR = 1.2 , 95 % confidence interval ( CI ) = 1.0 - 1.6 for > or=2000 versus < 700 mg/day , P trend = 0.02 ) . High dietary calcium intake ( > or=2000 versus < 700 mg/day ) was also associated with increased risk of prostate cancer ( RR = 1.6 , 95 % CI = 1.1 - 2.3 , P trend = 0.10 ) , although moderate levels of dietary calcium were not associated with increased risk . Dairy intake was not associated with prostate cancer risk . The association between prostate cancer and total calcium intake was strongest for men who reported not having prostate-specific antigen testing before 1992 ( RR = 1.5 , 95 % CI = 1.1 - 2.0 , P trend < 0.01 for > or= 2000 mg/day of total calcium ; RR = 2.1 , 95 % CI = 1.3 - 3.4 > or=2000 mg/day of dietary calcium , P trend = 0.04 ) . Our results support the hypothesis that very high calcium intake , above the recommended intake for men , may modestly increase risk of prostate cancer PURPOSE Substantial experimental and epidemiological data indicate that 1,25-dihydroxyvitamin D3 ( calcitriol ) has potent antiproliferative effects on human prostate cancer cells . We performed an open label , nonr and omized pilot trial to determine whether calcitriol therapy is safe and efficacious for early recurrent prostate cancer . Our hypothesis was that calcitriol therapy slows the rate of rise of prostate specific antigen ( PSA ) compared with the pretreatment rate . MATERIAL S AND METHODS After primary treatment with radiation or surgery recurrence was indicated by rising serum PSA levels documented on at least 3 occasions . Seven subjects completed 6 to 15 months of calcitriol therapy , starting with 0.5 microg . calcitriol daily and slowly increasing to a maximum dose of 2.5 microg . daily depending on individual calciuric and calcemic responses . Each subject served as his own control , comparing the rate of PSA rise before and after calcitriol treatment . RESULTS As determined by multiple regression analysis , the rate of PSA rise during versus before calcitriol therapy significantly decreased in 6 of 7 patients , while in the remaining man a deceleration in the rate of PSA rise did not reach statistical significance . Overall the decreased rate of PSA rise was statistically significant ( p = 0.02 Wilcoxon signed rank test ) . Dose dependent hypercalciuria limited the maximal calcitriol therapy given ( range 1.5 to 2.5 microg . daily ) . CONCLUSIONS This pilot study provides preliminary evidence that calcitriol effectively slows the rate of PSA rise in select cases , although dose dependent calciuric side effects limit its clinical usefulness . The development of calcitriol analogues with decreased calcemic side effects is promising , since such analogues may be even more effective for treating prostate cancer Background : In some studies , high calcium intake has been associated with an increased risk of prostate cancer , but no r and omized studies have investigated this issue . Methods : We r and omly assigned 672 men to receive either 3 g of calcium carbonate ( 1,200 mg of calcium ) , or placebo , daily for 4 years in a colorectal adenoma chemoprevention trial . Participants were followed for up to 12 years and asked periodically to report new cancer diagnoses . Subject reports were verified by medical record review . Serum sample s , collected at r and omization and after 4 years , were analyzed for 1,25-(OH)2 vitamin D , 25-(OH ) vitamin D , and prostate-specific antigen ( PSA ) . We used life table and Cox proportional hazard models to compute rate ratios for prostate cancer incidence and generalized linear models to assess the relative risk of increases in PSA levels . Results : After a mean follow-up of 10.3 years , there were 33 prostate cancer cases in the calcium-treated group and 37 in the placebo-treated group [ unadjusted rate ratio , 0.83 ; 95 % confidence interval ( 95 % CI ) , 0.52 - 1.32 ] . Most cases were not advanced ; the mean Gleason 's score was 6.2 . During the first 6 years ( until 2 years post-treatment ) , there were significantly fewer cases in the calcium group ( unadjusted rate ratio , 0.52 ; 95 % CI , 0.28 - 0.98 ) . The calcium risk ratio for conversion to PSA > 4.0 ng/mL was 0.63 ( 95 % CI , 0.33 - 1.21 ) . Baseline dietary calcium intake , plasma 1,25-(OH)2 vitamin D and 25-(OH ) vitamin D levels were not material ly associated with risk . Conclusion : In this r and omized controlled clinical trial , there was no increase in prostate cancer risk associated with calcium supplementation and some suggestion of a protective effect BACKGROUND Epidemiological studies have yielded inconsistent associations between vitamin D status and prostate cancer risk , and few studies have evaluated whether the associations vary by disease aggressiveness . We investigated the association between vitamin D status , as determined by serum 25-hydroxyvitamin D [ 25(OH)D ] level , and risk of prostate cancer in a case-control study nested within the Prostate , Lung , Colorectal , and Ovarian ( PLCO ) Cancer Screening Trial . METHODS The study included 749 case patients with incident prostate cancer who were diagnosed 1 - 8 years after blood draw and 781 control subjects who were frequency matched by age at cohort entry , time since initial screening , and calendar year of cohort entry . All study participants were selected from the trial screening arm ( which includes annual st and ardized prostate cancer screening ) . Conditional logistic regression was used to estimate adjusted odds ratios ( ORs ) with 95 % confidence intervals ( CIs ) by quintile of season-st and ardized serum 25(OH)D concentration . Statistical tests were two-sided . RESULTS No statistically significant trend in overall prostate cancer risk was observed with increasing season-st and ardized serum 25(OH)D level . However , serum 25(OH)D concentrations greater than the lowest quintile ( Q1 ) were associated with increased risk of aggressive ( Gleason sum > or = 7 or clinical stage III or IV ) disease ( in a model adjusting for matching factors , study center , and history of diabetes , ORs for Q2 vs Q1 = 1.20 , 95 % CI = 0.80 to 1.81 , for Q3 vs Q1 = 1.96 , 95 % CI = 1.34 to 2.87 , for Q4 vs Q1 = 1.61 , 95 % CI = 1.09 to 2.38 , and for Q5 vs Q1 = 1.37 , 95 % CI = 0.92 to 2.05 ; P(trend ) = .05 ) . The rates of aggressive prostate cancer for increasing quintiles of serum 25(OH)D were 406 , 479 , 780 , 633 , and 544 per 100 000 person-years . In exploratory analyses , these associations with aggressive disease were consistent across subgroups defined by age , family history of prostate cancer , diabetes , body mass index , vigorous physical activity , calcium intake , study center , season of blood collection , and assay batch . CONCLUSION The findings of this large prospect i ve study do not support the hypothesis that vitamin D is associated with decreased risk of prostate cancer ; indeed , higher circulating 25(OH)D concentrations may be associated with increased risk of aggressive disease Results from the majority of studies show little association between circulating concentrations of vitamin D and prostate cancer risk , a finding that has not been demonstrated in a wider European population , however . The authors examined whether vitamin D concentrations were associated with prostate cancer risk in a case-control study nested within the European Prospect i ve Investigation into Cancer and Nutrition ( 1994–2000 ) . Serum concentrations of 25-hydroxyvitamin D were measured in 652 prostate cancer cases matched to 752 controls from 7 European countries after a median follow-up time of 4.1 years . Conditional logistic regression models were used to calculate odds ratios for prostate cancer risk in relation to serum 25-hydroxyvitamin D after st and ardizing for month of blood collection and adjusting for covariates . No significant association was found between 25-hydroxyvitamin D and risk of prostate cancer ( highest vs. lowest quintile : odds ratio = 1.28 , 95 % confidence interval : 0.88 , 1.88 ; P for trend = 0.188 ) . Subgroup analyses showed no significant heterogeneity by cancer stage or grade , age at diagnosis , body mass index , time from blood collection to diagnosis , or calcium intake . In summary , the results of this large nested case-control study provide no evidence in support of a protective effect of circulating concentrations of vitamin D on the risk of prostate cancer Laboratory and clinical data indicate an antitumor effect of 1,25(OH)2 vitamin D ( 1,25(OH)2D ) on prostate cancer . High calcium intake suppresses formation of 1,25(OH)2D from 25(OH)D , thereby decreasing the 1,25(OH)2D level . Ingestion of fructose reduces plasma phosphate transiently , and hypophosphatemia stimulates 1,25(OH)2D production . We thus conducted a prospect i ve study among 47,781 men of the Health Professionals Follow-Up Study free of cancer in 1986 to examine whether calcium and fructose intake influenced risk of prostate cancer . Between 1986 and 1994 , 1369 non-stage A1 and 423 advanced ( extraprostatic ) cases of prostate cancer were diagnosed . Higher consumption of calcium was related to advanced prostate cancer [ multivariate relative risk ( RR ) , 2.97 ; 95 % confidence interval ( CI ) , 1.61 - 5.50 for intakes > or = 2000 mg/day versus < 500 mg/day ; P , trend , 0.002 ] and metastatic prostate cancer ( RR , 4.57 ; CI , 1.88 - 11.1 ; P , trend , < 0.001 ) . Calcium from food sources and from supplements independently increased risk . High fructose intake was related to a lower risk of advanced prostate cancer ( multivariate RR , 0.51 ; CI , 0.33 - 0.80 , for intakes > 70 versus < or = 40 g/day ; P , trend , 0.007 ) . Fruit intake was inversely associated with risk of advanced prostate cancer ( RR , 0.63 ; 95 % CI , 0.43 - 0.93 ; for > 5 versus < or = 1 serving per day ) , and this association was accounted for by fructose intake . Non-fruit sources of fructose similarly predicted lower risk of advanced prostate cancer . A moderate positive association between energy-adjusted fat intake and advanced prostate cancer was attenuated and no longer statistically significant when controlled for calcium and fructose . Our findings provide indirect evidence for a protective influence of high 1,25(OH)2D levels on prostate cancer and support increased fruit consumption and avoidance of high calcium intake to reduce the risk of advanced prostate cancer Higher intakes of calcium and dairy products , a major source of dietary calcium , are reported to increase the risk of prostate cancer , potentially due to reductions in circulating vitamin D with increasing calcium intake . We prospect ively examined the association of dairy product and calcium intake with prostate cancer risk in 29,509 men , including 1,910 cases , in the Prostate , Lung , Colorectal , and Ovarian Cancer Screening Trial . We also evaluated the relation of calcium intake with serum 25-hydroxy-vitamin D [ 25(OH)D ] and 1,25-dihydroxy-vitamin D [ 1,25(OH)2D ] , in a Prostate , Lung , Colorectal , and Ovarian Trial sub study ( n = 275 ) . Dietary intake was assessed using a food frequency question naire . Baseline serum 1,25(OH)2D was determined by RIA . Greater intake of dairy products , particularly low-fat dairy products , was weakly associated with increased risk of prostate cancer [ relative risk ( RR ) , 1.12 ; 95 % confidence intervals ( CI ) , 0.97 - 1.30 ; P trend = 0.06 for > 2.75 versus ≤0.98 servings of total dairy/day ; 1.23 ( 1.07 - 1.41 ) for low-fat dairy ] . Greater dietary calcium intake was associated with increased risk of prostate cancer ( RR , 1.34 ; 95 % CI , 0.93 - 1.94 ; P trend = 0.02 for > 2,000 versus < 1,000 mg/day ) , but greater supplementary calcium intake was not associated with the risk . Associations of dairy product and dietary calcium intake were evident for nonaggressive disease ( RR , 1.20 ; 95 % CI , 0.99 - 1.46 ; P trend = 0.01 for dairy products ; 1.64 , 1.04 - 2.57 ; P trend = 0.002 for dietary calcium ) , but not aggressive disease ( RR , 1.02 ; 95 % CI , 0.81 - 1.28 for dairy products ; 0.94 , 0.49 - 1.80 for dietary calcium ) . Calcium intake was not associated with serum 25-hydroxy-vitamin D and 1,25(OH)2D concentration . In this large prospect i ve study in a prostate cancer screening trial , greater dietary intake of calcium and dairy products , particularly low-fat types , may be modestly associated with increased risks for nonaggressive prostate cancer , but was unrelated to aggressive disease . Furthermore , we found no relationship between calcium intake and circulating vitamin D. ( Cancer Epidemiol Biomarkers Prev 2007;16(12):2623–30 The objective of our study was to investigate the prevalence of prostate disease in general male population . Also , an extended analysis of medical history , behavior and hormonal analysis was performed . 1000 c and i date s were r and omly selected out of voluntary male population . 977 of those were included in the study , and 23 were rejected because of incomplete data , unwillingness to be subjected to examination and other reasons . Blood sample s were taken from all participants , and a question naire and physical examination ( with rectal exam ) were performed . Based on the results , answers and the examination all participants were divided in four groups . The prevalence of benign prostate hyperplasia was 23.1 % , of prostatitis 5.1 % and of prostate cancer 3.7 % , which is within expected reported values . Family history data provided little specific data . Significant lower urinary tract symptoms were found in both subjects with benign prostate hyperplasia and prostatitis , showing a strong overlap of symptoms . The results indicate that alcohol abuse is strongly related to subjects with prostate cancer , although this relation is not confirmed by all authors . On the hormonal scale we found higher levels of binned testosterone in our subjects with prostate cancer , what is disproved by some authors . Estrogen is found in higher levels and recent reports are showing higher levels of estrogen metabolites in prostate cancer subjects . Also we found lower levels of vitamin D in subjects with benign prostate hyperplasia and prostate cancer . Since vitamin D is known to inhibit cellular proliferation , lower levels are confirmatory , with its loss of protective role against prostate cancer . Our results suggest that male population in Croatia ( at least in Slavonia ) with prostate diseases is , with all findings taken into account , within limits as compared to population s in developed European countries , but on a lower border . Since the prevalence of investigated diseases is rising throughout Europe we could expect the same trends in our country The purpose of this study was to examine the relationship of plasma 25-hydroxyvitamin D ( 25(OH)D ) concentrations to prostate cancer within a large multiethnic cohort in Hawaii and California using a nested case-control design . The study included 329 incidents of prostate cancer of African American , Native Hawaiian , Japanese , Latino and White ancestry , and 656 controls matched on age , race/ethnicity , date /time of blood collection and fasting status . Conditional logistic regression was used to estimate odds ratios ( ORs ) and 95 % confidence intervals ( 95 % CI ) . No association with prostate cancer risk was found in an analysis based on quartiles of 25(OH)D. When clinical ly defined cutpoints were used , there was no increased risk for the lowest 25(OH)D concentration ( OR for < 20 versus 30-<50ng/ml=1.10 , 95 % CI=0.68 - 1.78 ) , while there was a suggestive increased risk for higher concentrations ( OR for 50ng/ml=1.52 , 95 % CI=0.92 - 2.51 ) . The findings from this prospect i ve study of men in the Multiethnic Cohort do not support the hypothesis that vitamin D lowers the risk of prostate cancer . Further follow-up is warranted to determine whether the findings are consistent across ethnic groups |
1,258 | 21,881,886 | Conclusions We found that STAR prosthesis achieved encouraging results in terms of intermediate to long-term outcome .
The major reasons for implant failure were aseptic loosening and malalignment .
Maybe the increase of surgeons ’ experience and patient selection could improve outcomes and decrease failure rate | Purpose The purpose of this study was to provide cumulative data about the intermediate to long-term outcome of Sc and inavian total ankle replacement ( STAR ) in the literature and to provide a summary of survival rate , implant failure rate and reasons . | Background : Mobile-bearing ankle replacements have become popular outside of the United States over the past two decades . The goal of the present study was to perform a prospect i ve evaluation of the safety and efficacy of a mobile-bearing prosthesis to treat end stage ankle arthritis . We report the results of three separate cohorts of patients : a group of Sc and anavian Total Ankle Replacement ( STAR ) patients and a control group of ankle fusion patients ( the Pivotal Study Groups ) and another group of STAR total ankle patients ( Continued Access Group ) whose surgery was performed following the completion of enrollment in the Pivotal Study . Material s and Methods : The Pivotal Study design was a non-inferiority study using ankle fusion as the control . A non-r and omized multi-centered design with concurrent fusion controls was used . We report the initial perioperative findings up to 24 months following surgery . For an individual patient to be considered an overall success , all of the following criteria needed to be met : a ) a 40-point improvement in total Buechel-Pappas ankle score , b ) no device failures , revisions , or removals , c ) radiographic success , and d ) no major complications . In the Pivotal Study ( 9/00 to 12/01 ) , 158 ankle replacement and 66 arthrodesis procedures were performed ; in the Continued Access Study ( 4/02 to 10/06 ) , 448 ankle replacements were performed , of which 416 were at minimum 24 months post-surgery at time of the data base closure . Results : Major complications and need for secondary surgical intervention were more common in the Pivotal Study arthroplasty group than the Pivotal Study ankle fusion group . In the Continued Access Group , secondary procedures performed on these arthroplasty patients decreased by half when compared with the Pivotal Arthroplasty Group . When the Pivotal Groups were compared , treatment efficacy was higher for the ankle replacement group due to improvement in functional scores . Pain relief was equivalent between fusion and replacement patients . The hypothesis of non-inferiority of ankle replacement was met for overall patient success . Conclusion : By 24 months , ankles treated with STAR ankle replacement ( in both the Pivotal and Continued Access Groups ) had better function and equivalent pain relief as ankles treated with fusion . Level of Evidence : II , Prospect i ve Controlled Comparative Surgical We describe the medium-term results of a prospect i ve study of 200 total ankle replacements at a single-centre using the Sc and inavian Total Ankle Replacement . A total of 24 ankles ( 12 % ) have been revised , 20 by fusion and four by further replacement and 27 patients ( 33 ankles ) have died . All the surviving patients were seen at a minimum of five years after operation . The five-year survival was 93.3 % ( 95 % confidence interval ( CI ) 89.8 to 96.8 ) and the ten-year survival 80.3 % ( 95 % CI 71.0 to 89.6 ) . Anterior subluxation of the talus , often seen on the lateral radiograph in osteoarthritic ankles , was corrected and , in most instances , the anatomical alignment was restored by total ankle replacement . The orientation of the tibial component , as seen on the lateral radiograph , also affects the position of the talus and if not correct can hold the talus in an abnormal anterior position . Subtalar arthritis may continue to progress after total ankle replacement . Our results are similar to those published previously We describe the results of a r and omised , prospect i ve study of 200 ankle replacements carried out between March 2000 and July 2003 at a single centre to compare the Buechel-Pappas ( BP ) and the Sc and inavian Total Ankle Replacement ( STAR ) implant with a minimum follow-up of 36 months . The two prostheses were similar in design consisting of three components with a meniscal polyethylene bearing which was highly congruent on its planar tibial surface and on its curved talar surface . However , the design s were markedly different with respect to the geometry of the articular surface of the talus and its overall shape . A total of 16 ankles ( 18 % ) was revised , of which 12 were from the BP group and four of the STAR group . The six-year survivorship of the BP design was 79 % ( 95 % confidence interval ( CI ) 63.4 to 88.5 and of the STAR 95 % ( 95 % CI 87.2 to 98.1 ) . The difference did not reach statistical significance ( p = 0.09 ) . However , varus or valgus deformity before surgery did have a significant effect ) ( p = 0.02 ) on survivorship in both groups , with the likelihood of revision being directly proportional to the size of the angular deformity . Our findings support previous studies which suggested that total ankle replacement should be undertaken with extreme caution in the presence of marked varus or valgus deformity The purpose of the current prospect i ve study was to determine the midterm results of 68 total ankle replacements with the Sc and inavian Total Ankle Replacement ( S.T.A.R. ) prosthesis . The 65 patients ( 34 women and 31 men ; mean age at surgery , 56.1 years [ range , 22 - 85 years ] ) were assessed clinical ly and radiologically after 3.7 years ( range , 2.4 - 6.2 years ) . Thirty-five patients ( 54 % ) were totally pain-free . The overall clinical score was grade d as excellent or good in 67 ankles . The American Orthopaedic Foot and Ankle Society hindfoot score improved from 24.7 points ( range , 3 - 44 points ) preoperatively to 84.3 points ( range , 44 - 100 points ) at followup . Three patients ( three ankles , 4.4 % ) had a ballooning bone lysis on the tibial side . Despite prophylaxis , periarticular hypertrophic bone formation was seen in 43 ankles ( 63 % ; 42 patients ) , associated with a decrease of dorsiflexion and plantar flexion . Nine ankles ( 13 % ; nine patients ) had revision surgery because of problems with the components and 14 ankles ( 21 % ; 14 patients ) had secondary or additional operations . All revision or secondary surgeries were successful , and no ankle had to be converted to an ankle arthrodesis . The early experience with the S.T.A.R. ankle implant is encouraging , although we have encountered more complications and potential problems than previously reported Early design s of Total Ankle Replacement ( TAR ) had a high failure rate . More recent experience with the 3-piece , meniscal bearing , total ankle replacement has been more promising . We report a review of the early results of our first 22 prostheses in 20 patients undergoing Sc and inavian Total Ankle Replacement ( STAR ) in Northern Irel and . There was a mean follow-up time of 26 months . Seventeen patients are pain-free at the ankle joint during normal daily activities . Two of the early cases have required revision surgery due to technical errors . Other complications have included malleolar fractures , poor wound healing and postoperative stiffness . These early results show high levels of patient satisfaction , and we are encouraged to continue with total ankle arthroplasty . There is a steep initial learning curve and use of TAR should be restricted to foot and ankle surgeons . ImagesFig 1Figs 2a and bFigs 2 c and Fifty-eight patients with either rheumatoid arthritis or osteoarthritis were treated with meniscal-bearing ankle prostheses . The concept was to mobilize , align , and stabilize the ankle before resurfacing it . Cement was used for prostheses fixation in 33 patients ( 1986 - 1989 ) and 25 patients had fixation without cement ( 1990 - 1995 ) . All patients in one prospect i ve series were followed up yearly with radiographs and with a clinical scoring system giving a maximum of 100 points . This allowed for a patient-controlled prospect i ve study . No patients were lost to followup . The only detectable difference in the treatment was the fixation mode . For the purpose of comparing patients with cemented and uncemented prostheses , the patients who had surgery between 1986 and 1989 were not followed up after 1997 , and patients who had surgery between 1990 and 1995 were not followed up after 2002 . The mean followup was 9.4 years . Failure was defined as prosthesis revision or change to arthrodesis for any reason . In the cemented group , nine of 33 patients had revision surgery or fusion . In the uncemented group , one of 25 patients had revision surgery . Survivorship analysis for 12 years based on life tables showed a 70 % survival rate ( confidence limit , 60.3 - 78.5 ) for the cemented group and 95.4 % survival rate ( confidence limit , 91.0 - 99.9 ) for the uncemented group . The average clinical scores at the latest followup were 74.2 + /- 19.3 for the cemented group and 91.9 + /- 7.4 points for the uncemented group . Therefore , unconstrained meniscal-bearing ankle prostheses should be uncemented The purpose of this study was to evaluate the function of the ankle joint during walking before and after Sc and inavian Total Ankle Replacement ( STAR ) . Nine patients ( six males and three females ) with an average age of 65 years , scheduled for unilateral total ankle replacement for osteoarthritis and rheumatoid arthritis , were evaluated both preoperatively and postoperatively in a gait analysis laboratory . Arthroplasty patients showed reduced range of motion at the ankle compared to normal controls . Postoperative arthroplasty subjects had significantly improved external ankle dorsiflexion moment , the moment that affects the plantarflexor muscles , when compared to their preoperative status . The moment in arthroplasty patients was increased , indicating improved function of the ankle joint One hundred consecutive cases treated with ankle arthroplasty for osteoarthritis ( OA ) or rheumatoid arthritis were followed prospect ively and annually for up to 15 years . Survivorship analysis was performed , with the endpoint being prosthesis revision or change to arthrodesis . Patients who were younger than 50 years at the first implantation constituted one group ( group A , 30 ankles ) . The other group ( group B , 70 ankles ) consisted of patients aged 50 years or older at the first implantation . All patients were assessed clinical ly according to the Kofoed Ankle Score . The distribution of OA/rheumatoid arthritis in group A was 18/12 , and in group B it was 43/27 ( not significant ) . The median age in group A was 46 years ( range , 22–49 years ) , and in group B it was 63 years ( range , 51–83 years ) . In group A , one case was revised , and three cases were converted to arthrodesis after a median of 5 years ( range , 5–9 years ) . In group B , four cases were revised , and four cases were converted to arthrodesis after a median of 5.5 years ( range , 2–8 years ) . The results of cases with traumatic OA did not differ between groups A and B. It was concluded that the results of ankle arthroplasty were of equal quality in patients younger than 50 years and those who were older An up to 12-year follow-up of 51 single-coated STAR revealed that 15 ankles had undergone fusion . The mean time from primary surgery to the first revision was median 51 months . In a series of 58 double-coated STAR ankles followed up to 5 years only one ankle had to be revised for component loosening . In this series the clinical survival rate was 98 % and the radiographic survival rate 94 % at 5 years . The radiographic survival rate , with component loosening as endpoint , was significantly better for the last 31 cases in the series of the single-coated prostheses . However , the loosening rate did not differ when these latter 31 cases were compared with the cases operated on with a double-coated prosthesis . One may conclude that improvement of the anchoring surfaces has had a limited influence on the radiographic survival of the STAR ankle . However , from the clinical survivorship figures it is obvious that the learning process continues as the difference in revision rate between the 31 last implanted single-coated and the later on implanted double-coated prostheses approached significance |
1,259 | 23,069,589 | With the increasing pressure of re sources and time , tradiional instructor led courses may not be the most efficient method or delivering resuscitation training to sharp end CPR providers .
The automated voice feedback/prompt ystem used a computer-guided manikin with automated | Deployment of 2010 revised guidelines has result ed in ndless amounts of time and energy being spent on mastering he components of CPR .
However , there are still difficulties being ncountered by people to incorporate new information into their lready established procedural memory .
Some examples of alternative mediums or delivering basic and advanced resuscitation training include : ideo self-instruction,4–6 high-fidelity simulation,7 voice advisory anikins,8 semi-interactive video9 and web-based instructions.10 articularly , self-instruction videos for CPR training have proven ffective in both lay persons9,11 and healthcare professionals.12 his educational modality was also effective in teaching AED use or lay rescuers.13 However , considerable variability exists in BLS kill acquisition and retention across many manikin-based studies valuating different educational modalities.4,5,14–16 Notably , sevral studies and a recent systematic review suggested that training sing automated CPR feedback/prompt system is effective for basic PR skill acquisition for lay rescuers , and improves the quality of PR performance on manikins by healthcare professionals.17 The current study by Mpotos et al.18 in this month ’s Resusitation serves to highlight the importance of evaluating new raining modalities in self-learning environment . | STUDY OBJECTIVE We conducted a prospect i ve , r and omized , controlled trial to test the hypothesis that a 34-minute video self-instruction ( VSI ) training program for adult CPR would yield comparable or better CPR performance than the current community st and ard , the American Heart Association Heartsaver course . METHODS Incoming freshman medical students were r and omly assigned to VSI or the Heartsaver CPR course . Two to 6 months after training , we tested subjects to determine their ability to perform CPR in a simulated cardiac arrest setting . Blinded observers used explicit criteria to assess our primary outcome , CPR performance skill . In addition , we assessed secondary outcomes including sequential performance of individual skills , ventilation and chest compression characteristics , and written tests of CPR-related knowledge and attitudes . RESULTS VSI trainees displayed superior overall performance compared with traditional trainees . Twenty of 47 traditional trainees ( 43 % ) were judged not competent in their performance of CPR , compared with only 8 of 42 VSI trainees ( 19 % ; absolute difference , 24 % ; 95 % confidence interval , 5 % to 42 % ) . CONCLUSION In a group of incoming freshman medical students , we found that a half-hour of VSI result ed in superior overall CPR performance compared with that in traditional trainees . If vali date d by further research , VSI may provide a simple , quick , and inexpensive alternative to traditional CPR instruction for health care workers and , perhaps , the general population STUDY OBJECTIVE Despite the proven efficacy of cardiopulmonary resuscitation ( CPR ) , only a small fraction of the population knows how to perform it . As a result , rates of byst and er CPR and rates of survival from cardiac arrest are low . Byst and er CPR is particularly uncommon in the African American community . Successful development of a simplified approach to CPR training could boost rates of byst and er CPR and save lives . We conducted the following r and omized , controlled study to determine whether video self-instruction ( VSI ) in CPR results in comparable or better performance than traditional CPR training . METHODS This r and omized , controlled trial was conducted among congregational volunteers in an African American church in Atlanta , GA . Subjects were r and omly assigned to receive either 34 minutes of VSI or the 4-hour American Heart Association " Heartsaver " CPR course . Two months after training , blinded observers used explicit criteria to assess CPR performance in a simulated cardiac arrest setting . A recording manikin was used to measure ventilation and chest compression characteristics . Participants also completed a written test of CPR-related knowledge and attitudes . RESULTS VSI trainees displayed a comparable level of performance to that achieved by traditional trainees . Observers scored 40 % of VSI trainees competent or better in performing CPR , compared with only 16 % of traditional trainees ( absolute difference 24 % , 95 % confidence interval 8 % to 40 % ) . Data from the recording manikin confirmed these observations . VSI trainees and traditional trainees achieved comparable scores on tests of CPR-related knowledge and attitudes . CONCLUSION Thirty-four minutes of VSI can produce CPR of comparable quality to that achieved by traditional training methods . VSI provides a simple , quick , consistent , and inexpensive alternative to traditional CPR instruction , and may be used to extend CPR training to historically underserved population BACKGROUND Byst and er CPR improves outcomes after out of hospital cardiac arrest . The length of current 4-h classes in cardiopulmonary resuscitation ( CPR ) is a barrier to more widespread dissemination of CPR training and older adults in particular are underrepresented in traditional classes . Training with a brief video self-instruction ( VSI ) program has shown that this type of training can produce short-term skill performance at least as good as that seen with traditional American Heart Association ( AHA ) Heartsaver training , although it is unclear whether there is comparable skill retention . METHODS AND RESULTS Two hundred and eight-five adults between the ages of 40 and 70 who had no CPR training within the past 5 years were assigned at r and om to a no-training control group , Heartsaver ( HS ) training , or one of three versions of brief VSI ( i.e. , self-trained-ST subjects ) . Post-training performance of CPR skills was assessed in a scenario format by human examiners and by sensored manikin at Time 1 ( immediately post-training ) and again at Time 2 ( 2 months post-training ) . Performance by controls was assessed only once . Significant ( P<.001 ) decline was observed in the three measures recorded by examiners ; assess responsiveness ( from 72 % to 60 % for HS subjects and from 90 % to 77 % for ST subjects ) , call 911 ( from 82 % to 74 % for HS subjects and from 71 % to 53 % for ST subjects ) , and overall performance ( from 42 % to 30 % for HS subjects and from 60 % to 44 % for ST subjects ) . Significant ( P<.001 ) decline was observed in two of three skills measured by a sensored manikin : ventilation volume ( from 40 % to 36 % for HS subjects and from 61 % to 41 % for ST subjects , with a significant [ P=.028 ] interaction ) and correct h and placement ( from 68 % to 59 % for HS subjects and from 80 % to 64 % for ST subjects ) . Heartsaver and self-trained subjects generally showed similar rates of decline . At Time 2 , examiners rated trained subjects better than untrained controls in all skills except calling 911 , where self-trained subjects did not differ from controls ; manikin data revealed that trained subjects ' performance was better than that of controls for ventilation volume , but had declined to the level of controls for both h and placement and compression depth . CONCLUSIONS Adults between 40 and 70 years of age who participated in a CPR VSI program experienced performance decline in their CPR skills after a post-training interval of 2 months . However , this decline was no greater than that seen in subjects who took Heartsaver training . The VSI program produced retention performance at least as good as that seen with traditional training . Additional effort is needed to improve both initial performance and retention of CPR skills . CONDENSED ABSTRACT Retention of CPR skills was compared 2 months post-training for adults between 40 and 70 years old who had taken either a traditional Heartsaver CPR course or a 22-min video self-directed training course . Although performance declines occurred in the 2-month interval , self-trained subjects generally demonstrated CPR skill retention equivalent to that of Heartsaver-trained subjects , although for both groups skill decline on some measures reached the level of untrained controls OBJECTIVES / PURPOSE To test registered nurses ' abilities to retain basic or advanced life support psychomotor skills and theoretical knowledge . DESIGN A repeated- measures , quasi-experimental design was used . METHODS Written and performance tests ( initial , post-training , and final testing ) used scenarios requiring performance of advanced cardiac life support ( ACLS ) or basic life support ( BLS ) skills . Final testing was by r and om assignment to 3 , 6 , 9 , or 12 months . SAMPLE A convenience sample ( n=133 ) was used . INSTRUMENTATION American Heart Association 2000 ACLS and BLS evaluation tools were used in a simulated testing environment . FINDINGS Findings show nurses retain theoretical knowledge but performance skills de grade quickly . ACLS skills de grade faster than BLS skills with 63 % passing BLS at 3 months and 58 % at 12 months . Only 30 % of participants passed ACLS skills at 3 months and 14 % at 12 months . These findings are similar to the results of other investigators in over a decade of research . CONCLUSIONS Study results showed a decline in skills retention with nurses unable to perform ACLS and BLS skills to st and ard for the entire certification period . The need for more frequent refresher training is needed . No formal research at this institution indicates skill degradation adversely affected patient outcomes . Further research on ACLS and BLS course content , design , management , and execution is needed INTRODUCTION The optimal strategy to retrain basic life support ( BLS ) skills on a manikin is unknown . We analysed the differential impact of a video ( video group , VG ) , voice feedback ( VFG ) , or a serial combination of both ( combined group , CG ) on BLS skills in a self-learning ( SL ) environment . METHODS Two hundred and thirteen medicine students were r and omly assigned to a VG , a VFG and a CG . The VG refreshed the skills with a practice -while-watching video ( abbreviated Mini Anne ™ video , Laerdal , Norway ) and a manikin , the VFG with a computer-guided manikin ( Resusci Anne Skills Station ™ , Laerdal , Norway ) and the CG with a serial combination of both . Each student performed two sequences of 60 compressions , 12 ventilations and three complete cycles of BLS ( 30:2 ) . The proportions of students achieving adequate skills were analysed using generalised estimating equations analysis , taking into account pre-test results and training strategy . RESULTS Complete data sets were obtained from 192 students ( 60 VG , 69 VFG and 63 CG ) . Before and after training , ≥70 % of compressions with depth ≥50 mm were achieved by 14/60 ( 23 % ) vs. 16/60 ( 27 % ) VG , 24/69 ( 35 % ) vs. 50/69 ( 73 % ) VFG and 19/63 ( 30 % ) vs. 41/63 ( 65 % ) CG ( P<0.001 ) . Compression rate 100 - 120/min was present in 27/60 ( 45 % ) vs. 52/60 ( 87 % ) VG , 28/69 ( 41 % ) vs. 44/69 ( 64 % ) VFG and 27/63 ( 43 % ) vs. 42/63 ( 67 % ) CG ( P=0.05 ) . Achievement of ≥70 % ventilations with a volume 400 - 1000 ml was present in 29/60 ( 49 % ) vs. 32/60 ( 53 % ) VG , 32/69 ( 46 % ) vs. 52/69 ( 75 % ) VFG and 25/63 ( 40 % ) vs. 51/63 ( 81 % ) CG ( P=0.001 ) . There was no between-groups difference for complete release . CONCLUSIONS Voice feedback and a sequential combination of video and voice feedback are both effective strategies to refresh BLS skills in a SL station . Video training alone only improved compression rate . None of the three strategies result ed in an improvement of complete release AIM To evaluate the retention of skills 6 months after training in ventilation and chest compressions ( CPR ) on a manikin with computer based on-line voice advisory feedback and the possible effects of initial overtraining . METHODS Thirty five volunteers had 20 min provisional CPR training on a manikin with computer based voice advisory feedback but without an instructor . The appropriate feedback was taken from a pre-recorded list depending on performance measured by the manikin -- computer system versus set limits for ventilation and compression variables . One group in addition was r and omised to receive 10 similar 3 min training sessions during 1 week in the following month ( overtrained group ) . All ventilation and compression variables were measured without feedback before and after the initial training session , with feedback immediately thereafter , and both without and with feedback 6 months after the initial training session . RESULTS The initial training improved all variables . Compressions with correct depth increased from a mean of 33 to 77 % , and correct inflations from a mean of 9 to 58 % . After 6 months , the results for the controls were not significantly different from pre-training , except for a higher of correct inflations ( 18 % ) , while the overtrained group had better retention of skills including the correct compression depth ( mean 61 % ) and inflations ( mean 42 % ) . When verbal feedback was added both the compressions and ventilations immediately improved both when tested immediately and 6 months after the initial training session . CONCLUSIONS The computer-based voice advisory manikin ( VAM ) feedback system can improve immediate performance of basic life support ( BLS ) skills , with better long-term retention with overtraining BACKGROUND Each year , more than 1.5 million health care professionals receive advanced life support ( ALS ) training . OBJECTIVE To determine whether a blended approach to ALS training that includes electronic learning ( e-learning ) produces outcomes similar to those of conventional , instructor-led ALS training . DESIGN Open-label , noninferiority , r and omized trial . R and omization , stratified by site , was generated by Sealed Envelope ( Sealed Envelope , London , United Kingdom ) . ( International St and ardized R and omized Controlled Trial Number Register : ISCRTN86380392 ) SETTING 31 ALS centers in the United Kingdom and Australia . PARTICIPANTS 3732 health care professionals recruited between December 2008 and October 2010 . INTERVENTION A 1-day course supplemented with e-learning versus a conventional 2-day course . MEASUREMENTS The primary outcome was performance in a cardiac arrest simulation test at the end of the course . Secondary outcomes comprised knowledge- and skill-based assessment s , repeated assessment after remediation training , and re source use . RESULTS 440 of the 1843 participants r and omly assigned to the blended course and 444 of the 1889 participants r and omly assigned to conventional training did not attend the courses . Performance in the cardiac arrest simulation test after course attendance was lower in the electronic advanced life support ( e-ALS ) group compared with the conventional advanced life support ( c-ALS ) group ; 1033 persons ( 74.5 % ) in the e-ALS group and 1146 persons ( 80.2 % ) in the c-ALS group passed ( mean difference , -5.7 % [ 95 % CI , -8.8 % to -2.7 % ] ) . Knowledge- and skill-based assessment s were similar between groups , as was the final pass rate after remedial teaching , which was 94.2 % in the e-ALS group and 96.7 % in the c-ALS group ( mean difference , -2.6 % [ CI , -4.1 % to 1.2 % ] ) . Faculty , catering , and facility costs were $ 438 per participant for electronic ALS training and $ 935 for conventional ALS training . LIMITATIONS Many professionals ( 24 % ) did not attend the courses . The effect on patient outcomes was not evaluated . CONCLUSION Compared with conventional ALS training , an approach that included e-learning led to a slightly lower pass rate for cardiac arrest simulation tests , similar scores on a knowledge test , and reduced costs . PRIMARY FUNDING SOURCE National Institute of Health Research and Resuscitation Council ( UK ) |
1,260 | 22,336,862 | Massage may have a role in reducing pain , and improving women 's emotional experience of labour . | BACKGROUND Many women would like to avoid pharmacological or invasive methods of pain management in labour , and this may contribute towards the popularity of complementary methods of pain management .
This review examined currently available evidence supporting the use of manual healing methods including massage and reflexology for pain management in labour .
OBJECTIVES To examine the effects of manual healing methods including massage and reflexology for pain management in labour on maternal and perinatal morbidity . | Background Reflexology is an ancient , mild and non-invasive technique , used widely as one of the non-pharmacological methods for pain relief . The aim of this research was to determine the effect of reflexology on pain intensity as well as to determine the duration of labor in primiparas . Methods In 2008 , a r and omized clinical trial study was conducted r and omly enrolling 120 parturient women with low risk pregnancy into three groups in Shahid Akbarabadi Hospital , Tehran , Iran . The first group received 40 minutes of reflexology at the beginning of active phase ( 4 - 5 cm cervical dilatation ) . Emotional support was offered for the second group in the same stage of pregnancy and with the same duration . The third group received only routine care during labor . Pain severity was evaluated with visual analogue scale ( 0 to 10 cm ) . In all groups , pregnant women were asked to evaluate the severity of pain experienced before and after intervention and also at cervical dilatations of 6 - 7 cm and 8 - 10 cm respectively . Data were collected through the numerical pain scale . Results Pain intensity at all the three stages of cervical dilatation was significantly lower in the reflexology group . During the 4 - 5 cm dilatation stage , women in the supported group reported less severe pain compared to those receiving routine care , but no significant differences at the later stages of labor . This indicates that reflexology could decrease the duration of first , second and third stages of labor . Conclusion Our findings showed that reflexology can be useful to decrease the pain intensity as well as duration of labor CONTEXT A prior national survey documented the high prevalence and costs of alternative medicine use in the United States in 1990 . OBJECTIVE To document trends in alternative medicine use in the United States between 1990 and 1997 . DESIGN Nationally representative r and om household telephone surveys using comparable key questions were conducted in 1991 and 1997 measuring utilization in 1990 and 1997 , respectively . PARTICIPANTS A total of 1539 adults in 1991 and 2055 in 1997 . MAIN OUTCOMES MEASURES Prevalence , estimated costs , and disclosure of alternative therapies to physicians . RESULTS Use of at least 1 of 16 alternative therapies during the previous year increased from 33.8 % in 1990 to 42.1 % in 1997 ( P < or = .001 ) . The therapies increasing the most included herbal medicine , massage , megavitamins , self-help groups , folk remedies , energy healing , and homeopathy . The probability of users visiting an alternative medicine practitioner increased from 36.3 % to 46.3 % ( P = .002 ) . In both surveys alternative therapies were used most frequently for chronic conditions , including back problems , anxiety , depression , and headaches . There was no significant change in disclosure rates between the 2 survey years ; 39.8 % of alternative therapies were disclosed to physicians in 1990 vs 38.5 % in 1997 . The percentage of users paying entirely out-of-pocket for services provided by alternative medicine practitioners did not change significantly between 1990 ( 64.0 % ) and 1997 ( 58.3 % ) ( P=.36 ) . Extrapolations to the US population suggest a 47.3 % increase in total visits to alternative medicine practitioners , from 427 million in 1990 to 629 million in 1997 , thereby exceeding total visits to all US primary care physicians . An estimated 15 million adults in 1997 took prescription medications concurrently with herbal remedies and /or high-dose vitamins ( 18.4 % of all prescription users ) . Estimated expenditures for alternative medicine professional services increased 45.2 % between 1990 and 1997 and were conservatively estimated at $ 21.2 billion in 1997 , with at least $ 12.2 billion paid out-of-pocket . This exceeds the 1997 out-of-pocket expenditures for all US hospitalizations . Total 1997 out-of-pocket expenditures relating to alternative therapies were conservatively estimated at $ 27.0 billion , which is comparable with the projected 1997 out-of-pocket expenditures for all US physician services . CONCLUSIONS Alternative medicine use and expenditures increased substantially between 1990 and 1997 , attributable primarily to an increase in the proportion of the population seeking alternative therapies , rather than increased visits per patient The objectives of this study is to examine the effects of neuromuscular therapy ( NMT ) on motor and nonmotor symptoms in Parkinson 's disease ( PD ) . Thirty-six subjects with PD were r and omly assigned to NMT or music relaxation ( MR , or active control ) . Subjects received treatment twice a week for 4 weeks . Testing was conducted at baseline , after final treatment , and 8 days after final treatment . Primary outcome measures were the Motor subscale of the United Parkinson Disease Rating Scale ( UPDRS ) and the Clinical Global Impression scale ( CGI-Change ) . Secondary outcome measures included a PD-specific quality of life scale ( PDQ-39 ) , quantitative measures of motor function , and severity scales for anxiety and depression symptoms . NMT result ed in a significant and sustained improvement in the Motor subscale of the UPDRS ( P < or = 0.0001 ) , most notable in the tremor scores . Also improved 1 week after the last treatment were the CGI scores ( P = 0.007 ) and the finger-tapping speed ( P = 0.001 ) . The MR active control group had a slight improvement in tremor but evidence d no other change in motor function . Both groups exhibited a modest improvement in quality of life immediately after the last treatment . This effect was sustained for 8 days only in the MR group . In the nonmotor domains , the MR group evidence d improvements in mood ( P = 0.001 ) and anxiety ( P = 0.002 ) , whereas NMT had no effect on mood ( P = 0.09 ) , and its initial effect on anxiety ( P = 0.0009 ) dissipated after 8 days ( P = 0.40 ) . Group differences for UPDRS motor score and patient CGI-Change were superior in the NMT compared to the MR group . There was no group difference in PDQ-39 scores or in nonmotor measures . The findings suggest that NMT can improve motor and selected nonmotor symptoms in PD and that this effect is more durable for the motor symptoms . The results of this pilot study warrant larger controlled studies to examine dose range , durability , and mechanisms of NMT in PD function Purpose To investigate the effects of massage and presenting an attendant on pain , anxiety and satisfaction during labor to clarify some aspects of using an alternative complementary strategy . Methods 120 primiparous women with term pregnancy were divided into massage , attendant and control groups r and omly . Massage group received firm and rhythmic massage during labor in three phases . After 30 min massage at each stage , pain , anxiety and satisfaction levels were evaluated . Self-reported present pain intensity scale was used to measure the labor pain . Anxiety and satisfaction were measured with the st and ard visual analog scale . Results Massage group had lower pain state in second and third phases ( p < 0.05 ) in comparison with attendant group but reversely , the level of anxiety was lower in attendant group in second and third phases ( p < 0.05 ) and satisfaction was higher in massage group in all four phases ( p < 0.001 ) . The massage group had lower pain and anxiety state in three phases in comparison with control group ( p < 0.05 ) . Data analysis of satisfaction level showed higher values in four phases in massage group compared with control ( p < 0.001 ) and comparison of attendant and control groups showed higher satisfaction in attendant group in phases 2 , 3 and 4 as well ( p < 0.001 ) . Duration of active phase was lower in massage group ( p < 0.001 ) . Conclusions Findings suggest that massage is an effective alternative intervention , decreasing pain and anxiety during labor and increasing the level of satisfaction . Also , the supportive role of presenting an attendant can positively influence the level of anxiety and satisfaction QUESTION Does massage relieve pain in the active phase of labour ? DESIGN R and omised trial with concealed allocation , assessor blinding for some outcomes , and intention-to-treat analysis . PARTICIPANTS 46 women pregnant at ≥ 37 weeks gestation with a single fetus , with spontaneous onset of labour , 4 - 5 cm of cervical dilation , intact ovular membranes , and no use of medication after admission to hospital . INTERVENTION Experimental group participants received a 30-min lumbar massage by a physiotherapist during the active phase of labour . A physiotherapist attended control group participants for the same period but only answered questions . Both groups received routine perinatal care . OUTCOME MEASURES The primary outcome was pain severity measured on a 100 mm visual analogue scale . Secondary outcomes included the Short Form McGill Pain Question naire , pain location , and time to analgesic medication use . After labour , a blinded research er also recorded duration of labour , route of delivery , neonatal outcomes , and the participant 's satisfaction with the physiotherapist during labour . RESULTS At the end of the intervention , pain severity was 52 mm ( SD 20 ) in the experimental group and 72 mm ( SD 15 ) in control group , which was significantly different with a mean difference of 20 mm ( 95 % CI 10 to 31 ) . The groups did not differ significantly on the other pain-related outcome measures . Obstetric outcomes were also similar between the groups except the duration of labour , which was 6.8hr ( SD 1.6 ) in the experimental group and 5.7hr ( SD 1.5 ) in the control group , mean difference 1.1hr ( 95 % CI 0.2 to 2.0 ) . Patients in both groups were satisfied with the care provided by the physiotherapist . CONCLUSION Massage reduced the severity of pain in labour , despite not changing its characteristics and location Background : Labor pain is one of the severest pains that cause many women request cesarean section for fear of pain . Thus , controlling labor pain is a major concern of maternity care . Nowadays , interest in non-pharmacological pain relief methods has been increased because of their lower side effects . The effects of discrete heat and cold on decreasing labor pain have been reported but there was no evaluation of the effects of simultaneous heat and cold . The aim of this study was to investigate the effect of intermittent heat and cold on pain severity and childbirth outcomes . Material s and Methods : This study was a r and omized controlled trial . Sixty-four nulliparous women with term , One fetus , and low-risk pregnancy were divided into the intervention ( 32 participants ) and the control group ( 32 participants ) by r and om allocation . Excluding criteria were : administration of pain relief drugs , skin disease in the field of intervention , fetal distress , bleeding , fever , and disagreement with participation in the study . Warm and cold packs were used intermittently on low back and lower abdomen during the first phase and on perineum during the second phase of labor . Pain intensity was assessed with Visual Analogue Scale . Descriptive statistic , chi square , and t-test were used for data analysis . Results : There were no significant differences in demographic and midwifery characteristics and the baseline pain between two groups . The pain was significantly lower in intervention group during the first and second phases of labor . Duration of the first and third phases of labor was shorter in the case group . There were no significant differences in type of delivery , perineal laceration , oxytocin uptake , fetal heart rate , and APGAR between two groups . Discussion : Local warming with intermittent cold pack can reduce labor pain without adverse effects on maternal and fetal outcomes . It is an inexpensive and simple method . Conclusion : Intermittent local heat and cold therapy is a no pharmalogical , safe and effective method to relief labor pain OBJECTIVE To determine the effect of breathing techniques and nurse-administered massage on the pain perception of pregnant woman during labour . SETTING AND PARTICIPANTS The present study was conducted among pregnant women ( 75 % primiparous ) admitted to the SSK Bakirkoy Women and Children 's Hospital ( Istanbul , Turkey ) between January 1 , and September 1 , 2000 . The patients were in their 38th to 42nd week of pregnancy , not at high risk and expected to have normal vaginal delivery . They were selected from volunteers by nonr and om sampling . STUDY DESIGN The present study involved 40 cases , with 20 in the experimental group and 20 in the control group . Data were obtained through the visual analogue scale , inspection form , observation form and postnatal interview form . The study investigators provided information about labour , breathing techniques and massage to the pregnant women assigned to the experimental group at the beginning of labour ( latent phase ) . A study investigator also accompanied them during labour . These women received nurse-administered massage and were encouraged to breathe and perform self-administered massage . They were also instructed to change their positions and to relax . RESULTS AND CONCLUSION Study results demonstrated that nursing support and patient-directed education concerning labour and nonpharmacological pain control methods ( eg , breathing and cutaneous stimulation techniques ) were effective in reducing the perception of pain by pregnant women ( when provided in the latent labour phase before delivery ) , leading to a more satisfactory birth experience AIM Reduction of labor pain is one of the most important aspects of obstetric care . Heat therapy , typically applied to the woman 's back , lower abdomen , groin , and /or perineum during last stage of labor , is an easy pain relief method that does not require highly skilled care . The effectiveness of heat therapy applied to the perineum during the first stage of labor has not been evaluated . This study aim ed to evaluate the effectiveness of heat therapy for pain and woman 's satisfaction during physiological labor . SUBJECTS AND METHODS Sixty primiparous women aged 18 - 35 years old were r and omly assigned to heat therapy and control groups . Pain and satisfaction scores were measured by visual analog scale . The measurements of satisfaction were accomplished after birth . Data were analyzed by using the t-test and chi-square RESULTS Mean pain scores in the heat therapy group were significantly lower than the control group ( P < 0.05 ) . The mean satisfaction score in the heat therapy group was significantly higher than in the control group ( P < 0.05 ) . CONCLUSION Heat therapy , an inexpensive complementary treatment with low risk , can reduce the intensity of pain and increase mothers ' satisfaction with care during the active phase of labor In this article the positive effects of massage therapy on biochemistry are review ed including decreased levels of cortisol and increased levels of serotonin and dopamine . The research review ed includes studies on depression ( including sex abuse and eating disorder studies ) , pain syndrome studies , research on auto-immune conditions ( including asthma and chronic fatigue ) , immune studies ( including HIV and breast cancer ) , and studies on the reduction of stress on the job , the stress of aging , and pregnancy stress . In studies in which cortisol was assayed either in saliva or in urine , significant decreases were noted in cortisol levels ( averaging decreases 31 % ) . In studies in which the activating neurotransmitters ( serotonin and dopamine ) were assayed in urine , an average increase of 28 % was noted for serotonin and an average increase of 31 % was noted for dopamine . These studies combined suggest the stress-alleviating effects ( decreased cortisol ) and the activating effects ( increased serotonin and dopamine ) of massage therapy on a variety of medical conditions and stressful experiences The use of osteopathic manipulative treatment ( OMT ) during pregnancy has a long tradition in osteopathic medicine . A retrospective study was design ed to compare a group of women who received prenatal OMT with a matched group that did not receive prenatal OMT . The medical records of 160 women from four cities who received prenatal OMT were review ed for the occurrence of meconium-stained amniotic fluid , preterm delivery , use of forceps , and cesarean delivery . The r and omly selected records of 161 women who were from the same cities , but who did not receive prenatal OMT , were review ed for the same outcomes . The results of a logistic regression analysis were statistically reliable , chi2 ( 4 , N = 321 ) = 26.55 ; P < .001 , indicating that the labor and delivery outcomes , as a set , were associated with whether OMT was administered during pregnancy . According to the Wald criterion , prenatal OMT was significantly associated with meconium-stained amniotic fluid ( Z = 13.20 , P < .001 ) and preterm delivery ( Z = 9.91 ; P < .01 ) , while the use of forceps was found to be marginally significant ( Z = 3.28 ; P = .07 ) . The case control study found evidence of improved outcomes in labor and delivery for women who received prenatal OMT , compared with women who did not . A prospect i ve study is proposed as the next step in evaluating the effects of prenatal OMT Research on massage therapy for maternal pain and anxiety in labour is currently limited to four small trials . Each used different massage techniques , at different frequencies and duration s , and relaxation techniques were included in three trials . Given the need to investigate massage interventions that complement maternal neurophysiological adaptations to labour and birth pain(s ) , we design ed a pilot r and omised controlled trial ( RCT ) to test the effects of a massage programme practised during physiological changes in pain threshold , from late pregnancy to birth , on women 's reported pain , measured by a visual analogue scale ( VAS ) at 90 min following birth . To control for the potential bias of the possible effects of support offered within preparation for the intervention group , the study included 3 arms -- intervention ( massage programme with relaxation techniques ) , placebo ( music with relaxation techniques ) and control ( usual care ) . The placebo offered a non-pharmacological coping strategy , to ensure that use of massage was the only difference between intervention and placebo groups . There was a trend towards slightly lower mean pain scores in the intervention group but these differences were not statistically significant . No differences were found in use of pharmacological analgesia , need for augmentation or mode of delivery . There was a trend towards more positive views of labour preparedness and sense of control in the intervention and placebo groups , compared with the control group . These findings suggest that regular massage with relaxation techniques from late pregnancy to birth is an acceptable coping strategy that merits a large trial with sufficient power to detect differences in reported pain as a primary outcome measure & NA ; The purpose of this study was to describe the characteristics of pain during labor with and without massage . Sixty primiparas in labor were r and omly assigned to either a massage or control group and tested using the self-reported Short-Form McGill Pain Question naire ( SF-MPQ ) at 3 phases of cervical dilation : phase 1 dilation ( 3 - 4 cm ) , phase 2 dilation ( 5 - 7 cm ) , and phase 3 dilation ( 8 - 10 cm ) . The massage group received st and ard nursing care and massage intervention , whereas the control group received st and ard nursing care only . The results of this study showed : ( 1 ) In both groups , as cervical dilation increased , there were significant increases in pain intensity as measured by SF-MPQ ; ( 2 ) massage lessened pain intensity at phase 1 and phase 2 , but there were no significant differences between the groups at phase 3 ; ( 3 ) the most frequently selected five sensory words chosen by both groups were similar at phases 1 and 2-(a ) sore , ( b ) sharp , ( c ) heavy , ( d ) throbbing , and ( e ) cramping , while of the 4 affective classes , “ fearful ” and “ tiring-exhausting ” were the most used by participants to describe the affective dimension . The results of this study indicate that , although massage can not change the characteristics of pain experienced by women in labor , it can effectively decrease labor pain intensity at phase 1 and phase 2 of cervical dilation during labor . Nurses and caregivers could consider using massage to help laboring women through the labor pain Background : During labor , women experience a high level of intense , stressful and steady pain that may negatively affect both mothers and neonates . Painkillers have previously been used for childbearing women , but nowadays , owing to some well-known limitations and serious side effects , nonpharmacologic methods such as massage and music therapies are being broadly recommended . The present clinical trial was conducted to compare the effects of massage and music therapies on the severity of labor pain in the Ilam province of western Iran . Material s & Methods : Overall , 101 primigravidae who were hospitalized for vaginal delivery were recruited and r and omly stratified into two groups of either massage ( n = 51 ) or music ( n = 50 ) therapies . Pain was measured using the visual analog scale and the two groups were compared in terms of pain severity before and after the interventions . Results : Mothers in the massage therapy group had a lower level of pain compared with those in the music therapy group ( p = 0.009 ) . A significant difference was observed between the two groups in terms of pain severity after intervention ( p = 0.01 ) . Agonizing , or most severe , labor pain was significantly relieved after massage therapy ( p = 0.001 ) . Conclusion : Massage therapy was an effective method for reducing and relieving labor pain compared with music therapy and can be clinical ly recommended as an alternative , safe and affordable method of pain relief where using either pharmacological or nonpharmacological methods are optional Twenty-eight women were recruited from prenatal classes and r and omly assigned to receive massage in addition to coaching in breathing from their partners during labor , or to receive coaching in breathing alone ( a technique learned during prenatal classes ) . The massaged mothers reported a decrease in depressed mood , anxiety and pain , and showed less agitated activity and anxiety and more positive affect following the first massage during labor . In addition , the massaged mothers had significantly shorter labors , a shorter hospital stay and less postpartum depression AIMS To investigate the effects of massage on pain reaction and anxiety during labour . BACKGROUND Labour pain is a challenging issue for nurses design ing intervention protocol s. Massage is an ancient technique that has been widely employed during labour , however , relatively little study has been undertaken examining the effects of massage on women in labour . METHODS A r and omized controlled study was conducted between September 1999 and January 2000 . Sixty primiparous women expected to have a normal childbirth at a regional hospital in southern Taiwan were r and omly assigned to either the experimental ( n=30 ) or the control ( n=30 ) group . The experimental group received massage intervention whereas the control group did not . The nurse-rated present behavioural intensity ( PBI ) was used as a measure of labour pain . Anxiety was measured with the visual analogue scale for anxiety ( VASA ) . The intensity of pain and anxiety between the two groups was compared in the latent phase ( cervix dilated 3 - 4 cm ) , active phase ( 5 - 7 cm ) and transitional phase ( 8 - 10 cm ) . RESULTS In both groups , there was a relatively steady increase in pain intensity and anxiety level as labour progressed . A t-test demonstrated that the experimental group had significantly lower pain reactions in the latent , active and transitional phases . Anxiety levels were only significantly different between the two groups in the latent phase . Twenty-six of the 30 ( 87 % ) experimental group subjects reported that massage was helpful , providing pain relief and psychological support during labour . CONCLUSIONS Findings suggest that massage is a cost-effective nursing intervention that can decrease pain and anxiety during labour , and partners ' participation in massage can positively influence the quality of women 's birth experiences BACKGROUND Childbirth is arguably one of the most painful experiences women undergo during their lives . This study aim ed to compare the effects of ice massage , acupressure and placebo in reducing the intensity of labor pain in pregnant women from selected hospitals in Tehran , Iran . METHODS A quasi-experimental study was conducted on 90 pregnant women referred from selected hospitals in Tehran . Mean age of the participants was 27.82 ± 6.20 years . Subjects were r and omly divided into three groups ( n = 30 ) to receive ice massage , acupressure or placebo . The intervention was applied at the Hegu point and pain intensity assessed using a visual analogue scale ( VAS ) before the intervention , immediately 30 min and 1 h after the intervention . RESULTS Comparing pain intensity immediately , 30 min and 1 h post-intervention across the three groups showed a significant difference between the groups . At 30 min post-intervention ( p < 0.05 ) . A Tukey test showed this difference was related to ice massage . CONCLUSION Ice massage and acupressure techniques reduced pain during labor . However , ice massage provided more persistent pain relief . Due to high levels of pain intensity and increased pain experienced by the women during the active phase of labor , it is suggested that repeating these techniques during the first stage of labor could be an effective , accessible , cost-effective and non-invasive technique to help reduce the intensity of labor pain AIMS AND OBJECTIVES ( 1 ) To evaluate the influence of local cold on severity of labour pain and ( 2 ) to identify the effect of local cold on maternal and neonatal outcomes . BACKGROUND Fear of labour pain results in an increase in pain and duration of labour , maternal discontent and dem and for caesarean section . Regarding maternal and foetal complications of analgesic medications , the attention to application of nonpharmacological methods including cold therapy is increased . DESIGN R and omised controlled trial . METHODS Sixty-four pregnant women , at initiation of active phase of labour , were allocated r and omly to cold therapy and control groups ( n = 64 ) . Null parity , term pregnancy , presence of single foetus , cephalic presentation and completing informed consent were considered as inclusion criteria . Administration of analgesic and anaesthesia , foetal distress , skin lesions in regions of cold therapy and high-risk pregnancy provided exclusion criteria . Cold pack was applied over abdomen and back , for 10 minutes every 30 minutes during first phase of labour . Additionally , cold pack was placed over perineum , for 5 minutes every 15 minutes during second phase . Pain severity was assessed based on the visual analogue scale . RESULTS The two groups were not significantly different considering demographic data , gestational age , foetal weight , rupture of membranes and primary severity of pain . Degree of pain was lower in cold therapy group during all parts of active phase and second stage . Duration of all phases was shorter in cold therapy group in all phases . Foetal heart rate , perineal laceration , type of birth , application of oxytocin and APGAR score were not significantly different between two groups . CONCLUSION Labour pain is probably reduced based on gate theory using cold . Pain control by cold maybe improves labour progression without affecting mother and foetus adversely . RELEVANCE TO CLINICAL PRACTICE Local cold therapy could be included in labour pain management |
1,261 | 30,102,781 | METHOD Electronic data bases were queried for review s of neurocognitive domains ( i.e. , inhibitory control , decision-making , central coherence , set-shifting , working memory , and attention bias ) in EDs , which identified 28 systematic and meta-analytic review s. RESULTS Broadly , the literature indicates deficits across these neurocognitive domains in EDs , though heterogeneity was noted in the magnitude of these effects , which varied to some extent across ED subtypes , sample characteristics , and method ological approaches . | OBJECTIVE In recent years there has been increasing clinical and empirical interest in neurocognitive functioning in eating disorders ( EDs ) , which has result ed in numerous quantitative and qualitative review s. However , there has yet to be a comprehensive synthesis or critical review of this literature to identify future directions to advance the field in this area .
Therefore the aim of this systematic review of systematic review s was to ( a ) characterize the existing literature on neurocognitive functioning in EDs based on recent review s ( i.e. , published since 2010 ) , ( b ) describe related limitations , and ( c ) suggest avenues for future research to address gaps in the current literature . | 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 Four experiments explored the interrelations between working memory , attention , and eye movements . Observers had to identify a tilted line amongst vertical distractors . Each line was surrounded by a colored shape that could be precued by a matching item held in memory . Relative to a neutral baseline , in which no shapes matched the memory item , search was more efficient when the memory cue matched the shape containing the target , and it was less efficient when the cued stimulus contained a distractor . Cuing affected the shortest reaction times and the first saccade in search . The effect occurred even when the memory cue was always invalid but not when the cue did not have to be held in memory . There was also no evidence for priming effects between consecutive trials . The results suggest that there can be early , involuntary top-down directing of attention to a stimulus matching the contents of working memory Because there have been few longitudinal investigations of integrative etiological theories of bulimia nervosa , this study prospect ively tested the dual-pathway model using r and om regression growth curve models and data from a 3-wave community sample of adolescent girls ( N = 231 ) . Initial pressure to be thin and thin-ideal internalization predicted subsequent growth in body dissatisfaction , initial body dissatisfaction predicted growth in dieting and negative affect , and initial dieting and negative affect predicted growth in bulimic symptoms . There was prospect i ve evidence for most of the hypothesized mediational effects . Results are consistent with the assertion that pressure to be thin , thin-ideal internalization , body dissatisfaction , dieting , and negative affect are risk factors for bulimic pathology and provide support for the dual-pathway model BACKGROUND Attention bias modification treatment ( ABMT ) is a novel treatment for anxiety disorders . Although a number of other meta-analytic review s exist , the purpose of the present meta- analysis is to examine issues unaddressed in prior review s. Specifically , the review estimates the efficacy of ABMT in clinical ly anxious patients and examines the effect of delivery context ( clinic vs. home ) on symptom reduction . METHODS A literature search using PsychInfo and Web of Science data bases was performed . Only r and omized controlled trials ( RCTs ) examining dot-probe-based ABMT in clinical ly diagnosed anxious patients were included . From 714 articles located through the search , 36 ABMT studies were identified and 11 studies met inclusion criteria ( N = 589 patients ) . RESULTS ABMT was associated with greater clinician-rated reductions in anxiety symptoms relative to control training : between-groups effect ( d = 0.42 , P = .001 , confidence interval ( CI ) = 0.18 - 0.66 ) , contrast of within-group effects ( Q = 7.25 , P < .01 ) . More patients in the treatment group no longer met formal diagnostic criteria for their anxiety disorder posttreatment relative to patients in the control condition ( P < .05 ) . Analyses of patients ' self-reported anxiety were nonsignificant for the between-groups contrast ( P = .35 ) , and were at a trend level of significance for the contrast between the within-group effects ( P = .06 ) . Moderation analysis of the between-groups effect revealed a significant effect for ABMT delivered in the clinic ( d = 0.34 , P = 0.01 , CI = 0.07 - 0.62 ) , and a nonsignificant effect for ABMT delivered at home ( d = -0.10 , P = 0.40 , CI = -0.33 - 0.13 ) . CONCLUSIONS The current meta- analysis provides support for ABMT as a novel evidence d-based treatment for anxiety disorders . Overall , ABMT effects are mainly evident when it is delivered in the clinic and when clinical outcome is evaluated by a clinician . More RCTs of ABMT in specific anxiety disorders are warranted |
1,262 | 31,768,692 | In this meta- analysis , elevated serum levels of alkaline phosphatase were associated with an increased risk of overall mortality and disease progression in patients with hormone-sensitive prostate cancer .
In contrast , those were not associated with an increased risk of cancer-specific mortality .
Alkaline phosphatase was independently associated with overall survival in both patients with “ high-volume ” and “ low-volume ” hormone-sensitive prostate cancer . | To assess the prognostic value of alkaline phosphatase in patients with hormone-sensitive prostate cancer . | One hundred thirty patients with high grade osteosarcoma were enrolled in a r and omized prospect i ve multidisciplinary treatment that included intraarterial chemotherapy , local irradiation , limb salvage surgery , and prophylactic whole lung irradiation . The patients were evaluated to stage the prognostic factors . In a multivariate analysis , a minimal level of serum lactic acid dehydrogenase less than 300 IU/L showed a significant prognostic value . The history of trauma before diagnosis of disease , local irradiation of the affected site , histologic response to preoperative multidisciplinary therapy , and prophylactic whole lung irradiation were associated with significantly better prognosis in the log rank test . Patient age , site of the primary tumor , presentation of fracture , pathologic subtype , signs and symptoms , serum alkaline phosphatase level , and erythrocyte sedimentation rate were not found to be prognostic factors . The 9-year survival rate of the whole group was 55 % |
1,263 | 32,021,476 | The keywords , such as " Screw versus Cement Retained Fixed Implant Supported Reconstructions , " " Screw Retained Fixed Implant . " "
Results No significant difference was found between the screw-retained and cemented retained implant supported reconstructions .
Dental implants are associated with complications leading to implant failure based on the type of restoration that is being used ; cement-retained restoration and screw-retained restoration .
Conclusion Screw-retained implant-supported reconstructions were found to pose less biological and technological complications .
Retention of the tooth is more stable and functional when implantation is selected based on the efficiency of a treatment procedure | Purpose Dental implant is an effective and st and ardized treatment procedure in the healthcare setting .
This study presents a comparison of dental implant reconstruction using screw and cement .
It explicitly review s the studies concerning cement and screws dental implants to determine the efficiency of the two . | OBJECTIVE The purpose of this prospect i ve clinical study was to evaluate peri-implant soft-tissue conditions and esthetic fulfillment during a 3-year follow-up period following prosthetic rehabilitation . MATERIAL AND METHODS As part of a prospect i ve multi-center study , 152 ITI dental implants were placed in 80 patients in the maxillary anterior region . Fifty-nine crowns ( 38.82 % ) were cement retained , while 93 ( 61.18 % ) crowns were screw retained . At loading and 3 , 6 , 12 and 36 months post-loading , modified plaque index ( MPI ) , sulcus bleeding index ( SBI ) , keratinized mucosa ( KM ) , gingival level ( GL ) , and esthetic fulfillment were recorded . RESULTS All patients completed the study and no complications were reported . While statistically not significant at all time points , cement-retained crowns seemed to present a worsening trend in MPI and SBI scores . Interestingly , screw-retained crowns seemed to present an opposite picture , their MPI and SBI scores improved over time . While plaque accumulation , prophylaxis and depth of crown margin significantly affected levels of sulcus bleeding , prophylaxis alone played a key role in reducing plaque accumulation . No soft tissue recession was observed in either cement- or screw-retained crowns up to 3 years post-loading . Esthetic fulfillment survey revealed that patients did not have a preference for crown types ; however , dentists favored cement-retained over screw-retained crowns . CONCLUSIONS Peri-implant soft tissues responded more favorably to screw-retained crowns when compared with cement-retained crowns . However , no soft-tissue recession was observed in either type of crowns . Cement-retained crowns were preferred by dentists , while patients were equally satisfied with either type of crowns they received The aim of the present study was to identify the peri-implant conditions ( bleeding on probing ( BOP ) , pocket probing depth ( PPD ) , modified plaque index ( mPI ) ) and marginal bone loss ( MBL , marginal bone level change between follow-up and occlusal loading ) around cemented and screw-retained posterior single crowns on tissue-level implants . The study was a retrospective cohort study with up to 4 years ( mean 2.5 years ) follow-up . Patients with either cemented or screw-retained crowns in posterior regions were included . Implant survival , technical complications , BOP , PPD , mPI , MBL , biologic complications ( peri-implant mocositis and peri-implantitis ) were evaluated . Mann-Whitney U test was used to test the difference between the screw-retained group ( SG ) and cemented group ( CG ) . 176 patients ( SG : 94 , CG : 82 ) were included . The implant survival rates were 100 % in SG and 98.8 % in CG . Prosthetic screw loosening was found in 8 restorations ( 8.7 % ) at follow-up visit . Peri-implant mucositis rate was significantly higher in the SG group ( 42.1 % ) than that in the CG group ( 32.2 % ) ( P = 0.04 ) . Six patients ( 6.38 % ) in the screw-retained group and 5 patients ( 6.10 % ) in the cemented group were diagnosed with peri-implantitis , the difference did not reach statistical significance ( P>0.05 ) . No significant difference of PPD , mPI and MBL were found between two groups ( P = 0.11 , 0.13 and 0.08 , respectively ) . High implant survival rates were achieved in both groups . Cemented single crowns on tissue-level implants showed comparable peri-implant conditions in comparison with two-piece screw-retained crowns . Well- design ed prospect i ve cohort or r and omized controlled clinical trials with longer follow-up are needed to confirm the result PURPOSE The aim of this study was to evaluate the survival and success of screw-retained versus cement-retained implant restorations in immediately loaded implants at 8-year follow-up . MATERIAL S AND METHODS Patients who were scheduled for full-arch ceramic prosthetic restorations were divided into two groups by r and omization : in one group , prosthetic frameworks were screwed onto implants ( screw-retained group , SRG ) , and in the second group , the frameworks were cemented on abutments ( cement-retained group , CRG ) . Dental implants were placed both in post extraction and in healed sites . A temporary full-arch prosthesis was placed immediately after implant placement . Intraoral digital radiographic examinations ( evaluating marginal bone levels ) were made at baseline , 6 months , and each year after implant placement . RESULTS In 28 patients , 24 full arches and 192 implants were placed in the maxilla and 10 full arches and 80 implants in the m and ible ( 17 rehabilitations in each group ) . After an 8-year follow-up period , a survival rate of 99.27 % was reported for all implants . Within the first year after implant placement , bone loss was recorded as follows : the CRG showed mean bone levels of -1.23 ± 0.45 mm , while the SRG showed mean bone levels of -1.01 ± 0.33 mm . After a 3-year follow-up , a slight increase was found ( 0.30 ± 0.25 mm in CRG and 0.45 ± 0.29 mm in SRG ) . After that point , marginal bone levels remained stable over time , up to the 8-year follow-up . No statistically significant differences were found between groups ( P > .05 ) . CONCLUSION Definitive cement- and screw-retained ceramic restorations are highly predictable , biocompatible , and esthetically pleasing , and the two groups presented no statistically significant differences in bone loss PURPOSE The purpose of this controlled prospect i ve clinical study was to compare cemented and screw-retained implant-supported single-tooth crowns followed for 4 years following prosthetic rehabilitation with respect to peri-implant marginal bone levels , peri-implant soft tissue parameters , and prosthetic complications . MATERIAL S AND METHODS Twelve consecutive patients were selected from a patient population attending the Implantology Department at the University of Padova . They all presented with single-tooth bilateral edentulous sites in the canine/premolar/molar region with adequate bone width , similar bone height at the implant sites , and an occlusal scheme that allowed for the establishment of identical occlusal cusp/fossa contacts . Each patient received 2 identical implants ( 1 in each edentulous site ) . One was r and omly selected to be restored with a cemented implant-supported single-tooth crown , and the other was restored with a screw-retained implant-supported single-tooth crown . Data on peri-implant marginal bone levels and on soft tissue parameters were collected 4 years after implant placement and analyzed to determine whether there was a significant difference with respect to the method of retention ( cemented versus screw-retained ) . RESULTS All patients completed the study . All 24 implants survived , result ing in a cumulative implant success rate of 100 % . Statistical analysis revealed no significant differences between the 2 groups with respect to peri-implant marginal bone levels and soft tissue parameters . DISCUSSION The data obtained with this study suggested that the choice of cementation versus screw retention for single-tooth implant restorations is likely not based on clinical results but seems to be based primarily on the clinician 's preference . CONCLUSIONS Within the limitations of this study , the results indicate that there was no evidence of different behavior of the peri-implant marginal bone and of the peri-implant soft tissue when cemented or screw-retained single-tooth implant restorations were provided for this patient population |
1,264 | 27,831,982 | Conclusions : All 4 treatments provided some benefit to patients with chronic LBP .
According to the MTC analysis , TDR may be the most effective treatment and PT the least effective treatment for chronic LBP .
This review is based on a limited number of RCT studies and does not support any 1 treatment modality for all patients | Objective : To determine current treatment options of chronic low back pain ( LBP ) as defined by r and omized controlled trials ( RCTs ) and to compare effectiveness of those treatments using a mixed-treatment comparison ( MTC ) .
Summary of Background Data : It is important to provide an evidence -based assessment of the treatment options that exist for LBP . | Study Design . Single blind r and omized study . Objectives . To compare the effectiveness of lumbar instrumented fusion with cognitive intervention and exercises in patients with chronic low back pain and disc degeneration . Summary of Background Data . To the authors ’ best knowledge , only one r and omized study has evaluated the effectiveness of lumbar fusion . The Swedish Lumbar Spine Study reported that lumbar fusion was better than continuing physiotherapy and care by the family physician . Patients and Methods . Sixty-four patients aged 25–60 years with low back pain lasting longer than 1 year and evidence of disc degeneration at L4–L5 and /or L5–S1 at radiographic examination were r and omized to either lumbar fusion with posterior transpedicular screws and postoperative physiotherapy , or cognitive intervention and exercises . The cognitive intervention consisted of a lecture to give the patient an underst and ing that ordinary physical activity would not harm the disc and a recommendation to use the back and bend it . This was reinforced by three daily physical exercise sessions for 3 weeks . The main outcome measure was the Oswestry Disability Index . Results . At the 1-year follow-up visit , 97 % of the patients , including 6 patients who had either not attended treatment or changed groups , were examined . The Oswestry Disability Index was significantly reduced from 41 to 26 after surgery , compared with 42 to 30 after cognitive intervention and exercises . The mean difference between groups was 2.3 ( −6.7 to 11.4 ) ( P = 0.33 ) . Improvements inback pain , use of analgesics , emotional distress , life satisfaction , and return to work were not different . Fear-avoidance beliefs and fingertip-floor distance were reduced more after nonoperative treatment , and lower limb pain was reduced more after surgery . The success rateaccording to an independent observer was 70 % after surgery and 76 % after cognitive intervention and exercises . The early complication rate in the surgical group was 18 % . Conclusion . The main outcome measure showed equal improvement in patients with chronic low back pain and disc degeneration r and omized to cognitive intervention and exercises , or lumbar fusion Study Design . A prospect i ve , r and omized , multicenter , Food and Drug Administration-regulated Investigational Device Exemption clinical trial . Objective . To evaluate the safety and effectiveness of the ProDisc ® -L ( Synthes Spine , West Chester , PA ) lumbar total disc replacement compared to circumferential spinal fusion for the treatment of discogenic pain at 1 vertebral level between L3 and S1 . Summary of Background Data . As part of the Investigational Device Exemption clinical trial , favorable single center results of lumbar total disc replacement with the ProDisc ® -L have been reported previously . Methods . Two hundred eighty-six ( 286 ) patients were treated on protocol . Patients were evaluated before and after surgery , at 6 weeks , 3 , 6 , 12 , 18 , and 24 months . Evaluation at each visit included patient self- assessment s , physical and neurologic examinations , and radiographic evaluation . Results . Safety of ProDisc ® -L implantation was demonstrated with 0 % major complications . At 24 months , 91.8 % of investigational and 84.5 % of control patients reported improvement in the Oswestry Low Back Pain Disability Question naire ( Oswestry Disability Index [ ODI ] ) from preoperative levels , and 77.2 % of investigational and 64.8 % of control patients met the ≥15 % Oswestry Disability Index improvement criteria . Overall neurologic success in the investigational group was superior to the control group ( 91.2 % investigational and 81.4 % control ; P = 0.0341 ) . At 6 weeks and 3 months follow-up time points , the ProDisc ® -L patients recorded SF-36 Health Survey scores significantly higher than the control group ( P = 0.018 , P = 0.0036 , respectively ) . The visual analog scale pain assessment showed statistically significant improvement from preoperative levels regardless of treatment ( P < 0.0001 ) . Visual analog scale patient satisfaction at 24 months showed a statistically significant difference favoring investigational patients over the control group ( P = 0.015 ) . Radiographic range of motion was maintained within a normal functional range in 93.7 % of investigational patients and averaged 7.7 ° . Conclusions . ProDisc ® -L has been found to be safe and efficacious . In properly chosen patients , ProDisc ® -L has been shown to be superior to circumferential fusion by multiple clinical criteria Mixed treatment comparison ( MTC ) meta- analysis is a generalization of st and ard pairwise meta- analysis for A vs B trials , to data structures that include , for example , A vs B , B vs C , and A vs C trials . There are two roles for MTC : one is to strengthen inference concerning the relative efficacy of two treatments , by including both ' direct ' and ' indirect ' comparisons . The other is to facilitate simultaneous inference regarding all treatments , in order for example to select the best treatment . In this paper , we present a range of Bayesian hierarchical models using the Markov chain Monte Carlo software WinBUGS . These are multivariate r and om effects models that allow for variation in true treatment effects across trials . We consider models where the between-trials variance is homogeneous across treatment comparisons as well as heterogeneous variance models . We also compare models with fixed ( unconstrained ) baseline study effects with models with r and om baselines drawn from a common distribution . These models are applied to an illustrative data set and posterior parameter distributions are compared . We discuss model critique and model selection , illustrating the role of Bayesian deviance analysis , and node-based model criticism . The assumptions underlying the MTC models and their parameterization are also discussed Abstract Objectives To assess the clinical effectiveness of surgical stabilisation ( spinal fusion ) compared with intensive rehabilitation for patients with chronic low back pain . Design Multicentre r and omised controlled trial . Setting 15 secondary care orthopaedic and rehabilitation centres across the United Kingdom . Participants 349 participants aged 18 - 55 with chronic low back pain of at least one year 's duration who were considered c and i date s for spinal fusion . Intervention Lumbar spine fusion or an intensive rehabilitation programme based on principles of cognitive behaviour therapy . Main outcome measure The primary outcomes were the Oswestry disability index and the shuttle walking test measured at baseline and two years after r and omisation . The SF-36 instrument was used as a secondary outcome measure . Results 176 participants were assigned to surgery and 173 to rehabilitation . 284 ( 81 % ) provided follow-up data at 24 months . The mean Oswestry disability index changed favourably from 46.5 ( SD 14.6 ) to 34.0 ( SD 21.1 ) in the surgery group and from 44.8 ( SD14.8 ) to 36.1 ( SD 20.6 ) in the rehabilitation group . The estimated mean difference between the groups was –4.1 ( 95 % confidence interval –8.1 to –0.1 , P = 0.045 ) in favour of surgery . No significant differences between the treatment groups were observed in the shuttle walking test or any of the other outcome measures . Conclusions Both groups reported reductions in disability during two years of follow-up , possibly unrelated to the interventions . The statistical difference between treatment groups in one of the two primary outcome measures was marginal and only just reached the predefined minimal clinical difference , and the potential risk and additional cost of surgery also need to be considered . No clear evidence emerged that primary spinal fusion surgery was any more beneficial than intensive rehabilitation Study Design . R and omized , controlled , multicenter , investigational device exemption trial . Objective . To investigate the safety and effectiveness of the first two-piece , metal-on-metal lumbar disc prosthesis for treating patients with single-level degenerative disc disease . Summary of Background Data . For patients with degenerative disc disease unresponsive to conservative measures , lumbar disc arthroplasty provides an alternative to fusion design ed to relieve persistent discogenic pain and maintain motion . Methods . After 2:1 r and omization , 577 patients were treated in either the investigational group ( 405 ) , receiving lumbar disc arthroplasty , or the control group ( 172 ) , receiving anterior lumbar interbody fusion . Patients were evaluated preoperatively , at surgery/discharge , and at 1.5 , 3 , 6 , 12 , and 24 months after surgery . The primary study endpoint was overall success , a composite measure of safety and effectiveness as recommended by the Food and Drug Administration and defined in the protocol . Results . Both treatment groups demonstrated significant improvements compared with preoperative status . The investigational group had statistically superior outcomes ( P < 0.05 ) at all postoperative evaluations in Oswestry Disability Index , back pain , and Short Form-36 Physical Component Summary scores as well as patient satisfaction . Investigational patients had longer surgical times ( P < 0.001 ) and greater blood loss ( P < 0.001 ) than did control patients ; however , hospitalization stays were similar for both groups . Investigational patients had fewer implant or implant/surgical procedure-related adverse events ( P < 0.001 ) . Return-to-work intervals were reduced for investigational patients . Disc height and segmental angular motion were maintained throughout the study in the investigational group . In the investigational group , overall success superiority was found when compared to the control group as defined by the Food and Drug Administration Investigational Device Exemption protocol . Conclusion . The investigational group consistently demonstrated statistical superiority versus fusion on key clinical outcomes including improved physical function , reduced pain , and earlier return to work Purpose To compare the 9-year outcome in patients with chronic low back pain treated by instrumented lumbar fusion versus cognitive intervention and exercises . Methods The main outcome measure was the Oswestry Disability Index ( ODI ) . Secondary outcome measures included pain , fear-avoidance beliefs , trunk muscle strength , medication , and return to work . Results One-third of the patients r and omized to cognitive intervention and exercises had crossed over and been operated and one-third of the patients allocated to lumbar fusion had been re-operated . The intention-to-treat analysis detected no differences between the two groups . The mean adjusted treatment effect for ODI was 1.9 ( 95 % CI −7.8 to 11.6 ) . Analysed according to the treatment received , more operated patients used pain medication and were out of work . Conclusions The outcome at 9 years was not different between instrumented lumbar fusion and cognitive intervention and exercises The study design includes a prospect i ve , r and omised controlled study comparing total disc replacement ( TDR ) with posterior fusion . The main objective of this study is to compare TDR with lumbar spinal fusion , in terms of clinical outcome , in patients referred to a spine clinic for surgical evaluation . Fusion is effective for treating chronic low back pain ( LBP ) , but has drawbacks , such as stiffness and possibly adjacent level degradation . Motion-preserving options have emerged , of which TDR is frequently used because of these drawbacks . How the results of TDR compare to fusion , however , is uncertain . One hundred and fifty-two patients with a mean age of 40 years ( 21–55 ) were included : 90 were women , and 80 underwent TDR . The patients had not responded to a conservative treatment programme and suffered from predominantly LBP , with varying degrees of leg pain . Diagnosis was based on clinical examination , radiographs , MRI , and in unclear cases , diagnostic injections . Outcome measures were global assessment ( GA ) , VAS for back and leg pain , Oswestry Disability Index , SF36 and EQ5D at 1 and 2 years . Follow-up rate was 100 % , at both 1 and 2 years . All outcome variables improved in both groups between preoperative and follow-up assessment . The primary outcome measure , GA , revealed that 30 % in the TDR group and 15 % in the fusion group were totally pain-free at 2 years ( P = 0.031 ) . TDR patients had reached maximum recovery in virtually all variables at 1 year , with significant differences compared to the fusion group . The fusion patients continued to improve and at 2 years had results similar to TDR patients apart from numbers of pain-free . Complications and reoperations were similar in both groups , but pedicle screw removal as additive surgery , was frequent in the fusion group . One year after surgery , TDR was superior to spinal fusion in clinical outcome , but this difference had diminished by 2 years , apart from ( VAS for back pain and ) numbers of pain-free . The long-term benefits have yet to be examined BACKGROUND Disc replacement arthroplasty previously has been shown to be an effective alternative to spine fusion for the treatment of single-level lumbar degenerative disc disease . The purpose of the present study was to determine the twenty-four-month results of a clinical trial of the ProDisc-L total disc replacement as compared with spinal fusion for the treatment of degenerative disc disease at two contiguous vertebral levels from L3 to S1 . METHODS A total of 237 patients were treated in a r and omized controlled trial design ed as a non-inferiority study for regulatory application purpose s. Blocked r and omization was performed with use of a 2:1 ratio of total disc arthroplasty to circumferential arthrodesis . Evaluations , including patient self- assessment s , physical and neurological examinations , and radiographic examinations , were performed preoperatively , six weeks postoperatively , and three , six , twelve , eighteen , and twenty-four months postoperatively . RESULTS At twenty-four months , 58.8 % ( eighty-seven ) of 148 patients in the total disc replacement group were classified as a statistical success , compared with 47.8 % ( thirty-two ) of sixty-seven patients in the arthrodesis group ; non-inferiority was demonstrated . The mean Oswestry Disability Index in both groups significantly improved from baseline ( p < 0.0001 ) ; the mean percentage improvement for the total disc replacement group was significantly better than that for the arthrodesis group ( p = 0.0282 ) . An established clinical criterion for success , a ≥15-point improvement in the Oswestry Disability Index from baseline , occurred in 73.2 % ( 109 ) of 149 patients in the total disc replacement group and 59.7 % ( thirty-seven ) of sixty-two patients in the arthrodesis group . The Short Form-36 physical component scores were significantly better for the total disc replacement group as compared with the arthrodesis group ( p = 0.0141 at twenty-four months ) . Visual analog scale scores for satisfaction significantly favored total disc replacement from three to twenty-four months . At twenty-four months , 78.2 % ( 111 ) of 142 patients in the total disc replacement group and 62.1 % ( thirty-six ) of fifty-eight patients in the arthrodesis group responded " yes " when asked if they would have the same surgery again . Lumbar spine range of motion on radiographs averaged 7.8 ° at the superior disc and 6.2 ° at the inferior disc in patients with total disc replacement . Reduction in narcotics usage significantly favored the total disc replacement group at twenty-four months after surgery ( p = 0.0020 ) . CONCLUSIONS Despite the relatively short duration of follow-up and design limitations , the present study suggests that two-level lumbar disc arthroplasty is an alternative to and offers clinical advantages in terms of pain relief and functional recovery in comparison with arthrodesis . Longer-term follow-up is needed to determine the risks for implant wear and /or degenerative segment changes Abstract The effectiveness of lumbar fusion for chronic low back pain after surgery for disc herniation has not been evaluated in a r and omized controlled trial . The aim of the present study was to compare the effectiveness of lumbar fusion with posterior transpedicular screws and cognitive intervention and exercises . Sixty patients aged 25–60 years with low back pain lasting longer than 1 year after previous surgery for disc herniation were r and omly allocated to the two treatment groups . Experienced back surgeons performed transpedicular fusion . Cognitive intervention consisted of a lecture intended to give the patient an underst and ing that ordinary physical activity would not harm the disc and a recommendation to use the back and bend it . This was reinforced by three daily physical exercise sessions for 3 weeks . The primary outcome measure was the Oswestry Disability Index ( ODI ) . Outcome data were analyzed on an intention‐to‐treat basis . Ninety‐seven percent of the patients , including seven of eight patients who had either not attended treatment ( n = 5 ) or changed groups ( n = 2 ) , completed 1‐year follow‐up . ODI was significantly improved from 47 to 38 after fusion and from 45 to 32 after cognitive intervention and exercises . The mean difference between treatments after adjustment for gender was −7.3 ( 95 % CI −17.3 to 2.7 , p = 0.15 ) . The success rate was 50 % in the fusion group and 48 % in the cognitive intervention/exercise group . For patients with chronic low back pain after previous surgery for disc herniation , lumbar fusion failed to show any benefit over cognitive intervention and exercises Study Design . Prospect i ve observational study . Objectives . To evaluate the role of work status as a predictor of outcome from anterior lumbar fusion . Summary of Background Data . Many psychosocial factors have been identified as predictors of chronic disability and of outcomes of surgery . Workers ' Compensation and job satisfaction are two of the strongest and most evaluated factors . Work status at the time of intervention may also be relevant but has rarely been studied independently in patients having lumbar fusion . Methods . A total of 106 patients with discogenic low back pain were treated by anterior lumbar interbody fusion . Patients were prospect ively monitored by VAS , Rol and Morris score , and work status . The influence of preoperative work status on outcome variables was assessed using odds ratios . A multivariate analysis was performed to assess influence of other confounding variables . Follow-up was a mean 29.7 months with 95 % greater than 1 year . Results . Patients working at the time of surgery had a 10.5 times greater likelihood of working at follow-up . Overall , only 43 % of nonworkers were working at follow-up compared with 90 % of patients who were working before surgery . This association was independent of Workers ' Compensation , number of levels treated , and other demographic variables . A greater degree of pain relief was seen in patients working before surgery but not in function as measured by the Rol and Morris score . Conclusion . These results show that patients with chronic low back pain should be encouraged to continue working up until surgery Study Design . A prospect i ve , r and omized , multicenter , Food and Drug Administration-regulated Investigational Device Exemption clinical trial . Objectives . The purpose of this study was to compare the safety and effectiveness of lumbar total disc replacement , using the CHARITÉ ™ artificial disc ( DePuy Spine , Raynham , MA ) , with anterior lumbar interbody fusion , for the treatment of single-level degenerative disc disease from L4-S1 unresponsive to nonoperative treatment . Summary of Background Data . Reported results of lumbar total disc replacement have been favorable , but studies have been limited to retrospective case series and /or small sample sizes . Methods . Three hundred four ( 304 ) patients were enrolled in the study at 14 centers across the United States and r and omized in a 2:1 ratio to treatment with the CHARITÉ ™ artificial disc or the control group , instrumented anterior lumbar interbody fusion . Data were collected pre- and perioperatively at 6 weeks and at 3 , 6 , 12 , and 24 months following surgery . The key clinical outcome measures were a Visual Analog Scale assessing back pain , the Oswestry Disability Index question naire , and the SF-36 Health Survey . Results . Patients in both groups improved significantly following surgery . Patients in the CHARITÉ ™ artificial disc group recovered faster than patients in the control group . Patients in the CHARITÉ ™ artificial discgroup had lower levels of disability at every time interval from 6 weeks to 24 months , compared with the control group , with statistically lower pain and disability scores at all but the 24 month follow-up ( P < 0.05 ) . At the 24-month follow-up period , a significantly greater percentage of patients in the CHARITÉ ™ artificial disc group expressed satisfaction with their treatment and would have the same treatment again , compared with the fusion group ( P < 0.05 ) . The hospital stay was significantly shorter in the CHARITÉ ™ artificial disc group ( P < 0.05 ) . The complication rate was similar between both groups . Conclusions . This prospect i ve , r and omized , multicenter study demonstrated that quantitative clinical outcome measures following lumbar total disc replacement with the CHARITÉ ™ artificial disc are at least equivalent to clinical outcomes with anterior lumbar interbody fusion . These results support earlier reports in the literature that total disc replacement with the CHARITÉ ™ artificial disc is a safe and effective alternative to fusion for the surgical treatment of symptomatic disc degeneration in properly indicated patients . The CHARITÉ ™ artificial disc group demonstrated statistically significant superiority in two major economic areas , a 1-day shorter hospitalization , and a lower rate of reoperations ( 5.4 % compared with 9.1 % ) . At 24 months , the investigational group had a significantly higher rate of satisfaction ( 73.7 % ) than the 53.1 % rate of satisfaction in the control group ( P = 0.0011 ) . This prospect i ve r and omized multicenter study also demonstrated an increase in employment of 9.1 % in the investigational group and 7.2 % in the control group BACKGROUND CONTEXT Given the unsustainable costs of the US health-care system , health-care purchasers , payers , and hospital systems are adopting the concept of value-based purchasing by shifting care away from low- quality providers or hospitals . Legislation now allows public reporting of these quality rankings . True measures of quality , such as surgical morbidity and vali date d question naires of effectiveness , are burdensome and costly to collect . Hence , patients ' satisfaction with care has emerged as a commonly used metric as a proxy for quality because of its feasibility of collection . However , patient satisfaction metrics have yet to be vali date d as a measure of overall quality of surgical spine care . PURPOSE We set out to determine whether patient satisfaction is a valid measure of safety and effectiveness of care in a prospect i ve longitudinal spine registry . STUDY DESIGN Prospect i ve longitudinal cohort study . PATIENT POPULATION All patients undergoing elective spine surgery for degenerative conditions over a 6-month period at a single medical center . OUTCOME MEASURES Patient-reported outcome instruments ( numeric rating scale [ NRS ] , Oswestry disability index [ ODI ] , neck disability index [ NDI ] , short-form 12-item survey [ SF-12 ] , Euro-Qol-5D [ EQ-5D ] , Zung depression scale , and Modified Somatic Perception Question naire [ MSPQ ] anxiety scale ) , return to work , patient satisfaction with outcome , and patient satisfaction with provider care . METHODS All patients undergoing elective spine surgery for degenerative conditions over a 6-month period at a single medical center were enrolled into a prospect i ve longitudinal registry . Data collected on all patients included demographics , disease characteristics , treatment variables , readmissions/reoperations , and all 90-day surgical morbidity . Patient-reported outcome instruments ( NRS , ODI , NDI , SF-12 , EQ-5D , Zung depression scale , and MSPQ anxiety scale ) , return to work , patient satisfaction with outcome , and patient satisfaction with provider care were recorded at baseline and 3 months after treatment . Receiver-operating characteristic ( ROC ) curve analysis was performed to determine whether extent of improvement in quality of life ( SF-12 physical component summary [ PCS ] ) and disability ( ODI/NDI ) accurately predicted patient satisfaction versus dissatisfaction . St and ard interpretation of area under the curve ( AUC ) was used : less than 0.7 , poor ; 0.7 to 0.8 , fair ; and greater than 0.8 , good accuracy . Multivariate logistic regression analysis was performed to determine if surgical morbidity ( quality ) or improvement in disability and quality of life ( effectiveness of care ) were independently associated with patient satisfaction . RESULTS Four hundred twenty-two ( 84 % ) patients completed all question naires 3 months after surgery during the review ed time period ( mean age 55±14 years ) . Lumbar surgery was performed in 287 ( 68 % ) and cervical surgery in 135 ( 32 % ) patients . There were 51 ( 12.1 % ) 90-day complications , including 21 ( 5.0 % ) readmissions and 12 ( 2.8 % ) return to operating room . Three hundred fifty-eight ( 84.8 % ) patients were satisfied with provider care and 288 ( 68.2 % ) with their outcome . Satisfaction with provider care : In ROC analyses , extent of improvement in quality of life ( SF-12 ) and disability ( ODI/NDI ) differentiated satisfaction versus dissatisfaction with care with very poor accuracy ( AUC 0.49 - 0.69 ) . In regression analysis , 3-month morbidity ( odds ratio [ 95 % confidence interval ] : 1.45 [ 0.79 - 2.66 ] ) , readmission ( 0.66 [ 0.24 - 1.80 ] ) , improvement in quality of life ( SF-12 PCS ) , or improvement in general health ( health transition index ) were not associated with satisfaction with care . Satisfaction with outcome : In ROC analyses , improvement in quality of life ( SF-12 ) and disability ( ODI/NDI ) failed to differentiate satisfaction with good accuracy ( AUC 0.76 ) . Neither 90-day morbidity ( 1.05 [ 0.46 - 2.34 ] ) nor 90-day readmission ( 0.27 [ 0.04 - 2.04 ] ) was associated with satisfaction with outcome in regression analysis . CONCLUSIONS Patient satisfaction is not a valid measure of overall quality or effectiveness of surgical spine care . Patient satisfaction metrics likely represent the patient 's subjective contentment with health-care service , a distinct aspect of care . Satisfaction metrics are important patient-centered measures of health-care service but should not be used as a proxy for overall quality , safety , or effectiveness of surgical spine care Objective To compare the efficacy of surgery with disc prosthesis versus non-surgical treatment for patients with chronic low back pain . Design A prospect i ve r and omised multicentre study . Setting Five university hospitals in Norway . Participants 173 patients with a history of low back pain for at least one year , Oswestry disability index of at least 30 points , and degenerative changes in one or two lower lumbar spine levels ( 86 patients r and omised to surgery ) . Patients were treated from April 2004 to September 2007 . Interventions Surgery with disc prosthesis or outpatient multidisciplinary rehabilitation for 12 - 15 days . Main outcome measures The primary outcome measure was the score on the Oswestry disability index after two years . Secondary outcome measures were low back pain , satisfaction with life ( SF-36 and EuroQol EQ-5D ) , Hopkins symptom check list ( HSCL-25 ) , fear avoidance beliefs ( FABQ ) , self efficacy beliefs for pain , work status , and patients ’ satisfaction and drug use . A blinded independent observer evaluated scores on the back performance scale and Prolo scale at two year follow-up . Results The study was powered to detect a difference of 10 points on the Oswestry disability index between the groups at two years . At two years there was a mean difference of −8.4 points ( 95 % confidence interval −13.2 to −3.6 ) in favour of surgery . In the analysis of prespecified secondary outcomes , there were significant differences in favour of surgery for low back pain ( mean difference −12.2 , −21.3 to −3.1 ) , patients ’ satisfaction ( 63 % ( n=46 ) v 39 % ( n=26 ) ) , SF-36 physical component score ( mean difference 5.8 , 2.5 to 9.1 ) , self efficacy for pain ( mean difference 1.0 , 0.2 to 1.9 ) , and the Prolo scale ( mean difference 0.9 , 0.1 to 1.6 ) . There were no significant differences in return to work , SF-36 mental component score , EQ-5D , fear avoidance beliefs , Hopkins symptom check list , drug use , and the back performance scale . One serious complication of leg amputation occurred during surgical revision of a polyethylene dislodgement . The drop-out rate was 20 % ( 34 ) and the crossover rate was 6 % ( 5 ) . Conclusions Surgical intervention with disc prosthesis for chronic low back pain result ed in a significantly greater improvement in the Oswestry score compared with rehabilitation , but this improvement did not clearly exceed the prespecified minimally important clinical difference between groups of 10 points , and the data are consistent with a wide range of differences between the groups , including values well below 10 points . The potential risks of surgery and the substantial amount of improvement experienced by a sizeable proportion of the rehabilitation group also have to be incorporated into overall decision making . Trial registration NCT 00394732 |
1,265 | 24,657,303 | The presence of CTCs and DTCs is associated with adverse clinicopathological characteristics and poor clinical outcomes in ovarian cancer patients . | OBJECTIVES Detecting circulating tumor cells ( CTCs ) in the peripheral blood and disseminated tumor cells ( DTCs ) in the bone marrow of cancer patients has proven feasible and of prognostic value in different neoplasms .
However , the clinical significance of CTCs and DTCs in ovarian cancer and its association with outcome remains unclear . | OBJECTIVE Serial circulating tumor cell ( CTC ) counts have demonstrated predictive and prognostic value in patients with metastatic breast , colorectal , and prostate cancer . In a phase III study of pegylated liposomal doxorubicin ( PLD ) with trabectedin vs. PLD for relapsed ovarian cancer , we evaluated the correlation , if any , between numbers of CTCs and progression free survival , ( PFS ) and overall survival ( OS ) . METHODS CTCs were isolated from peripheral blood ( 10 mL ) using the Cell Search system and reagents ( Veridex ) . A CTC is defined as EpCAM+ , cytokeratin+ , CD45- , and is positive for the nuclear stain DAPI . The normal reference range for Cell Search is < 2 CTC/7.5 mL of blood . Hazard ratios adjusted for known prognostic factors were estimated by Cox regression . RESULTS Two-hundred sixteen patients had baseline CTC measurements of which 111 ( 51.4 % ) were r and omized to the trabectedin+PLD arm ; 143/216 patients ( 66.2 % ) were platinum-sensitive . Thirty-one of 216 patients ( 14.4 % ) had 2 or more CTCs detected prior to the start of therapy ( range 2 - 566 ) . Univariate Cox regression analyses indicated that patients with ≥2 CTCs prior to therapy had 1.89- ( p=0.003 ) and 2.06-fold ( p=0.003 ) higher risk for progression and death respectively . Multivariate analyses that include baseline CA-125 , platinum sensitivity status , largest diameter lesion , number of tumor lesions , ECOG PS , and tumor grade show that patients with elevated baseline CTC had 1.58- ( p=0.058 ) and 1.54-fold ( p=0.096 ) higher risk for progression and death respectively . CONCLUSIONS Results from this study indicate that elevated numbers of CTCs impart an unfavorable prognosis for ovarian cancer patients OBJECTIVE Serum CA-125 values have been advocated in the monitoring of ovarian cancer patients receiving intravenous ( IV ) chemotherapy . This evaluation sought to determine if the CA-125 test can be used to monitor treatment effect among patients receiving intraperitoneal chemotherapy ( IP ) . METHODS Patient charts from a phase III clinical trial ( GOG 172 ) were retrospectively review ed . Serum CA-125 levels prior to each cycle of therapy were collected and compared between the IV and IP chemotherapy delivery . The association between CA-125 and progression-free survival ( PFS ) or overall survival ( OS ) was estimated and the homogeneity of the results between IP and IV chemotherapy was assessed . RESULTS A total of 177 patients were treated with IV chemotherapy and 165 patients with IP chemotherapy with CA-125 data available were included in this analysis . The observed difference was not statistically significant in median CA-125 levels between the IV and IP arms at any time point ( P>0.05 for all ) . Following surgery and adjuvant chemotherapy , patients with an abnormal CA-125 > 35 U/ml were 2.45 times more likely to have disease progression ( 95 % CI : 1.52 - 3.95 , P<0.001 ) and 2.78 times more likely to die of disease ( 95 % CI : 1.66 - 4.65 , P<0.001 ) , compared to those with a CA-125 < 35 U/ml . These results were consistent with IP and IV chemotherapy . CONCLUSION Serum CA-125 levels decrease in a similar manner during IP chemotherapy when compared to IV chemotherapy . Serum CA-125 algorithms for monitoring treatment effect that have been established for IV chemotherapy may also be applied for patients receiving IP chemotherapy OBJECTIVE Patients with persistent/recurrent epithelial ovarian cancer/ primary peritoneal cancer ( EOC/PPC ) have limited treatment options . AKT and PI3 K pathway activation is common in EOC/PPC , result ing in constitutive activation of downstream mTOR . The GOG conducted a phase II evaluation of efficacy and safety for the mTOR inhibitor , temsirolimus in EOC/PPC and explored circulating tumor cells ( CTC ) and AKT/mTOR/downstream tumor markers . METHODS Eligible women with measurable , persistent/recurrent EOC/PPC who had received 1 - 3 prior regimens were treated with 25 mg weekly IV temsirolimus until progression or intolerable toxicity . Primary endpoints were progression-free survival ( PFS ) ≥6-months , tumor response , and toxicity . Cell Search ® system was used to examine CTC , and AKT/mTOR/downstream markers were evaluated by archival tumor immunohistochemistry . Kendall 's tau-b correlation coefficient ( r ) and Cox regression modeling were used to explore marker associations with baseline characteristics and outcome . RESULTS Sixty patients were enrolled in a two-stage sequential design . Of 54 eligible and evaluable patients , 24.1 % ( 90 % CI 14.9%-38.6 % ) had PFS ≥6 months ( median 3.1 months ) , 9.3 % ( 90 % CI 3.7%-23.4 % ) experienced a partial response . Grade 3/4 adverse events included metabolic ( 8) , gastrointestinal ( 8) , pain ( 6 ) , constitutional ( 5 ) and pulmonary ( 4 ) . Suggested associations were between cyclin D1 and PFS ≥6 months , PFS or survival ; positive CTC pre-treatment and lack of response ; and high CTC expression of M30 and PFS ≥6 months/longer PFS . CONCLUSIONS Temsirolimus appears to have modest activity in persistent/recurrent EOC/PPC ; however , PFS is just below that required to warrant inclusion in phase III studies in unselected patients . Cyclin D1 as a selection marker and CTC measures merit further study BACKGROUND Our group evaluated the risk of recurrence for optimally treated advanced epithelial ovarian cancer ( adEOC ) in patients with a low-level rising serum CA-125 concentration within the normal range ( 0 - 35 kU/l ) . In addition , we tested the new proposed early CA-125 signal of progressive disease ( EPD ) criterion in the same study population . PATIENTS AND METHODS Patients treated from 1998 to 2006 for adEOC were identified at our institution . Inclusion criteria were as follows : CA-125 at time of diagnosis ( > 35 kU/l ) ; International Federation of Gynecology and Obstetrics stages III-IV treated with optimal primary treatment ; and complete response ( CR ) to primary treatment with normalization of CA-125 . RESULTS Median progression-free survival and overall survival for the recurrence group ( n = 60 ) were 17.7 and 38.2 months , respectively . The median follow-up time from CR to last contact was 40.2 months for patients in the nonrecurrence group ( n = 36 ) . An absolute increase in serum CA-125 levels of > or=5 kU/l compared with baseline CA-125 nadir values was significantly predictive of recurrence ( odds ratio for recurrence = 402.98 , P < 0.0001 ) . The progression date was pre date d by the EPD criterion in 77 % of patients with known progressive disease ( median , 58 days early ) with a sensitivity of 90 % , a positive predictive value of 96.4 % , and a false-positive rate of 5.6 % . CONCLUSIONS Among patients with optimally treated adEOC in complete remission , a low-level increase in serum CA-125 concentration within the normal range is a strong independent predictive factor for disease recurrence . In this patient population , future prospect i ve r and omized trials should consider the evaluation of the EPD criterion OBJECTIVE To determine whether circulating tumor cells ( CTCs ) , as detected and enumerated by the Veridex Cell Search system , could predict for clinical outcomes in women with newly diagnosed or recurrent epithelial ovarian cancer . METHODS Serial measurements of CTC s and paired serum CA125 were collected in a series of 78 women with newly diagnosed or recurrent ovarian cancer seen at our institution over a period of 15 months . Clinical data were abstract ed from patient medical records . CTCs were detected and enumerated by the Cell Search protocol , and patients were divided into CTC negative ( < 2 CTCs ) or positive ( ≥2 CTCs ) groups . CTC groups were correlated with clinical characteristics and outcomes . A longitudinal analysis of CTC change and CA125 trends was also performed . RESULTS At least one CTC was isolated from the peripheral blood of over 80 % of the women participating in this study , with a range from 0 to 8 . No correlations were observed between CTC numbers and clinical characteristics or outcomes . Although both serum CA125 and CTC number exhibited an overall significant decreasing trend over time , there was no correlation observed between change in CTCs and CA125 . CONCLUSION Using the FDA -approved Cell Search system , CTCs can be isolated from women with newly diagnosed or recurrent ovarian cancer . However , CTC numbers do not significantly correlate with clinical characteristics or patient outcomes . Future studies should focus on phenotypic characterization of CTCs and whether different isolation protocol s yield a higher number of CTCs or add prognostic value |
1,266 | 23,152,258 | Data for pooling individual outcomes were available for a maximum of nine trials and 54 % of participants .There were no statistically or clinical ly significant differences between double-bundle and single-bundle reconstruction in the subjective functional knee scores ( subjective IKDC score , Tegner activity score , Lysholm score ) in the intermediate ( six months up to two years since surgery ) or long term ( two to five years from surgery ) .
There is insufficient evidence to determine the relative effectiveness of double-bundle and single-bundle reconstruction for anterior cruciate ligament rupture in adults , although there is limited evidence that double-bundle ACL reconstruction has some superior results in objective measurements of knee stability and protection against repeat ACL rupture or a new meniscal injury . | BACKGROUND Arthroscopic reconstruction for anterior cruciate ligament rupture is a common orthopaedic procedure .
One area of controversy is whether the method of double-bundle reconstruction , which represents the ' more anatomical ' approach , gives improved outcomes compared with the more traditional single-bundle reconstruction .
OBJECTIVES To assess the effects of double-bundle versus single-bundle for anterior cruciate ligament reconstruction in adults with anterior cruciate ligament deficiency . | The aim of this study was to evaluate whether anterior cruciate ligament ( ACL ) reconstruction using the double bundle technique ( DB ) improves stability in the knee compared with the single bundle technique ( SB ) with the femoral tunnel in a more horizontal position ( 2 or 10 o’clock ) . We conducted a r and omized , prospect i ve study . Forty patients were r and omized to the DB group ( 20 patients ) and the SB group ( 20 patients ) . Four-str and ed semitendinosus and gracilis autologous grafts were used in the SB group and in the DB group the conventional four tunnel technique was carried out using the same tendons . The IKDC complete form was used for the preoperative evaluation , and in the follow-up the IKDC subjective knee evaluation form , IKDC current health assessment form and IKDC knee examination form were used . Anteroposterior ( AP ) laxity was evaluated by st and ardised and forced radiology in all patients . No significant preoperative between-group differences were found . During the follow-up , no differences were found between groups , except for significant between-group differences ( P < 0.05 ) between the preoperative and postoperative evaluations . The IKDC index also showed significant differences in the 2-year follow-up . Median scores increased from 48 ( range 41–54 ) to 81 ( range 75–87 ) ( P = 0.01 ) in the SB group and from 52 ( range 46–58 ) to 80 ( range 72–88 ) ( P = 0.02 ) in the DB group . There were no significant differences between the groups in terms of functional scores . In conclusion , the 2 and 10 o’clock placements showed no significant differences between SB and DB techniques in the pivot-shift test , manual and radiological anterior posterior laxity and IKDC scores . However , significant between-group differences were found between the preoperative and postoperative evaluations Twenty-six patients with anteroposterior ( AP ) laxity of the knee , associated with torn anterior cruciate ligament ( ACL ) , were prospect ively r and omized for arthroscopic lower femoral tunnel placed single- or double-bundle reconstruction using hamstring tendons . We evaluated AP and rotational stabilities under regular loads ( a 100-N anterior load and a 1.5-N m external – internal load ) before and after ACL reconstruction , comparing single- and double-bundle reconstruction with our original device for applying quantitative tibial rotation and the navigation system intraoperatively . No significant differences were found between the two groups in AP displacement and total range of tibial rotation at 30 ° and 60 ° of knee flexion . We found that a lower femoral tunnel placed single-bundle reconstruction reproduced AP and rotational stability as well as double-bundle reconstruction after reconstruction intraoperatively We conducted a prospect i ve r and omised study of anatomical single-bundle ( A-SB group ) versus double-bundle ( A-DB group ) anterior cruciate ligament ( ACL ) reconstruction using the hamstrings tendons . Twenty patients with unilateral ACL deficiency were r and omised into two groups . We created the bone tunnels at the position of the original insertion of the anteromedial bundle footprint and posterolateral bundle footprint in the A-DB group and at the central position between these two bundles in the A-SB group . All of the patients were tested before ACL reconstruction and one year after surgery . The KT-1000 measurements , isokinetic muscle peak torque and heel-height difference were evaluated and the general knee condition was assessed by Lysholm score . For pre- and postoperative stability assessment , we used the six-degrees-of-freedom of knee kinematic measurement system using an electromagnetic device ( the EMS ) for quantitative assessment during the Lachman test and the pivot shift test . There were no significant differences in the KT-1000 measurements , isokinetic muscle peak torque , heel-height difference , and Lysholm score at one-year follow-up between these two groups . The EMS data showed there were significant differences in the acceleration of the pivot shift test between the operated knee and the contralateral normal knees in the A-SB group . In conclusion , clinical outcomes were equally good in both groups . However , the EMS data showed the anatomical double-bundle ACL reconstruction tended to be biomechanically superior to the single-bundle reconstruction Purpose The purpose of this study was to compare subjective , objective and radiographic outcome of the lateralized single-bundle bone-patellar tendon-bone autograft with a non-anatomical double-bundle hamstring tendons autograft anterior cruciate ligament ( ACL ) reconstruction technique at long-term follow-up . Methods Seventy-nine non-consecutive r and omized patients ( 42 men ; 37 women ) with unilateral ACL insufficiency were prospect ively evaluated , before and after ACL reconstruction by means of the above-mentioned techniques , with a minimum follow-up of 8 years ( range 8–10 years ; mean 8.6 years ) . In the double-bundle hamstrings technique , we used one tibial and one femoral tunnel combined with one “ over-the-top ” passage , cortical staple ’s fixation and we left intact hamstrings ’ tibial insertion . Patients were evaluated subjectively and objective ly , using IKDC score , Tegner level , manual maximum displacement test with KT-2000 ™ arthrometer . Radiographic evaluation was performed according to IKDC grading system , and re-intervention rate for meniscal lesions was also recorded . Results The subjective and objective IKDC were similar in both groups while double-bundle hamstrings group showed significantly higher Tegner level ( P = 0.0007 ) , higher passive range of motion recovery ( P = 0.0014 ) , faster sport resumption ( P = 0.0052 ) , lower glide pivot-shift phenomenon ( P = 0.0302 ) and lower re-intervention rate ( P = 0.0116 ) compared with patellar tendon group . Radiographic evaluation showed significant lower objective degenerative changes in double-bundle hamstrings group at final follow-up ( P = 0.0056 ) . Conclusion Although both techniques provide satisfactory results , double-bundle ACL reconstruction shows better functional results , with a faster return to sport activity , a lower re-operation rate and lower degenerative knee changes 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 A total of 108 patients with unilateral instability of the knee , associated with rupture of the anterior cruciate ligament , was prospect ively r and omised for arthroscopic single- or double-bundle reconstruction of the ligament using hamstring tendons . The same post-operative rehabilitation protocol was used for all . The patients were followed up for a mean of 32 months ( 24 to 36 ) . We measured the anterior laxity and joint position sense at different angles of flexion of the knee to determine whether both bundles in the double-bundle reconstruction contributed to the stability of the joint and proprioception . No significant difference was found between the two groups with regard to anterior laxity measured by the KT-2000 arthrometer with the knee at 20 degrees or 70 degrees flexion nor with regard to proprioception . A notchplasty was required less often in the double- compared with the single-bundle reconstruction . We did not find any advantage in a double-bundle as opposed to a single-bundle reconstruction in terms of stability or proprioception Double-bundle anterior cruciate ligament ( ACL ) reconstruction is intended to replicate the anatomy and the function of the anteromedial and posterolateral bundles of the native ACL to improve patients ' satisfaction and knee stability . We prospect ively assigned 75 consecutive patients with an isolated ACL lesion to one of three sequential groups of 25 patients each . Group I received a single-bundle , single-incision transtibial ACL reconstruction . Groups II and III received a double-bundle reconstruction with a single-incision transtibial technique or a double-bundle , twoincision outside-in technique , respectively . We obtained subjective International Knee Documentation Committee and Knee Injury and Osteoarthritis Outcome Score evaluations and objective International Knee Documentation Committee scores and KT-1000 measurements preoperatively and at followup . All patients reached a minimum followup of 2 years . KT side-to-side difference in Groups I , II , and III were 2.4 , 1.6 and 1.4 mm , respectively . Group III had fewer patients with a positive pivot shift than Group I. The double-bundle double-incision outside-in ACL reconstruction result ed in improved anteroposterior stability and less residual pivot shift than single-incision single-bundle technique . Level of Evidence : Level II , therapeutic study . See Guidelines for Authors for a complete description of levels of evidence Several investigators have reported the presence of biomechanical , kinematic , anatomic , fiber orientation patterns and biological differences between the anteromedial bundle and the posterolateral bundle of ACL . The purpose of this prospect i ve r and omized study was to compare the clinical , instrumental and X-ray outcome of two ACL reconstruction techniques with hamstring tendons : one with a single intra-articular bundle associated to an extra-articular sling , the second with a more anatomic double-bundle technique that reproduces better the native ACL function . From an initial group of 100 patients who underwent ACL reconstruction , 72 patients ( 35 single bundle plus lateral plasty and 37 double bundle ) were evaluated with IKDC , Tegner score , KT2000 arthrometer , Activity Rating Scale , Psychovitality Question naire and Ahlback radiographic score at a mean 3 years follow-up . Double-bundle group showed significantly better results regarding IKDC , ROM , Activity Rating Scale and time to return to sport . Also KT 2000 showed significant differences in objective stability . The double-bundle technique for ACL reconstruction described in this paper has demonstrated significantly better subjective , objective and functional results compared with a double-str and ed hamstrings plus extra-articular sling at a minimum 3-year follow-up Double-bundle anterior cruciate ligament ( ACL ) reconstruction reproduces anteromedial and posterolateral bundles , and thus has theoretical advantages over conventional single-bundle reconstruction in controlling rotational torque in vitro . However , its superiority in clinical practice has not been proven . We analyzed rotational stability with three reconstruction techniques in 60 consecutive patients who were r and omly divided into three groups ( double-bundle , anteromedial single-bundle , posterolateral single-bundle ) . In the reconstructive procedure , the hamstring tendon was harvested and used as a free tendon graft . Followup examinations were performed 1 year after surgery . Anteroposterior laxity of the knee was examined with a KT-1000 arthrometer , whereas rotatory instability , as elicited by the pivot shift test , was assessed using a new measurement system incorporating three-dimensional electromagnetic sensors . Routine clinical evaluations , including KT examination , demonstrated no differences among the three groups . However , using the new measurement system , patients with double-bundle ACL reconstruction showed better pivot shift control of complex instability than patients with anteromedial and posterolateral single-bundle reconstruction . Level of Evidence : Level II , therapeutic study . See the Guideline for Authors for a complete description of levels of evidence Anatomical observation and biomechanical studies have shown that the anterior cruciate ligament ( ACL ) mainly consists of two distinct bundles , the anteromedial ( AM ) bundle and posterolateral ( PL ) bundle . Conventional single-bundle ACL reconstruction techniques have focused on the restoration of the AM bundle while giving limited attention to the PL bundle . The purpose of this prospect i ve , r and omized clinical study is to compare the outcomes of ACL reconstruction when using either double-bundle or single-bundle technique and bioabsorbable interference screw fixation , and similar rehabilitation with both techniques . Sixty-five patients were r and omized into either double-bundle ( n = 35 ) or single-bundle ( n = 30 ) ACL reconstruction with hamstring tendons and bioabsorbable screw ( Hexalon , Inion Company , Tampere , Finl and ) fixation in both groups . The evaluation methods were clinical examination , KT-1000 arthrometer measurements , radiographic evaluation , as well as International Knee Documentation Committee and Lysholm knee scores . There were no differences between the study groups preoperatively . For an average of 14 months of follow-up ( range 12–20 months ) , 30 patients of the double-bundle group and 29 patients of the single-bundle group were available ( 91 % ) . At the follow-up , the rotational stability , as evaluated by pivot shift test , was significantly better in the double-bundle group than in the single-bundle group . However , in anterior stability of the knee , there was no significant difference between the groups . None of the patients in the double-bundle group had graft failure , while four patients in the single-bundle group had . In addition , knee scores were equal at the follow-up , and all the results were significantly better at the follow-up than preoperatively , in both groups PURPOSE The purpose of this study was to obtain more than 2 years ' follow-up after surgery to investigate the effect of the difference in rotatory stability based on our previous data on the clinical outcome among 3 groups : double-bundle ( DB ) reconstruction group , anteromedial ( AM ) single-bundle reconstruction group , and posterolateral ( PL ) single-bundle reconstruction group . METHODS We r and omly separated 55 patients with anterior cruciate ligament rupture into 3 groups : 18 in DB group , 18 in AM group , and 19 in PL group . The mean follow-up period is 33.7 months for the DB group , 31.9 months for the AM group , and 33.2 months for the PL group . We evaluated the Lysholm score , Tegner score , anterior laxity with the KT-1000 arthrometer ( MEDmetric , San Diego , CA ) , rotator instability with the pivot-shift test , and muscle strength with knee extensor and flexor isokinetic peak torques at 60 ° /s . RESULTS There were no significant differences in postoperative Lysholm score and Tegner score . Anterior stability of the knee , as measured by the KT-1000 arthrometer , was significantly better in the DB group than the PL group ( P < .05 ) . The negative rate of the manual pivot-shift test in the DB group was significantly superior to the PL group ( P < .05 ) . Muscle strength of the extensor in the DB group was significantly superior to that in the AM group ( P < .05 ) , and muscle strength of the flexor in the PL group was significantly inferior to that in both the DB and AM groups ( P < .05 ) . Two patients in the PL group had rerupture ; however , there was no graft failure in the other groups . CONCLUSIONS At 2 years ' follow-up , patients undergoing DB anterior cruciate ligament reconstruction had greater extension strength than patients receiving an AM single-bundle reconstruction . The DB and AM groups had greater flexion strength than the PL group . The DB and AM groups had a similar rate of negative pivot-shift test results , whereas the PL group had fewer negative pivot-shift test results than the DB group . There were no KT-1000 side-to-side differences between the DB and AM groups , whereas the DB group had better results than the PL group . Overall , the clinical outcome as measured by Lysholm and Tegner scores was not different between groups . LEVEL OF EVIDENCE Level II , prospect i ve comparative study Background Double-bundle ACL reconstruction popularity is increasing with the aim to reproduce native ACL anatomy and improve ACL reconstruction outcome . However , to date , only a few r and omized clinical studies have been published . Purpose The aim of this study was to prospect ively compare the clinical results of single- and double-bundle ACL reconstruction . Study Design R and omized controlled clinical trial ; Level of evidence , 1 . Methods Seventy patients with a chronic unilateral ACL rupture who underwent arthroscopically assisted ACL reconstruction using a hamstring graft were r and omized to receive a single- ( SB ) or double-bundle ( DB ) reconstruction . Both groups were comparable with regard to preoperative data . A double-incision surgical technique was adopted in both groups . The graft was fixed by looping the hamstring tendons around a bony ( DB ) or a metallic ( SB ) bridge on the tibial side and with interference screws reinforced with a staple on the femur . The same rehabilitation protocol was adopted . Outcome assessment was performed by a blinded , independent observer using the visual analog scale ( VAS ) score , the new International Knee Documentation Committee ( IKDC ) form , the Knee Injury and Osteoarthritis Outcome Score ( KOOS ) , and KT-1000 arthrometer evaluation . Results All the patients reached a minimum follow-up of 2 years . No differences between the 2 groups were observed in terms of KOOS and IKDC subjective score . A statistically significant difference in favor of the DB group was found with the VAS ( P < .03 ) . The objective IKDC final scores showed statistically significantly more “ normal knees ” in the DB group than in the SB group ( P = .03 ) . There was 1 stability failure in the DB group and 3 in the SB group . The KT-1000 arthrometer data showed a statistically significant decrease in the average anterior tibial translation in the DB group ( 1.2 mm DB vs 2.1 mm SB ; P < .03 ) . The incidence of a residual pivot-shift glide was 14 % in DB and 26 % in SB ( P = .08 ) . Conclusion In the 2-year minimum follow-up , DB ACL reconstructions showed better VAS , anterior knee laxity , and final objective IKDC scores than SB . However , longer follow-up and accurate instrumented in vivo rotational stability assessment are needed PURPOSE The purpose of this study was to compare the clinical results of arthroscopic single-bundle and double-bundle anterior cruciate ligament ( ACL ) reconstruction . METHODS We design ed a prospect i ve study that included patients with an isolated ACL injury . From April 2004 to February 2007 , of 147 patients who underwent ACL reconstruction , 113 were included in this study . We serially obtained clinical and radiologic data preoperatively and postoperatively . We compared preoperative data and data at 2 years postoperatively in patients who had undergone single-bundle ACL reconstruction versus patients who had undergone double-bundle ACL reconstruction . There were 50 single-bundle reconstructions and 63 double-bundle reconstructions . Anteroposterior stability was assessed objective ly by anterior stress radiographs with the telos device ( telos , Marburg , Germany ) and the maximal manual test with the KT-2000 arthrometer ( MEDmetric , San Diego , CA ) . Rotational stability was determined by lateral pivot-shift test . The clinical results were assessed by International Knee Documentation Committee and Orthopadische Arbeitsgruppe Knie scores and Tegner activity scale . In addition , we evaluated postoperative thigh circumference and range of motion . RESULTS Residual anteroposterior laxity determined at 2 years postoperatively by telos and KT-2000 was 1.74 mm + /- 1.67 mm and 1.79 mm + /- 1.56 mm , respectively , in the single-bundle reconstruction group and 1.63 mm + /- 1.50 mm and 1.61 mm + /- 1.22 mm , respectively , in the double-bundle reconstruction group . There were no statistically significant differences . For the lateral pivot-shift test done at 2 years postoperatively , there was no statistically significant difference . In addition , clinical results such as International Knee Documentation Committee score , Orthopadische Arbeitsgruppe Knie score , Tegner activity scale , thigh circumference , and range of motion showed no significant differences between the 2 groups . CONCLUSIONS Double-bundle reconstruction of the ACL by a method using 2 femoral tunnel and 2 tibial tunnels showed no differences in stability results or any other clinical aspects or in terms of patient satisfaction . LEVEL OF EVIDENCE Level II , prospect i ve comparative study Anterior cruciate ligament ( ACL ) reconstruction in double-bundle technique is advocated to more closely restore the anatomy and function of the native ligament than conventional single-bundle technique . But up to now there are only a few clinical investigations comparing both techniques in a prospect i ve manner . We hypothesized that double-bundle ACL reconstruction reveals superior clinical and subjective results compared to single-bundle technique in a high-dem and collective . A total of 50 male patients ( mean age 29.4 years ) were prospect ively r and omized consecutively into one of the two reconstruction techniques . Group 1 ( SB ) underwent a 4-str and ed single-bundle reconstruction with a ST graft in femoral position at 10:00 and 02:00 o’clock , respectively . In group 2 ( DB ) , reconstruction was performed by using a 2-str and ed ST graft with double-bundle , four tunnel technique . Before surgery and at a 2 year follow-up ( range 23–25 months ) patients were evaluated by the same blinded observer . There was no significant difference in the side-to-side anterior laxity-measurement with the KT-1000 between both groups . As evaluated by the pivot shift , no significant correlation could be noted ( Fisher exact test P = 0.098 ) between rotational stability and any of the both reconstruction techniques . However , the anterior and rotational stability improved significantly at 2-year follow-up compared to preoperatively ( P = 0.003 ) in both groups . The statistical analysis showed a significant increase for the IKDC ( subjective , objective ) and the Lysholm Score at final follow-up among each single technique , while we found no significant difference between the two reconstruction methods . On the basis of our investigation , we conclude that reconstruction of the ACL by a double-bundle ST graft with an extracortical anchorage can achieve excellent clinical results . But in contrast to our initial hypothesis , we could not quote any significant advantages by creating two independent bundles . Reconstruction of the anterior cruciate ligament in conventional single-bundle technique with a more horizontal femoral tunnel placement obtains comparable clinical results in the present high-dem and collective The single-bundle ACL reconstruction ensures good outcomes and it is a well-established and widespread technique . Nevertheless , some patients still present residual pain and instability . Recent studies have showed that the double-bundle technique restores better natural ACL-fitting kinematics . Long-term clinical studies comparing the two surgical techniques are not frequent and there is no instrument to evaluate function and kinematics during the knee rotation in vivo . In this r and omised prospect i ve study performed on sportive people , we compare the BPTB single-bundle ACL reconstruction technique , which is the most common surgical technique performed on these patients ' category , with the ACL double-bundle reconstruction technique ( DB ) , in order to evaluate possible differences between the groups . Comparing the two groups , no statistically significant difference regarding the post-operative Lysholm score ( p=0.368 ) the Tegner activity scale ( p=0.519 ) and the arthrometric evaluation with KT-1000 ( p=0.74 ) have been observed . On the contrary , the IKDC evaluation showed a statistically significant difference ( p=0.004 ) better results of the DB group . Moreover , as assessed by the Tegner activity scale , only patients of the DB group were able to return to sports at a pre-injury level . Our data suggest that the double bundle ST/G ACL reconstruction technique results into slightly better outcome than the traditional technique of single-bundle BPTB . The verification and quantification of the advantages of this technique is anticipated with future studies focusing to the accurate measurement of knee rotation during different activities Background Several trials have been conducted to compare the clinical results between anatomic double-bundle and single-bundle anterior cruciate ligament ( ACL ) reconstruction procedures . In these studies , however , the number of patients was insufficient to compare the clinical results of the 2 procedures . Hypothesis The anatomic double-bundle procedure may be significantly better concerning the anterior laxity and the pivot-shift test than the single-bundle procedure , while there may be no significant differences in the other clinical evaluations and the intraoperative and postoperative complications between the 2 procedures . Study Design Cohort study ; Level of evidence , 2 . Methods Three hundred and twenty-eight patients with unilateral ACL reconstruction using hamstring autografts were divided into 2 groups . The first 157 consecutive patients underwent single-bundle reconstruction and the remaining 171 patients underwent anatomic double-bundle reconstruction . Concerning all background factors , there were no statistical differences between the 2 groups . Each patient was examined 2 years after surgery . Results No serious complications were experienced in either group . The anterior laxity was significantly less in the double-bundle reconstruction ( mean , 1.2 mm ) than in the single-bundle reconstruction ( mean , 2.5 mm ) . In the pivot-shift test , the double bundle ( + indication 16 % ; + + , 3 % ) was significantly better than the single bundle ( + result , 37 % ; + + , 12 % ) . The mean Lysholm score averaged 96.5 points ’ and 97.3 points in single-bundle and double-bundle reconstructions , respectively , while the International Knee Documentation Committee evaluation showed that 90 and 110 patients , respectively , were evaluated as rank A ( no significant difference between groups ) . There were no significant differences in the other clinical evaluations and the complications between the 2 procedures . Conclusions The postoperative anterior and rotational stability after the anatomic double-bundle ACL reconstruction was significantly better than that after the single-bundle reconstruction , although there were no significant differences between the 2 Procedures concerning the complications and the clinical evaluations PURPOSE The aim of this study was to compare tunnel enlargement in patients with double-bundle and single-bundle anterior cruciate ligament ( ACL ) reconstruction . METHODS Sixty patients were r and omized by closed envelopes into 2 different groups of ACL reconstruction with hamstring tendons : double-bundle technique with bioabsorbable screw fixation ( n = 35 ) and single-bundle technique with bioabsorbable screw fixation ( n = 25 ) . Magnetic resonance imaging evaluation was performed in 53 patients ( 88 % ) ( 32 in double-bundle group and 21 in single-bundle group ) for a mean of 27 months ' follow-up ( range , 24 to 36 months ) . Tunnel enlargement was determined by digital measurement of the widths perpendicular to the long axis of the tunnels on an oblique coronal and sagittal plane . The magnetic resonance imaging measurements were compared with the intraoperative drill diameter . RESULTS No significant differences were found between the double-bundle group and the single-bundle group in tunnel enlargement on the femoral side . However , on the tibial side , tunnel enlargement was greater in the single-bundle group than in the double-bundle group in each tunnel ( P = .051 ) . In all knees , tunnel enlargement both on the tibial side and on the femoral side correlated significantly with the anterior and rotational laxity of the operated knee . In the double-bundle group , no tunnel communication between the anteromedial and posterolateral tunnels was seen in any of the patients on either the tibial side or femoral side . CONCLUSIONS This prospect i ve , r and omized study showed that our double-bundle ACL reconstruction technique results in less tunnel enlargement in each tunnel on the tibial side than the single-bundle technique with similar fixation methods , graft material , and rehabilitation . In addition , no tunnel communication was observed in the patients undergoing double-bundle ACL reconstruction . The clinical results were good in both groups . However , the patients who had more tunnel enlargement had significantly more anterior and rotational laxity of the operated knee as well . LEVEL OF EVIDENCE Level I , therapeutic r and omized controlled trial Anatomical and biomechanical studies have shown that the anterior cruciate ligament ( ACL ) consists of two distinct bundles , the anteromedial ( AM ) and posterolateral . Each bundle has its specific role during the motion of the knee . ACL reconstruction techniques have focused on the restauration of the anteroposterior stability by substituting the more isometric AM bundle . Although these ligamentoplasties provide overall good results , in the last ten years double-bundle ACL reconstruction techniques have been developed , to better replicate the ligament anatomy . Despite the growing number of published studies , including r and omized controlled trials comparing single bundle and double bundle reconstructions , there is still a lack of evidence of any superiority of the double-bundle technique . Furthermore , many series are criticized for their poor assessement of rotational stability , using most of the time subjective pivot shift clinical testing . Among the methods available to measure tibial rotation , 3-D optoelectronic evaluation is an attractive tool and has been used in some studies reporting rotational mesurements after ACL single-bundle reconstruction . Our Department of Orthopaedics and Traumatology has been using double-bundle techniques for a few years . We conducted a preliminary prospect i ve r and omized study , in order to compare single and double-bundle techniques by clinical and optoelectronic evaluations Background Conventional anterior cruciate ligament reconstruction techniques have focused on restoration of the anterome-dial bundle only , which , however , may be insufficient in restoring the rotational stability of the knee . Hypothesis Rotational stability of the knee is better when using a double-bundle technique instead of a single-bundle technique for anterior cruciate ligament reconstruction . Study Design R and omized controlled clinical trial ; Level of evidence , 1 . Methods Seventy-seven patients were r and omized into 3 different groups for anterior cruciate ligament reconstruction with hamstring tendons : double-bundle with bioabsorbable screw fixation ( n = 25 ) , single-bundle with bioabsorbable screw fixation ( n = 27 ) , and single-bundle with metallic screw fixation ( n = 25 ) . The evaluation methods were clinical examination , KT-1000 arthrometric measurement , and the International Knee Documentation Committee and Lysholm knee scores . Results There were no differences between the study groups preoperatively . Seventy-three patients ( 95 % ) were available at a minimum 2-year follow-up ( range , 24–35 mo ) . The rotational stability of the knee , as evaluated by the pivot-shift test , was the best in the patients in the double-bundle group . In addition , the patients in the single-bundle groups had more graft failures than those in the double-bundle group . Concerning the anterior stability of the knee as measured with the KT-1000 arthrometer , the group differences were not statistically significant . No significant differences were found between the groups in knee scores . Conclusion Rotational stability of the knee is better when using the double-bundle technique instead of the single-bundle technique in anterior cruciate ligament reconstruction PURPOSE Biomechanical studies show increased anterior and rotational stability with double-bundle ( DB ) compared to single-bundle ( SB ) anterior cruciate ligament ( ACL ) reconstruction . The aim of this study was to evaluate the clinical results of four-tunnel DB ACL reconstruction . METHODS Seventy patients undergoing arthroscopic hamstring ACL reconstruction were prospect ively r and omized to DB ( n = 35 ) or SB ( n = 35 ) groups . Each bundle fixation was by means of a femoral EndoButton CL and a tibial biodegradable interference screw . Demographic data were comparable between groups , and the average age of all patients was 29 years . The average follow-up was 19 months for both groups and included a history , clinical evaluation with knee scores , and radiographs . RESULTS The subjective results were similar in groups . The subjective International Knee Documentation Committee ( IKDC ) 2000 score was 88 P for DB versus 90 P for SB ; the Lysholm score was 90 P for DB versus 93 P for SB ; and the Cincinnati knee score was 91 P for DB versus 92 P for SB . The objective IKDC was significantly higher for DB : 78 % " A " ( P < .000 ) and 19 % " B " compared to 24 % " A " and 68 % " B " for SB . The average KT-1000 side-to-side difference was 1.0 mm for DB and 1.6 mm for SB ( P = .054 ) and the pivot shift test was negative in 97 % for DB ( P = .01 ) and 71 % for SB . The range of motion was comparable for both groups . CONCLUSIONS Our study shows a significant advantage in anterior and rotational stability as well as objective IKDC for four-tunnel DB ACL reconstruction compared to SB ACL reconstruction . The subjective Cincinnati knee score , the Lysholm score , and the subjective IKDC 2000 did not show any statistical difference for one or the other technique . LEVEL OF EVIDENCE Level I , r and omized controlled trial PURPOSE To compare the clinical outcome of anatomic double-bundle anterior cruciate ligament ( ACL ) reconstruction with that of nonanatomic single- and double-bundle reconstructions . TYPE OF STUDY Prospect i ve comparative cohort study . METHODS Seventy-two patients with unilateral ACL-deficient knees were r and omly divided into 3 groups . Concerning all background factors , there were no statistical differences among the 3 groups . In group S ( n = 24 ) , single-bundle ACL reconstruction was performed . In group N-AD ( n = 24 ) , nonanatomic double-bundle reconstruction was carried out . In group AD ( n = 24 ) , anatomic double-bundle reconstruction was performed . One surgeon performed all operations using hamstring tendon autografts . Each patient underwent clinical examinations , before surgery and at 2 years . RESULTS No intraoperative and postoperative complications were experienced in each group . There were no significant differences concerning the time for operation among the 3 groups . The statistical analysis showed a significant difference in the postoperative side-to-side anterior laxity among the 3 groups ( P = .006 ) . The laxity was significantly less ( P = .002 ) in group AD ( 1.1 mm ) than in group S ( 2.8 mm ) , while there was no significant difference ( P = .072 ) between groups AD and N-AD . Concerning the pivot-shift test , group AD was significantly superior to group S ( P = .025 ) . There were no significant differences in the range of knee motion , the muscle torque , and the International Knee Documentation Committee evaluation . CONCLUSIONS On the basis of the KT-2000 measurement , the side-to-side anterior laxity of our anatomic double-bundle ACL reconstruction was significantly better than that of the single-bundle reconstruction with the hamstring tendon graft , although there were no significant differences in the other clinical measures among any of the 3 procedures . LEVEL OF EVIDENCE Level II Anatomic reconstructions of anterior cruciate ligament ( ACL ) with double bundle gracilis and semitendonosus tendons graft , reproducing AM and PL bundles , have been introduced to offer a better biomechanical outcome , especially during rotatory loads . On the other h and , many methods of tenodesing the lateral aspect of the tibia to the femur to reduce internal rotation ( IR ) of the tibia and minimize anterior translation of the tibia relative to the femur as a backup for intra-articular reconstruction , have been also suggested . The goal of this study is to evaluate the effect , on the IR of the tibia , of a lateral reconstruction in addition to a st and ard single bundle ACL reconstruction as compared with an anatomic double bundle ACL reconstruction . Computer assisted ACL reconstruction has been used because it could be very effective in evaluating the global kinematic performance of the reconstructed knee . We selected 20 consecutive ACL reconstruction procedures to be performed in males in our hospital . Patients were alternately assigned to one of the two groups––group A : st and ard single bundle ACL reconstruction with doubled gracilis and semitendinosus tendons graft with an arthroscopically assisted two incisions technique and a lateral extraarticular reconstruction ; group B : double bundle ACL reconstruction with doubled gracilis and semitendinosus tendons graft with an arthroscopically assisted two incisions technique . In all ACL reconstruction procedures navigation process was performed . Both surgical techniques reduced significantly AP displacement , IR and external rotation ( ER ) of the tibia respect to pre-operative ACL deficient condition ( p < 0.05 ) . Comparing the group A after the single bundle reconstruction and the group B after the AM bundle fixation , non differences were found in AP displacement , IR and ER of the tibia ( p = 0.75 , p = 0.07 and p = 0.07 respectively ; power : 0.94 ) . Comparing the group A after the addition of the lateral tenodesis and group B after the PL bundle fixation ( AM + PL ) no differences in AP tibial displacement and in ER of tibia were found ( p = 0.9 and 0.15 , respectively ; power : 0.99 ) ; however a significant reduction in IR of the tibia was found in group A after the addition of the lateral tenodesis respect to the group B after the addition of the PL bundle ( p = 0.0001 ; power : 0.26 ) . On the basis of our study , the addition of a lateral extraarticular reconstruction to a st and ard single bundle ACL reconstruction with hamstrings tendons graft in an “ in vivo ” reconstruction , is more effective in reducing the IR of the tibia at 30 ° of knee flexion , as compared with a st and ard single bundle ACL reconstruction and with an anatomic double bundle reconstruction is confirmed A total of 218 patients with unilateral anterior cruciate ligament deficiency were r and omly assigned to one of four groups . In group A an anatomical double bundle anterior cruciate ligament reconstruction was performed ; group B were treated by a single bundle using an Endobutton for femoral fixation ; in group C by a single bundle using RigidFix cross pins for femoral fixation ; and in group D by a single bundle using a bioabsorbable TransFix II screw for femoral fixation . For tibial fixation a bioabsorbable Intrafix interference screw was used for all the groups and the graft was fashioned from the semitendinosus and gracilis tendons in all patients . In all , 18 patients were lost to follow-up . The remaining 200 were subjected to a clinical evaluation , with assessment of the anterior drawer , Lachman 's and the pivot-shift tests , and KT-1000 arthrometer measurement . They also completed the International Knee Documentation Committee , Lysholm knee and Tegner activity scores . At a mean of 29 months ( 25 to 38 ) follow-up there were no significant differences concerning time between injury and range of movement and Lysholm knee scores among the four groups . However , the double bundle method showed significantly better results for the pivot-shift test ( p = 0.002 ) . The KT 1000 measurements showed a mean difference between the reconstructed knee and the patients ' normal knee of 1.4 mm in the double bundle group and 2.4 mm in the single bundle group ; which was statistically significant . The Lachman and anterior drawer tests also showed superior results for the double bundle method . The International Knee Documentation Committee scale showed no significant difference among the groups ( p < 0.001 ) . On clinical evaluation the double bundle group showed less laxity than the single bundle groups . However , regardless of the technique , all knees were improved by anterior cruciate ligament reconstruction compared with their pre-operative status Background : Controversy persists as to whether double-bundle reconstruction of the anterior cruciate ligament ( ACL ) has any clinical advantage over single-bundle reconstruction . Several studies have used subjective and nonquantitative manual tests to evaluate the rotatory stability of the knee . The authors have developed a method to quantitate the rotatory stability of the ACL-deficient knee using open magnetic resonance imaging ( MRI ) . Hypothesis : Anatomic double-bundle reconstruction restores rotatory stability significantly better than does single-bundle reconstruction . Study Design : Cohort study ; Level of evidence , 3 . Methods : Twenty-three consecutive patients treated with the single-bundle reconstruction ( group S ) and 25 consecutive patients treated with the anatomic double-bundle reconstruction ( group D ) were evaluated . Both reconstruction procedures were performed using hamstring tendon autografts . The Slocum anterolateral rotatory instability ( ALRI ) test was performed 1 year after surgery using open MRI . To assess rotatory stability , we measured the difference in anterior tibial translation between medial and lateral compartments in the sagittal plane and defined this difference as the ALRI value . In addition , clinical examinations consisting of the Lysholm knee score , Tegner activity score , KT-2000 arthrometer anterior translation examination , and the pivot-shift test were carried out . Results : The mean side-to-side difference in ALRI values was significantly less ( P < .001 ) in double-bundle reconstruction ( mean , 1.2 mm ) than in single-bundle reconstruction ( mean , 4.1 mm ) . The mean side-to-side difference in KT-2000 arthrometer measurements was significantly less ( P = .014 ) in double-bundle reconstruction ( mean , 1.2 mm ) than in single-bundle reconstruction ( mean , 2.6 mm ) . The difference in the incidence of positive pivot-shift tests between group S ( 43 % ) and group D ( 16 % ) did not reach the level of statistical significance ( P = .058 ) . No significant differences in Lysholm score or Tegner score between the groups were observed . Conclusion : The rotatory stability of anatomic double-bundle reconstruction was significantly better than the rotatory stability of single-bundle reconstruction Background : While single-bundle anterior cruciate ligament reconstruction reduces anterior-posterior laxity , studies have demonstrated residual rotational instability . Improved pivot-shift results have been shown with the double-bundle graft ; however , no study has compared rotational laxity outcome of these surgical techniques in vivo under quantified , isolated torsional loading . Hypothesis : The anterior cruciate ligament – deficient knee exhibits greater rotational laxity than the contralateral uninjured knee . The double-bundle reconstruction restores rotational joint stability to a greater extent than single-bundle surgery . Study Design : Controlled laboratory study . Methods : Rotational laxity of 32 patients with unilateral anterior cruciate ligament injury was assessed in both knees at full extension and 30 ° of flexion using a magnetic resonance imaging – compatible torsional loading device . Patients were r and omly allocated either a single- or double-bundle reconstruction and reassessed 5 months after surgery . Results : The anterior cruciate ligament – deficient knees demonstrated greater laxity to internal rotational torque in the extended position , but not in the 30 ° flexed position . No significant differences in rotational laxity were found between single- and double-bundle reconstructions . In extension , excessive internal rotational laxity of injured compared with contralateral knees was reduced by anterior cruciate ligament reconstruction . The single-bundle reconstruction did not affect internal rotation compared with contralateral or preoperative groups . In response to internal rotational torque in the flexed knee position , the double-bundle reconstruction reduced laxity to 10.8 ° from the pre-operative value of 15.3 ° ( P = .058 ) ; postoperative rotation was also significantly less than the contralateral laxity of 16.4 ° ( P = .022 ) . Conclusion : The ruptured anterior cruciate ligament result ed in increased internal rotational laxity only in the extended position . The single-bundle reconstruction did not affect rotational restraint compared with contralateral or preoperative groups . The double-bundle procedure significantly reduced internal laxity in the flexed position when compared with normal . Clinical Relevance : As the anterior cruciate ligament is not the primary restraint to rotation , its contribution to joint stability is limited under isolated torsional load . While the double-bundle graft demonstrates superior rotational constraint , this may be excessive for isolated anterior cruciate ligament rupture Background Despite a number of studies comparing postoperative stability and function after anatomic double-bundle and single-bundle anterior cruciate ligament reconstruction ( ACLR ) , it remains unclear whether double-bundle reconstruction improves stability or function . Questions / purpose sWe therefore asked whether patients having single- and double-bundle ACLR using semitendinosus ( ST ) alone differed with regard to ( 1 ) postoperative stability ; ( 2 ) ROM ; and ( 3 ) five functional scores . Methods We prospect ively followed 60 patients with an isolated anterior cruciate ligament ( ACL ) injury . Thirty patients underwent single-bundle and 30 patients underwent double-bundle ACL reconstruction . Clinical ly we assessed stability and range of motion ( ROM ) ; anteroposterior stability was assessed by Rolimeter and rotational stability by a pivot shift test . Function was assessed by IKDC , Noyes , Lysholm , Marx , and Tegner activity scales . The minimum followup was 36 months ( mean , 46.2 months ; range , 36–60 months ) . Results Residual anteroposterior laxity at 3 years postoperatively was similar in both groups : 1.4 ± 0.3 mm versus 1.4 ± 0.2 mm , respectively . We observed no difference in the pivot shift test . ROM was similar in both groups , although double-bundle patients required more physical therapy sessions to gain full ROM . IKDC , Noyes , Lysholm , Marx , and Tegner scores were similar at final followup . Conclusion Double-bundle reconstruction of the ACL did not improve function or stability compared with single-bundle reconstruction . Level of Evidence Level II , therapeutic study . See Guidelines for Authors for a complete description of levels of evidence OBJECTIVE A nonr and omized clinical study was performed to compare the clinical and radiological outcome between double-bundle and single-bundle anterior cruciate ligament ( ACL ) reconstructions with semitendinosus tendon in athletes . MATERIAL AND METHODS We examined 70 patients with unilateral anterior cruciate ligament injury . They were followed up for a mean of 24 months . Each group of 35 patients underwent either double- or single-bundle ACL reconstruction . The mean age of the patients was 24.7 years ( range , 18 - 35 years ) . There were no differences between two groups regarding age at surgery , sex , follow-up period , period before surgery , combined meniscus injuries , athletic activity level , and International Knee Documentation Committee ( IKDC ) and Tegner scores . All patients followed the same postoperative program . They were evaluated using manual knee laxity tests , knee extension and flexion strength testing . General knee condition was evaluated by the IKDC and Tegner scores . RESULTS The results were excellent and good in 32 ( 91.4 % ) patients after double-bundle ACL reconstruction and in 30 ( 85.7 % ) patients after single-bundle ACL reconstruction , evaluating by IKDC system . However , statistical analysis showed no significant difference between the two groups regarding all IKDC-categorized data ( P=0.87 ) . The average scores of Tegner activity in double-bundle and single-bundle groups were 8.0 and 8.1 , respectively . CONCLUSIONS This trial showed no significant difference between the double and single-bundle ACL repairs PURPOSE A r and omized clinical study was conducted to compare the outcome between double-bundle ( DB ) and single-bundle ( SB ) anterior cruciate ligament ( ACL ) reconstructions with 4-str and semitendinosus tendon ( ST ) . METHODS We divided 68 patients with unilateral ACL injury into 2 groups according to their birth date , and they were followed up in person for a mean of 25 months ( range , 18 to 41 months ) . Each group of 34 patients underwent either DB or SB ACL reconstruction using 4-str and ST with EndoButton femoral fixation ( Smith & Nephew Endoscopy , And over , MA ) and anchor staple tibial fixation . There was no difference between the 2 groups with regard to age at surgery , sex , follow-up period , period before surgery , combined meniscus injuries , and athletic activity level . All patients followed the same postoperative program . They were evaluated using manual knee laxity tests , instrumented anterior laxity measurements ( KT-1000 arthrometer [ MEDmetric , San Diego , CA ] ) , knee extension and flexion strength testing , and so on . General knee condition was evaluated by use of the Lysholm knee score and subjective rating scale . RESULTS There were no significant differences between the 2 groups with regard to range of motion , thigh girth , muscle strength , and Lysholm score . Manual knee laxity testing revealed that negative Lachman and pivot-shift test results were found in more patients in the DB group than in the SB group . KT measurements averaged 2.4 mm in the SB group and 1.4 mm in the DB group , which was statistically significantly different . Statistical analysis showed no significant difference regarding all of the modified International Knee Documentation Committee-categorized data between the 2 groups . CONCLUSIONS This r and omized controlled trial indicated that DB ACL reconstruction via 4-str and ST is superior to the SB technique with regard to anterior and rotational stability ; however , it fails to show any subjective difference . LEVEL OF EVIDENCE Level I , prospect i ve r and omized controlled clinical study PURPOSE We performed this prospect i ve study to evaluate the incidence of meniscus tears arthroscopically and the effectiveness of magnetic resonance imaging ( MRI ) in detecting these lesions in patients with chronic anterior cruciate ligament (ACL)-deficient knees . METHODS We review ed 50 patients ( 46 male and 4 female ) with a mean age of 27 years ( range , 18 to 48 years ) who underwent ACL reconstruction for chronic ACL tears . Injuries were classified as chronic because arthroscopy was performed after more than 6 weeks of injury . All 50 patients had clinical and MRI evaluation followed by knee arthroscopy . The MRI and arthroscopic findings were then analyzed by a single independent review er . The presence of meniscus tears and their morphologic types and locations were analyzed . The sensitivity , specificity , positive predictive value , and negative predictive value of MRI were calculated . RESULTS On arthroscopy , a medial meniscus tear was found in 18 patients ( 36 % ) , a lateral meniscus tear was found in 11 patients ( 22 % ) , both menisci were torn in 8 patients ( 16 % ) , and no meniscus lesion was found in 13 patients ( 26 % ) . The most common morphologic type of tear seen in the medial meniscus was " complex " ( n = 11 [ 42 % ] ) , and that in the lateral meniscus was " longitudinal " ( n = 10 [ 53 % ] ) . The posterior horn of the meniscus was the most common tear site . The overall sensitivity , specificity , positive predictive value , and negative predictive value for detecting meniscus tears in chronic ACL-deficient knees on MRI were 90 % , 89 % , 87 % , 93 % , respectively . CONCLUSIONS We conclude from our study that in chronic ACL-deficient patients , the prevalence of posterior horn medial meniscus tears seems to be high . Anterior horn tears and radial and horizontal patterns of meniscus tears seem to be rare in chronic ACL deficiency . MRI correlates well with arthroscopy and has high negative predictive values . LEVEL OF EVIDENCE Level I , prognostic prospect i ve study BACKGROUND In clinical studies there is still a lot of controversy about the increased anterior and rotational stability between double-bundle ( DB ) and single-bundle ( SB ) anterior cruciate ligament ( ACL ) reconstruction . The aim of this study was to evaluate the clinical results of four-tunnel DB ACL reconstruction . METHODS Sixty-four consecutive patients with ACL ruptures from May 2005 to May 2006 were r and omly assigned into two groups : 32 cases for SB ACL reconstruction and 32 cases for DB ACL reconstruction . Clinical data , including KT 2000 , Biodex test , Lysholm score , Tegner score and IKDC score , were prospect ively collected until at least 10 months post-operative . RESULTS The average values of KT 2000 were ( 1.47 + /- 1.17 ) mm and ( 1.68 + /- 1.14 ) mm for the SB and DB ACL reconstruction groups at 30 degrees of knee flexion ( P > 0.05 ) , and were ( 1.04 + /- 0.98 ) mm and ( 1.13 + /- 0.98 ) mm at 90 degrees of knee flexion ( P > 0.05 ) . There were also no significant differences in Lysholm score , Tegner score , IKDC score and Biodex test scores between the two groups ( P > 0.05 ) . The operation time of DB ACL reconstruction was 20 minutes longer than the SB ACL reconstruction ( P < 0.05 ) . CONCLUSION Double bundle ACL reconstructions have no obvious clinical advantages over single bundle ACL reconstructions BACKGROUND While traditional surgical repair of the anterior cruciate ligament is able to restore anterior-posterior knee stability , laxity in the transverse plane remains . Double-bundle reconstruction has demonstrated greater rotational restraint than the single-bundle technique under passive loading conditions ; however , no comparison has been made under physiological weight-bearing conditions . The purpose of this study was to determine differences in rotational knee kinematics during a dynamic task in patients who had received either a single- or double-bundle reconstruction . METHODS Twenty-two patients exhibiting isolated anterior cruciate ligament rupture were r and omly allocated either a single or double-bundle reconstruction . Three-dimensional knee kinematics were measured during a dynamic cutting activity prior to and following surgery . Functional range of rotation was compared between groups pre- and post-operatively and kinematics were assessed against uninjured control subjects . FINDINGS No difference in overall range of rotation was found under physiological loading conditions . However , a significant interaction of the midpoint of the range of movement was observed ; a greater external rotational shift in the single-bundle group followed reconstruction , while the kinematics of the double-bundle patient group shifted closer to those of the control group . INTERPRETATION The double-bundle reconstruction demonstrated superior outcome in rotational kinematics to the single-bundle technique Purpose Based on biomechanical anatomical studies , double-bundle reconstruction of the anterior cruciate ligament ( ACL ) was introduced to achieve better stability in the knee , particularly in respect of rotatory loads . An in vivo , computer-assisted , double-bundle ( DB ) ACL reconstruction is superior to a single-bundle ( SB ) ACL reconstruction at reducing rotatory , and AP laxities of the tibia at 20 degrees of knee flexion and also during the pivot shift test . Methods The data of 63 patients who had ACL reconstruction were prospect ively collected . Thirty-two patients had single-bundle reconstruction ( SB group ) , and 31 received double-bundle reconstruction ( DB group ) . The per-operative navigation system ( Praxim ACL surgetics System ) helped to search for a minimal anisometry profile of the grafts , which was favorable ( graft loosened with flexion ) in the anatomic area of ACL insertion and preventing any conflict between the graft and the femoral notch . The system also evaluated anteroposterior ( AP ) rotational stabilities and pivot shift . The value of the pivot shift was calculated from the values of the maximum rotation and AP translation obtained when performing the manoeuver before and after ACL reconstruction , comparing SB and DB reconstruction . Results The post-operative AP displacement of the lateral compartment during the Lachman test was statistically reduced in DB group in comparison with SB group ( 5.1 ± 4.4 mm vs. 7.1 ± 3.2 mm , P = 0.04 ) , whereas the AP displacements of the medial compartment were also reduced ( 3.4 ± 3.7 mm vs. 4.5 ± 2.6 mm , P = 0.15 ) but with no statistical significance . Internal and external rotations at 20 ° of knee flexion were lower in the DB group than in SB group with statistical significance ( respectively , 13.2 ± 4.9 ° vs. 17.5 ± 4.0 ° , P < 0.001 and 9.1 ± 3.6 ° vs. 11.5 ± 3.5 ° , P = 0.01 ) . During the pivot shift test , the post-operative AP maximal translation was statistically different in both groups : 4.5 ± 2.1 mm in DB group and 6.3 ± 2.7 mm in SB group ( P = 0.01 ) ) , whereas the maximal rotation was not statistically different : 3.8 ± 2.5 ° in DB group and 3.4 ± 1.2 ° in SB group ( n.s . ) . Therefore , Colombet ’s index was similar in DB group and SB group ( respectively , 0.21 ± 0.16 and 0.17 ± 0.06 , ( n.s . ) ) . Conclusions This study shows a significant intraoperative advantage in anterior and rotational stability for four-tunnel DB ACL reconstruction compared with SB ACL reconstruction . Level of evidence II Patellar tendon autografts are not suitable for multibundle ACL reconstruction , a procedure that reportedly enhances postoperative knee stability . Biomechanical studies recommend lateral placement of the femoral tunnel for single-bundle reconstruction to improve postoperative knee kinematics . We asked whether a lateralized single-bundle patellar tendon graft ( LSBP ) would provide good short-term results of ACL reconstruction comparable to double-bundle hamstring tendon grafts ( DBH ) . We prospect ively followed 144 patients with unilateral ACL rupture treated with either LSBP or DBH in a nonr and omized fashion . Twenty-four female and 31 male patients with LSBP and 44 female and 26 male patients with DBH were followed for a minimum of 24 months ( average , 38 months ; range , 24–56 months ) . The patients with LSBP recovered knee extension better at 1 month compared with the patients with DBH , but extension was similar after 3 months . We observed no differences in the side-to-side difference of KT1000 ™ measurement , pivot shift test , or anterior drawer test between LSBP and DBH . Although better recovery of hamstring strength in LSBP and better recovery of quadriceps strength in DBH were observed in the early postoperative period , these differences disappeared after 12 months . There was no difference in International Knee Documentation Committee objective evaluation between LSBP and DBH at the final followup . Level of Evidence : Level II , therapeutic study . See the Guidelines for Authors for a complete description of levels of evidence |
1,267 | 24,085,611 | There is some evidence that the use of a facemask to correct prominent lower front teeth in children is effective when compared to no treatment on a short-term basis . | BACKGROUND Prominent lower front teeth ( termed reverse bite ; under bite ; Class III malocclusion ) may be due to a combination of the jaw or tooth positions or both .
The upper jaw ( maxilla ) can be too far back or the lower jaw ( m and ible ) too far forward , or both .
Prominent lower front teeth can also occur if the upper front teeth ( incisors ) are tipped back or the lower front teeth are tipped forwards , or both .
Various treatment approaches have been described to correct prominent lower front teeth in children and adolescents .
OBJECTIVES To assess the effects of orthodontic treatment for prominent lower front teeth in children and adolescents . | INTRODUCTION The aim of this prospect i ve clinical study was to evaluate the skeletal , dentoalveolar , and soft-tissue effects of maxillary protraction with miniplates compared with conventional facemask therapy and an untreated Class III control group . METHODS Forty-five subjects who were in prepubertal or pubertal skeletal growth periods were included in the study and divided into 3 groups of 15 patients each . All subjects had skeletal and dental Class III malocclusions with maxillary deficiency , vertically normal growth pattern , anterior crossbite , Angle Class III molar relationship , normal or increased overbite , and retrusive nasomaxillary complex . Before maxillary protraction , rapid maxillary expansion with a bonded appliance was performed in both treatment groups . In the first group ( MP+FM ) , consisting of 5 girls and 10 boys ( mean age , 10.91 years ) , facemasks were applied from 2 titanium miniplates surgically placed laterally to the apertura piriformis regions of the maxilla . The second group ( FM ) of 7 girls and 8 boys ( mean age , 10.31 years ) received maxillary protraction therapy with conventional facemasks applied from hooks of the rapid maxillary expansion appliance . The third group of 8 girls and 7 boys ( mean age , 10.05 years ) was the untreated control group . Lateral cephalometric films were obtained at the beginning and end of treatment or observation in all groups and analyzed according to a structural superimposition method . Measurements were evaulated statistically with Wilcoxon and Kruskal-Wallis tests . RESULTS Treatment periods were 6.78 and 9.45 months in the MP+FM and FM groups , respectively , and the observation period in the control group was 7.59 months . The differences were significant between the 3 groups ( P < 0.05 ) and the MP+FM and FM groups ( P < 0.001 ) . The maxilla moved forward for 2.3 mm in the MP+FM group and 1.83 mm in the FM group with maxillary protraction . The difference was significant between 2 groups ( P < 0.001 ) . The protraction rates were 0.45 mm per month in the MP+FM group and 0.24 mm per month in the FM group ( P < 0.001 ) . The maxilla showed anterior rotation after facemask therapy in the FM group ( P < 0.01 ) ; there was no significant rotation in the MP+FM group . Posterior rotation of the m and ible and increased facial height were more evident in the FM group compared with the MP+FM group ( P < 0.01 ) . Both the maxilla and the m and ible moved forward significantly in the control group . Protrusion and mesialization of the maxillary teeth in the FM group were eliminated in the MP+FM group . The maxillom and ibular relationships and the soft-tissue profile were improved remarkably in both treatment groups . CONCLUSIONS The undesired effects of conventional facemask therapy were reduced or eliminated with miniplate anchorage , and efficient maxillary protraction was achieved in a shorter treatment period The aim of this research was to evaluate , within a controlled clinical study , the effects of a Delaire-type facemask or a modified Jasper Jumper ( JJ ) used in the treatment of children with Class III malocclusions due to maxillary retrognathia on temporom and ibular disorders ( TMDs ) . Forty-six patients with Class III malocclusions referred for orthodontic treatment were divided into two groups , a test and a control . The test group comprised 33 r and omly chosen patients ( 15 females , 18 males ) aged 8 - 11 years . The control group included 13 patients ( eight females , five males ) with similar features . TMD assessment was performed before and after treatment using a two-axis question naire , the Research Diagnostic Criteria for Temporom and ibular Disorders ( RDC/TMDs ) . Qualitative data were evaluated using chi-square and McNemar tests . No statistically significant differences related to the presence of TMD were observed pre- or post-treatment ( P > 0.05 ) . The most commonly encountered diagnosis was arthralgia in the JJ group both before and after treatment . Evaluation of joint and muscle regions showed decreased symptoms , apart from the diagnosed discomforts , in the JJ group ( P < 0.05 ) . Reduced symptoms were observed in the Delaire group ; however , this reduction was not statistically significant . An increase , not considered to be statistically significant , was observed in the control group . The Delaire-type facemask and modified JJ used in the early phase of Class III malocclusion treatment did not result in TMD Background and Objective : When treating pronounced dentoalveolar compensation of a skeletal Class III malocclusion , preoperative decompensation frequently requires the extraction of maxillary lateral teeth and retraction of the incisors . In this context , maximum anchorage of the maxillary molars is frequently necessary to attain the significant increase in negative overjet that is desired . The aim of this study was to compare the quality of conventional and skeletal molar anchorage using mini-implants in association with pre-operative decompensation . Patients and Methods : Pre-operative decompensation involved the symmetric extraction of two lateral teeth from the maxilla as well as retraction of the front teeth in each of 20 patients with a marked skeletal Class III . The molar anchorage half of the patients received was conventional ( transpalatal arch ) while the other half were treated with skeletal anchorage via mini-implants inserted in the anterior palate . Study models were prepared and analyzed using a 3D scanner before and after space closure ( OrthoProof ) . We analyzed the bilateral degree of mesial molar migration and change in the transversal dimension ( DigiModel software ) . Results : All patients demonstrated mesial migration of the upper molars as a response to the load on the anchorage unit . The 4.21 mm ( ± 1.17 mm ) anchorage loss associated with conventional anchorage was greater than that of skeletal anchorage in the anterior palate ( 2.05 mm [ ± 1.39 mm ] ) . We observed a tendency towards transversal expansion in the molar region according to the design and thickness of the transpalatal arch . Conclusions : Skeletal molar anchorage proved to be more effective than the conventional anchorage . Hence , skeletal anchorage is preferable , especially when patients are in serious need of preoperative decompensation . The anterior palate has proven to be an advantageous region for insertion in conjunction with the correct mechanics . ZusammenfassungFragestellung : Bei ausgeprägten dentoalveolären Kompensationen einer skelettalen Klasse III ist i m Rahmen der prächirurgischen Dekompensation oftmals die Extraktion von Oberkiefer-Seitenzähnen mit Retraktion der Front indiziert . Die in diesem Rahmen gewünschte signifikante Vergrößerung der negativen sagittalen Frontzahnstufe erfordert oft eine maximale Verankerung der Oberkiefermolaren . Ziel dieser Studie war der Vergleich der Qualität der konventionellen und skelettalen Molarenverankerung mittels Mini-Implantaten i m Rahmen der präoperativen Dekompensation . Patienten und Method ik : Bei 20 Patienten mit einer ausgeprägten skelettalen Klasse III wurden zur präoperativen Dekompensation symmetrisch jeweils zwei Seitenzähne i m Oberkiefer extrahiert sowie eine Frontretraktion durchgeführt . Die Molarenverankerung erfolgte bei der einen Hälfte der Patienten jeweils mittels konventioneller Verankerung ( Transpalatinalbogen ) und bei der and eren Hälfte skelettal mittels Mini-Implantaten i m anterioren Gaumen . Vor und nach dem Lückenschluss wurden Studienmodelle angefertigt und mittels eines 3D-Scanners ( Ortho-Proof ) vermessen . Sowohl das beidseitige Ausmaß der Mesialw and erung der Molaren als auch eine Veränderung in der Transversalen wurden ausgewertet ( DigiModel Software).Ergebnisse : Bei allen Patienten kam es bei Belastung der Verankerungseinheit zu einer Mesialw and erung der Oberkiefermolaren . Bei konventioneller Verankerung war der Verankerungsverlust mit 4,21 mm ( ± 1,17 mm ) größer als bei skelettaler Verankerung i m anterioren Gaumen mit 2,05 mm ( ± 1,39 mm ) . Je nach Design und Stärke des Transpalatinalbogens zeigte sich eine Tendenz zur transversalen Erweiterung i m Molarenbereich . Schlussfolgerungen : Die skelettale Molarenverankerung zeigte eine höhere Effektivität als die konventionelle Verankerung . Insbesondere bei Patienten mit einem großen Bedarf an präoperativer Dekompensation sollte daher der skelettalen Verankerung der Vorzug gegeben werden . Der anteriore Gaumen erwies sich in Kombination mit einer geeigneten Mechanik für diese Aufgabe als vorteilhafte Insertionsregion The aim of this study was to evaluate and compare the dentofacial effects of 1 week rapid palatal expansion ( RPE ) and activation-deactivation ( A/D ) RPE protocol s with reverse headgear ( RH ) . Two groups , each containing 15 subjects , were included in this study . In the RPE group ( seven males and eight females , 11.94 ± 1.62 years ) , Hyrax screws were activated every 12 hours for 1 week . At the end of this period , RPE was stopped and the patients were instructed to wear the RH . In the A/D-RPE group ( seven males and eight females , 11.34 ± 1.81 years ) , the screws were activated every 12 hours for 1 week . Subsequently , the screws were deactivated every 12 hours for 1 week followed by activation and deactivation for the following 2 weeks . After this protocol , the patients were instructed to use the RH . A total force of 700 g was applied to both groups for 16 - 18 hours/day for the first 3 months , for 12 hours/day for the second 3 months , and for 6 hours/day for the second 6 months . Lateral cephalometric films were taken before treatment ( T1 ) and at the end of the first ( T2 ) and second ( T3 ) 6 months to evaluate the dentofacial changes . Intragroup differences of each l and mark at T2-T1 , T3-T2 , and T3-T1 were analysed with a paired t-test ( P < 0.016 ) , and intergroup differences were compared with an independent t-test ( P < 0.05 ) . Anterior movement of point A ( 4.13 mm ) for the A/D-RPE group was approximately twice of the RPE group ( 2.33 mm ; P < 0.001 ) . Backward movement of the m and ible showed no significant difference between the groups . Anterior face height increases did not demonstrate significant differences between the groups . The pronounced anterior movement of point A demonstrates that the A/D-RPE procedure positively affects maxillary protraction The aims of this study were to evaluate ( i ) the effect of ethnicity , social deprivation , and normative orthodontic treatment need on orthodontic aesthetic self-perception , self-perceived need for orthodontic treatment , and oral aesthetic impact of malocclusion ; ( ii ) the effect of ethnicity , social deprivation , and gender on perceived orthodontic treatment need and use of orthodontic services ; ( iii ) the influence of perceived oral aesthetic impact of malocclusion on perceived need and wish for orthodontic treatment ; and ( iv ) whether orthodontic treatment experience influences perceived oral aesthetic impact of malocclusion . A stratified , r and om sample of 434 14 - 15-year-old children from schools in Manchester , UK , was obtained . Information was collected on orthodontic aesthetic self-perception and orthodontic treatment experience using a question naire . The former data were combined to form an Oral Aesthetic Subjective Impact Scale ( OASIS ) . Normative orthodontic treatment need was measured with the Index of Orthodontic Treatment Need ( IOTN ) . Children with higher clinical need for orthodontic treatment perceived themselves as worse off than their peers with lower need . More socially deprived children or those with high IOTN aesthetic component ( AC ) scores had a higher ( i.e. more negative ) aesthetic impact ( OASIS ) score . Asians and females had higher IOTN dental health component ( DHC ) scores , but a better aesthetic appearance than Caucasians and males . More deprived children were less likely to have received orthodontic treatment . Despite this , OASIS scores were similar between treated and untreated children . Untreated children who wished for orthodontic treatment had higher IOTN AC and OASIS scores INTRODUCTION In this cephalometric investigation , we analyzed the treatment effects of bone-anchored maxillary protraction ( BAMP ) with miniplates in the maxilla and m and ible connected by Class III elastics in patients with Class III malocclusion . METHODS The treated sample consisted of 21 Class III patients consecutively treated with the BAMP protocol before the pubertal growth spurt ( mean age , 11.10 ± 1.8 years ) and reevaluated after BAMP therapy , about 1 year later . The treated group was compared with a matched control group of 18 untreated Class III subjects . Significant differences between the treated and control groups were assessed with independent- sample t tests ( P < 0.05 ) . RESULTS Sagittal measurements of the maxilla showed highly significant improvements during active treatment ( about 4 mm more than the untreated controls ) , with significant protraction effects at orbitale and pterygomaxillare . Significant improvements of overjet and molar relationship were recorded , as well as in the m and ibular skeletal measures at Point B and pogonion . Vertical skeletal changes and modifications in incisor inclination were negligible , except for a significant proclination of the m and ibular incisors in the treated group . Significant soft-tissue changes reflected the underlying skeletal modifications . CONCLUSIONS Compared with growth of the untreated Class III subjects , the BAMP protocol induced an average increment on skeletal and soft-tissue advancement of maxillary structures of about 4 mm , and favorable m and ibular changes exceeded 2 mm INTRODUCTION The purpose of this controlled r and omized clinical trial was to quantify the effects of maxillary protraction with or without palatal expansion . METHODS Forty-six children aged 5 to 10 years were r and omly assigned to 1 of 3 groups : ( 1 ) facemask with palatal expansion , ( 2 ) facemask without palatal expansion , and ( 3 ) observation for 12 months . Cephalometric analysis with traditional cephalometric measurements , an x-y coordinate system , and an occlusal-plane analysis were used . RESULTS Student t tests showed no significant differences ( P < .05 ) between expansion and nonexpansion groups in any measured variable . Comparisons of treated and control subjects showed significant ( P < .01 ) treatment effects beyond normal Class III growth . Analysis of x-y coordinate variables showed the following : 2 mm additional forward displacement of the maxillary complex with counterclockwise rotation , m and ibular clockwise rotation , posterior movement of B-point by an average of 1.5 mm , and forward movement of the maxillary dentition of nearly 1 mm . Analysis of traditional cephalometric measures showed improvements in ANB angle of nearly 4 degrees and Wits appraisal of nearly 4 mm . The occlusal plane analysis showed an apical base change of 4 mm , 1.5 mm forward displacement of the maxillary complex , m and ibular clockwise rotation of 2.5 mm , and forward maxillary molar movement of 1.9 mm . CONCLUSIONS The results of this continuing 5-year clinical trial indicate that early facemask therapy , with or without palatal expansion , is effective to correct skeletal Class III malocclusions INTRODUCTION The objective of this study was to evaluate the effectiveness of the light-force chincup appliance in correcting the skeletal and dentoalveolar components of Class III malocclusion compared with an untreated Class III control group . METHODS The treatment sample consisted of 26 patients ( 11 boys , 15 girls ) treated with the light-force chincup ( 125 - 250 g ) . The mean age at the start of treatment in the chincup group was 8.5 years , with posttreatment cephalograms taken on average 2.6 years later . The control group consisted of 20 subjects . The mean age at the start of observation for the control group ( 6 boys , 14 girls ) was 7.3 years , and the mean time of observation was 2.4 years . Lateral cephalograms were analyzed with a specific tracing regimen at the 2 time points for both groups . Treatment outcome were determined . The treatment group subsequently was subdivided into those treated simultaneously with a quad-helix appliance and those with the chincup only . Mann-Whitney U tests for independent sample s were performed to evaluate the differences between the treated and untreated groups at both time points , the changes between the 2 time points , and the differences between the groups treated with the quad-helix and chincup , and the chincup only . RESULTS The chincup sample showed no significant skeletal changes in the m and ible in either the vertical or horizontal direction , except for a slight decrease in SNB angle and an increase in ANB angle . There were significant dentoalveolar changes , particularly uprighting of the m and ibular incisors . Significant positive Class III treatment outcomes were recorded in the quad-helix group , including a decrease in m and ibular length of 1.9 mm compared with the chincup group . CONCLUSIONS Fewer than 50 % of the subjects treated with the chincup had favorable clinical outcomes . Correction of the initial Class III malocclusion occurred through significant dentoalveolar changes . The light-force chincup did not produce orthopedic changes in the m and ible . Maxillary expansion with a quad-helix might aid in the correction of the Class III malocclusion in conjunction with the chincup The aim of this study was to examine the effect of varying the force direction on maxillary protraction . A total of 20 patients with class III maxillary retrognathism were r and omly divided into two groups . Group 1 was comprised of nine patients with a mean age of 8.58 years , and group 2 was composed of 11 patients with a mean age of 8.51 years . Both groups received a cap splint-type rapid palatal exp and er and the screw was activated twice a day for 10 days . After the expansion procedure the face mask protraction procedure was initiated . In group 1 , we applied the force intraorally from the canine region with a forward and downward direction at a 30 degrees angle to the occlusal plane . In group 2 , the force was applied extraorally 20 mm above the maxillary occlusal plane . In both groups a unilateral 500 g force was applied and the patients were instructed to wear the face mask for 16 h/d for the first three months and 12 h/d for the next three months . The Wilcoxon sign rank test was used to evaluate the effect of the two different face masks , and a Mann-Whitney U-test was carried out to evaluate the differences between the two groups . The results showed that both force systems were equally effective to protract the maxilla ; however , in group I we observed that the maxilla advanced forward with a counter-clockwise rotation . In group 2 we observed an anterior translation of maxilla without rotation . The dental effects of both methods were also different . The maxillary occlusal plane did not rotate in group 1 , in contrast to the clockwise rotation in group 2 . The maxillary incisors were proclined slightly in group 1 , but in contrast they were retroclined and extruded in group 2 . In conclusion , the force application from near the center of resistance of the maxilla was an effective method to prevent the unwanted side effects , such as counter-clockwise rotation of the maxilla , in group 1 . The group 2 results suggest that this method can be used effectively on patients who present as class III combined with an anterior open bite The material of this investigation consisted of 40 functional Class III malocclusion subjects . Each treatment and control group consisted of 20 Class III cases ( 10 boys and 10 girls ) . The mean age of the subjects in the function regulator , FR-3 , group was 9.5 years at the beginning of the treatment , and in the control group 9.3 years at the beginning of the observation period . The mean treatment period of the FR-3 group was 1.9 years and the mean observation period of the control group is 1.8 years . In this study , as a result of FR-3 appliance therapy in the functional Class III malocclusion group , the negative overjet that was present at the beginning of the treatment has been converted into a positive overjet by an average increase of 3.8 mm at the end of the treatment . The sum of downward and backward rotation of the m and ible , the decrease in the SNB angle with a subsequent increase of the ANB angle , and the retrusion of the lower incisors were effective in the increase of the overjet . The increase in the SNA angle and the protrusion of the upper incisors were found to be insignificant . The overbite decreased due largely to the downward and backward rotation of the m and ible Objective To investigate the effectiveness of early class III protraction facemask treatment in children under 10 years of age . Design Multicentre , r and omized controlled trial Setting Eight UK hospital orthodontic units . Subjects and methods Seventy‐three patients were r and omly allocated , stratified for gender , into an early class III protraction facemask group ( PFG ) ( n = 35 ) and a control/no treatment group ( CG ) ( n = 38 ) . Outcomes Dentofacial changes from lateral cephalograms and occlusal changes using the peer assessment rating ( PAR ) . Self‐esteem was assessed using the Piers – Harris children 's self‐concept scale , and the psychosocial impact of malocclusion with an oral aesthetic subjective impact scores ( OASIS ) question naire . Temporom and ibular joint ( TMJ ) signs and symptoms were also recorded . The time points for data collection were at registration ( DC1 ) and 15 months later ( DC2 ) . Results The following mean skeletal and occlusal changes occurred from the class III starting point : SNA , PFG moved forwards 1·4 ° ( CG forward 0·3 ° ; P = 0·018 ) ; SNB , PFG moved backwards −0·7 ° ( CG forward 0·8 ° ; P<0·001 ) ; ANB , PFG class III base improved + 2·1 ° ( CG worsened by −0·5 ° ; P<0·001 ) . This contributed to an overall difference in ANB between PFG and CG of 2·6 ° in favour of early protraction facemask treatment . The overjet improved + 4·4 mm in the PFG and marginally changed + 0·3 mm in the CG ( P<0·001 ) . A 32·2 % improvement in PAR was shown in the PFG and the CG worsened by 8·6 % . There was no increased self‐esteem ( Piers – Harris score ) for treated children compared with controls ( P = 0·22 ) . However , there was a reduced impact of malocclusion ( OASIS score ) for the PFG compared with the CG ( P = 0·003 ) , suggesting treatment result ed in slightly less concern about the tooth appearance . TMJ signs and symptoms were very low at DC1 and DC2 and none were reported during active facemask treatment . Conclusions Early class III orthopaedic treatment , with protraction facemask , in patients under 10 years of age , is skeletally and dentally effective in the short term and does not result in TMJ dysfunction . Seventy per cent of patients had successful treatment , defined as achieving a positive overjet . However , early treatment does not seem to confer a clinical ly significant psychosocial benefit 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 The aim of this investigation was to study cephalometrically the skeletal , dental and soft tissue modifications induced by a Delaire facemask and Bionator III appliance in a sample of 30 patients ( 17 boys and 13 girls ) , aged 4.1 - 9 years [ mean 5.85 years , confidence interval ( CI ) 5.41 - 6.29 ] , in the early mixed dentition with a skeletal Class III malocclusion caused by maxillary retrognathism ( group 1 ) and compared with a control sample of 24 subjects ( 14 boys and 10 girls ) , aged 4 - 9 years ( mean 5.97 years , CI 5.35 - 6.58 ) with untreated Class III malocclusions ( group 2 ) . For each patient a lateral cephalogram was taken before treatment ( T0 ) , after facemask removal ( T1 ) , and at the end of the retention period with a Bionator III ( T2 ) . Cephalometric analysis was carried out . The post-treatment cephalometric values in the treated group showed a forward displacement of the maxilla result ing in a statistically significant increase ( P < 0.001 ) in the SNA angle , A-NPg ( mm ) and PNS-A ( mm ) linear values . There was a clockwise rotation of the m and ible , with a decrease in the SNB angle and a satisfactory correction of the Class III relationship . The beneficial effects on the facial profile were confirmed by an increase in UL-EL distance and in NB -- HL and NsPgs -- HL angles , and by a decrease in the facial convexity angle . These findings indicate that the Delaire facemask and Bionator III treatment is effective for correcting skeletal Class III malocclusions caused by maxillary retrognathism in the early mixed dentition In this study , the clinical effects of two extra-oral orthopaedic appliances were compared cephalometrically . Lateral cephalograms of 60 individuals were used in this investigation . The study group was r and omly divided into three parts as a ) control , b ) m and ibular headgear and c ) chin-cap groups . The subjects of the study group were selected among Class III , low angle or vertically normally growing individuals . The total observation period was one year . Results showed that both appliances were effective skeletally , but there were some differences between them . The results are as follows ; chin-cap therapy led to an inhibition in the development of the upper face and an effective control of the vertical dimension in addition to the posterior positioning of the m and ible . M and ibular headgear inhibited general growth and development of the m and ible and showed an increase in lower anterior face height and also , a significant lower molar distalization was found INTRODUCTION The aim of this prospect i ve clinical trial was to assess the effects of varying force directions on the dynamic measurement of natural head position and orofacial airway dimensions of Class III patients during maxillary orthopedic protraction compared with an untreated control group . METHODS The conventional facemask group comprised 15 patients ( 8 girls , 7 boys ; mean age , 9.6 ± 1.3 years ) , the modified facemask group comprised 15 patients ( 7 girls , 8 boys ; mean age , 9.5 ± 1.5 years ) , and the control group comprised 15 subjects ( 7 girls , 8 boys ; mean age , 9.8 ± 1.6 years ) . Natural head position measurements and cephalometric records were obtained from all subjects before and after treatment or the control period ( approximately 1 year ) . An inclinometer and a portable data logger were used to collect the dynamic natural head position data . For statistical comparisons , paired sample s t tests , analysis of variance ( ANOVA ) , and post-hoc Tukey tests were used at the P < 0.05 level . RESULTS Both treatment groups showed statistically significant changes in the sagittal ( pitch ) measurements of natural head position and upper pharynx , aerial , and total area of airway measurements during the treatment period . In the control group , the only statistically significant change was an increased upper pharynx measurement ( P = 0.020 ) . According to the intergroup comparisons , statistically significant natural head position differences were found in the conventional ( 6.4 ° flexion ) and the modified ( 5.7 ° flexion ) facemask groups when compared with the controls . The modified facemask group also showed significant changes in aerial ( P = 0.003 ) and total ( P < 0.001 ) areas of the airway measurements compared with the control group . No statistically significant differences were observed between the 2 treatment groups . CONCLUSIONS These findings suggest that modified and conventional facemask therapy with expansion have significant cranial flexion effects on the dynamic measurements of natural head position . Additionally , the modified facemask procedure showed significant effects on the orofacial airway dimensions compared with the initial values and the values of the untreated controls INTRODUCTION The aim of this study was to compare the effects of facemask treatment with and without expansion in patients with skeletal Class lll malocclusion . METHODS The material for this study consisted of the pretreatment and posttreatment lateral cephalograms of 28 subjects with skeletal and dental Class lll malocclusions , divided into 2 groups of 14 . In the facemask with expansion group ( FMEXP ; 8 girls , 6 boys ; mean age , 11 years 1 month ) , each subject wore a Delaire-type facemask and a bonded rapid maxillary expansion appliance . In the facemask only group ( FM ; 8 girls , 6 boys ; mean age , 11 years 6 months ) , each subject wore a Delaire-type facemask with a removable appliance . A third group of untreated children with Class lll malocclusion ( 7 girls , 7 boys ; mean age , 10 years 2 months ) was used as the control sample . RESULTS The forward displacement of the maxilla in both treated groups was significantly greater than in the control group . The forward displacement of pogonion and increase in facial depth in the control group showed significant differences compared with the treatment groups . Extrusion of the maxillary molars was significantly greater in the FM group than in the control group . The increase in the m and ibular plane angle and the decrease in the facial axis were significantly different between the FMEXP group and the control group . Molar relationship increased more in the FM group than in the FMEXP group ; this was the only significant difference between the treatment groups . In both treatment groups , dental and skeletal treatment of subjects with Class lll malocclusion were achieved . CONCLUSIONS If the treatment indications are appropriate , facemask therapy can be an effective method for Class III treatment |
1,268 | 17,443,519 | AUTHORS ' CONCLUSIONS There is evidence of a significant reduction in mortality from AAA in men aged 65 to 79 years who undergo ultrasound screening .
There is insufficient evidence to demonstrate benefit in women . | BACKGROUND Abdominal aortic aneurysm ( AAA ) is found in 5 % to 10 % of men aged 65 to 79 years .
The major complication is rupture which presents as a surgical emergency .
The mortality after rupture is high , 80 % for patients reaching hospital and 50 % for those undergoing surgery for emergency repair .
Currently elective surgical repair is recommended for aneurysms discovered to be larger than 5.5 cm to prevent rupture .
There is interest in population screening to detect , monitor and repair abdominal aortic aneurysms before rupture .
OBJECTIVES To determine the effects of screening asymptomatic individuals for AAA on mortality , subsequent treatment , quality of life and cost effectiveness of screening . | INTRODUCTION Macrolide treatment has been reported to reduce the risk of recurrent ischaemic heart disease . The influence of a macrolide on the expansion rate of small abdominal aortic aneurysms ( AAA ) is unknown at present . The aim of this study was to investigate the effect of roxithromycin on the expansion rate of small AAA . MATERIAL S AND METHODS A total of 92 patients with a small AAA were recruited from two population s. One population consisted of 6.339 men aged 65 - 73 years who were offered participation in a mass screening programme for AAA at the local hospital . From this population 66 subjects were recruited . The remaining 26 were recruited from among 49 subjects diagnosed at interval screening for an initial aortic diameter between 25 mm and 29 mm . The patients were r and omized to receive either oral roxithromycin 300 mg once daily for 28 days or matching placebo , and followed for a mean of 1.5 years . RESULTS During the first year the mean annual expansion rate of AAA was reduced by 44 % in the macrolid group ( 1.56 mm/year ) compared to 2.80 mm/year after placebo ( p = 0.02 ) . During the second year the difference was only 5 % . Multiple linear regression analysis showed that roxithromycin treatment and initial AAA size were significantly related to AAA expansion when adjusted for smoking , diastolic blood pressure , and IgA level > or = 20 . The logistic regression analysis confirmed a significant difference in expansion rates above 2 mm annually between the intervention and placebo groups , OR = 0.09 ( 95 % CI : 0.01 - 0.83 ) . DISCUSSION In comparison to placebo , roxithromycin 300 mg daily for four weeks reduced the expansion rate of AAA BACKGROUND To study the propranolol treatment of small abdominal aortic aneurysms ( AAA ) concerning intention to treat , side effects , and inhibition of expansion . METHODS DESIGN Two-year lasting prospect i ve r and omised double-blinded intervention trial . SETTING Hospital-based mass screening for AAA with annual ambulatory control of small AAA . PARTICIPANTS Of 122 screening-diagnosed small AAA , 51 ( 42 % ) were excluded because of contraindications or present beta-blockage , and 17 refused participation . Thus , 54 ( 44.3 % ) were included . INTERVENTION Participants were r and omised to 40 mg propranolol twice a day or placebo . MEASURES The same observed was used to follow-up AAA-expansion , side effects , quality of life ( QL ) , branchial and ankle blood pressure ( ABI ) , and pulmonary function ( FEV1 and FVC ) . RESULTS Sixty percent in the propranolol group , and 25 % in the placebo group dropped out , mainly caused by dyspnoea in the propranolol group ( RR=1.74 , 95 % C.I. : 1.06 - 2.86 ) . Five ( 16.7 % ) died in the propranolol group , while 1 ( 4.2 % ) died in the placebo group ( RR=1.6 ( 1.02 - 2.51 ) ) . Furthermore , decreased pulmonary function , ABI , and QL was noticed in the propranolol group . Consequently , the trial was stopped after two years . Ninety-five percent of the measurements of the AAA were measured within 2 mm variation . If expansion was defined as above 2 mm annually , the relative risk of expansion in the placebo group was 1.17 ( 0.74 - 1.85 ) , and 2.44 ( 0.88 - 6.77 ) among the non-drop-outs . CONCLUSIONS Only 22 % of small screenings-diagnosed AAA were treatable with propranolol for two years . Consequently , only large scale studies are capable of showing potential minor inhibition of expansion by propranolol . However , whether such treatment ever becomes ethically acceptable is debatable Objectives — To assess the importance of the private costs incurred by patients when making a judgment on the economics of screening for abdominal aortic aneurysm ( AAA ) , and to explore the variation in such costs depending on screening location . Setting — A district general hospital and general practitioner surgeries . Methods — Four hundred and ninety nine consecutive subjects attending for AAA screening completed a question naire asking about travel arrangements for the journey to and from the clinic , the distance travelled , the time taken , the mode of transport , and any out-of-pocket expenses incurred . In addition , at the clinic each subject was asked what activities they had forgone in attending the clinic . Time was valued differently depending on whether work or leisure activities were forgone . The total private cost for each attender was calculated and comparison was made between attenders at hospital and at general practice . Results — A significantly greater proportion of subjects were accompanied when attending hospital than when attending general practitioner ( GP ) surgeries . Most attenders travelled by car , but the journey time was significantly longer for those visiting hospital . The expected total private cost associated with attendance for AAA screening was £ 5.47 . Attendance at GP surgeries had a lower private cost ( £ 4.21 ) than attendance at hospital ( £ 6.87 ) . Only 7·3 % of all men surveyed , and 6·5 % of all companions , would have been taking part in some form of paid occupation if they had not attended for screening . Conclusion — Despite the fact that most attenders for AAA screening will be retired , the associated private costs are appreciable and should be considered in assessing the economics of such screening programmes . The level of private costs varied depending on the location of screening : clinics held at GP practice s had lower private costs than those held at hospital 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 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 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 Macrolide treatment has been reported to lower the risk of recurrent ischaemic heart disease . The influence of macrolides on the expansion rate of abdominal aortic aneurysms ( AAAs ) remains unknown . The aim was to investigate the effect of roxithromycin on the expansion rate of small AAAs 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 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 INTRODUCTION Screening and observation of abdominal aortic aneurysms ( AAA ) produce psychological stress . Consequently , safe and optimal intervals of rescreening and observation must be developed . METHOD In a r and omised , mass screening trial of 6,339 men aged , 65 - 73 years from 1994 to 1998 , 76 % attended , and 191 ( 4 % ) had AAA > or = 3 cm . Twenty-four ( 0.5 % ) had AAA above 5 cm in diameter and were referred for surgery , while the rest were offered annual control . Later , all 348 ( 7.5 % ) men who , 3 to 5 years before , had had an ectatic aorta ( an infrarenal aortic diameter of 25 - 29 mm or a distal/renal aortic diameter ratio of > 1.2 ) were offered rescreening , together with a control group of 380 men . RESULTS None of the controls had developed AAA . Of those who initially had an aortic diameter of 25 - 29 mm aorta , 28.5 % had developed AAA ( size range 30 - 48 mm ) , whereas only 3.5 % with a ratio > 1.2 developed AAA ( size range 30 - 34 mm ) . During the fourth year of surveillance some AAA initially sized below 3.5 cm exp and ed to above 5 cm , whereas this occurred in some sized 3.5 - 3.9 cm during the second year and in most above 4 cm did during the first year of observation . CONCLUSION Rescreening for AAA can be restricted to initially ectatic aortas sized 25 - 29 mm at five-year intervals . Observation of small AAA can be restricted to 1 - 4 year intervals The prevalence of abdominal aortic aneurysm ( AAA ) in a community‐based sample of men and women aged 65–79 years was correlated with known risk factors . In addition , the effect of high blood pressure and the use of antihypertensive medication on growth of AAAs were studied Objectives To investigate the feasibility of selective screening for abdominal aortic aneurysm ( AAA ) based on identification of a target group of manageable size defined by risk factors for AAA . Setting Male residents of Perth , Western Australia , aged 65–83 years , who participated in a r and omised controlled trial of ultrasound screening for AAA . Methods Eligible men were identified from the electoral roll and invited to attend a screening clinic . Those who attended completed a question naire , had a limited physical examination , and underwent an ultrasound examination to identify the maximum diameter of the infrarenal aorta . Data on risk factors collected from the first 8995 men seen were used to calculate a multivariate risk score for the remaining 2755 men who were screened . Centiles of the risk score were used to define potential target groups for screening and the sensitivity and specificity of each of these selective screening strategies were calculated . We repeated the calculation separately for AAAs of at least 30 mm , 40 mm , and 50 mm in diameter . Results We found that screening half of the male population aged 65–83 years would find approximately 75 % of AAAs , regardless of their size , whereas screening only current smokers in this population would find approximately 20 % of AAAs . Conclusions Selective screening for AAA using easily recognisable risk factors is feasible but is not worthwhile as approximately 25 % of clinical ly significant cases would be missed 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 INTRODUCTION The hospital costs and benefits of screening older males for abdominal aortic aneurysms ( AAA ) are unknown . MATERIAL AND METHODS In 1994 , a hospital-based screening trial of 12,658 65 - 73-year-old males in the County of Viborg , Denmark , was started . AAA > 5 cm were referred for surgery . The remaining AAA were offered annual control scans . Those with aortic ectasia ( def . : 2.5 - 2.9 cm ) were rescreened at 5-year intervals . AAA-operations and deaths of AAA at hospital were registered . Finally , costs of screening , surveillance , and treatment were registered . Data on causes of death outside hospitals could not be obtained . RESULTS The attendance rate was 76 % , of whom 191 ( 4.0 % ) had AAA . The average observation time was 5.13 years . 60 in the screened and 41 in the control group were operated ( P = 0.06 ) , 7 and 27 were operated as an emergency ( P < 0.001 ) , and 6 and 19 died at the hospitals due to AAA ( p = 0.009 ) . The costs per scan were 83.50 DKK , 81,400 DKK per elective operation ( 71,485 DKK after screening ) , and 117,000 DKK for an emergency operation . The costs per prevented hospital death were 67,855 DKK or approx . 7,540 DKK per life year saved ( 1 GBP = 12 DKK ) . DISCUSSION Screening older males for AAA in Denmark seems very cost-effective and reduces hospital mortality of AAA by 68 % and probably the overall AAA-specific mortality by 73 % 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 The aim of the study was to analyse whether the selection and recruitment for hospital-based mass screening for abdominal aortic aneurysms ( AAA ) is acceptable for the population according to the criteria from the Council of Europe . METHODS A r and om sample of 4404 65 - 73-year-old males were invited to hospital-based mass screening for AAA . As methods of secondary recruitment , they could change their time of appointment , and non-responders were reinvited once . RESULTS The attendance rate was 76 per cent ; 4.2 per cent had AAA . Men with cardiopulmonary and vascular diseases had higher attendance rate ( 80.5 per cent ) , and prevalence of AAA ( 9.1 per cent ) . Men with potentially mobility-disabling diseases also had a higher attendance rate ( 80.4 per cent ) . However , possible unfavourable social selection was noticed in the group of retired men with no information of former occupation . They had 68.5 per cent attendance , and 7.6 per cent AAA . If true , this selection decreases the number of potentially diagnosed AAA by only 2 per cent . Opportunity of revised appointment and reinvitation of non-responders increased the primary attendance of 65 per cent to 76 per cent . More AAA were found at secondary scans ( 6.3 per cent compared with 3.9 per cent ) . CONCLUSION The attendance rate fell markedly with age , but the recruitment was high even at the age of 73 , and travel distance and social class did not markedly influence uptake . A positive morbidity selection to screening for AAA was observed for cardiovascular or pulmonary diseases and potentially mobility-disabling diseases . Furthermore , higher prevalence of AAA was found for initial nonattenders . Thus , screening for AAA seems acceptable to the population , and extra efforts to increase the attendance are beneficial without increased costs per diagnosed AAA . Finally , if mass-screening proves to be cost-ineffective , selective screening of patients with hypertension or ischaemic heart disease might be beneficial The incidence of abdominal aortic aneurysms ( AAA ) and ruptured AAA is increasing . One to three percent of deaths among 65 - 80 year-old males are caused by AAA . Sixty-six to ninety-five percent of ruptured AAA are lethal , while elective resection has a 3 - 6 % operative mortality . Most AAA 's are asymptomatic before rupture . Ultrasonographic scanning of the aorta takes below ten minutes with close to 100 % sensitivity and specificity . The County of Viborg has started a r and omized screening trial including 13,500 65 - 73 year-old males . Half of these are invited to the nearest hospital over a period of three years . In 1994 - 1995 4938 were invited and 3748 were scanned , result ing in an acceptance rate of 76 % . The aorta was visible in 99.7 % , and the total time consumption was 9.7 minutes per scan . The costs were 83.75 DKK per scan . One hundred and fifty-three ( 4.1 % ) had an AAA defined as an aortic diameter above 29 mm . Twenty were above 49 mm and were offered operation , i.e. 5.3 per thous and scans or 13 % of the diagnosed AAA The Multicentre Aneurysm Screening Study ( MASS ) provided strong evidence for both the clinical benefit and the cost‐effectiveness of a screening programme for abdominal aortic aneurysms ( AAAs ) in men . If a national screening programme for AAA were adopted in the UK , it would be expected to increase the elective and decrease the emergency surgical workload Abstract Objective To determine whether screening Danish men aged 65 or more for abdominal aortic aneurysms reduces mortality . Design Single centre r and omised controlled trial . Setting All five hospitals in Viborg County , Denmark . Participants All 12 639 men born during 1921 - 33 and living in Viborg County . In 1994 we included men born 1921 - 9 ( 64 - 73 years ) . We also included men who became 65 during 1995 - 8 . Interventions Men were r and omised to the intervention group ( screening by abdominal ultrasonography ) or control group . Participants with an abdominal aortic aneurysm > 5 cm were referred for surgical evaluation , and those with smaller aneurysms were offered annual scans . Outcome measures Specific mortality due to abdominal aortic aneurysm , overall mortality , and number of planned and emergency operations for abdominal aortic aneurysms . Results 4860 of 6333 men were screened ( attendance rate 76.6 % ) . 191 ( 4.0 % of those screened ) had abdominal aortic aneurysms . The mean follow-up time was 52 months . The screened group underwent 75 % ( 95 % confidence interval 51 % to 91 % ) fewer emergency operations than the control group . Deaths due to abdominal aortic aneurysms occurred in nine patients in the screened group and 27 in the control group . The number needed to screen to save one life was 352 . Specific mortality was significantly reduced by 67 % ( 29 % to 84 % ) . Mortality due to non-abdominal aortic aneurysms was non-significantly reduced by 8 % . The benefits of screening may increase with time . Conclusion Mass screening for abdominal aortic aneurysms in Danish men aged 65 or more reduces mortality 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 the incidence of asymptomatic abdominal aortic aneurysms and the implication s for an ultrasound screening programme in Engl and and Wales . Methods First screen data were obtained from the Chichester and Huntingdon screening studies and used to estimate the prevalence of abdominal aortic aneurysms . The incidence of new , asymptomatic aneurysms was estimated from the prevalence rates observed in the Huntingdon screening study . Setting Screening programmes in Huntingdon and Chichester using ultrasound to screen all men over the age of 50 and men over age 65 respectively . Results The prevalence of abdominal aortic aneurysms ranged between 5.32 % and 8.02 % and between 6.18 % and 9.88 % of men aged between 65 and 79 in Chichester and Huntingdon respectively . Annual incidence rates , estimated by age , rose steadily reaching a peak of 0.67 % of the Huntingdon population per year at age 65 . Thereafter incidence falls . Estimates of the incidence of new asymptomatic abdominal aortic aneurysms , based on the observed prevalence data , were calculated and showed a peak at age 65 . Conclusions Hypotheses are offered to explain this unexpected early peak in incidence . This information should allow the definition of the optimum age for screening , and the relative benefits of screening at different intervals if widespread screening is adopted in the future The cysteine protease inhibitor cystatin C may play a role in the development and progression of abdominal aortic aneurysms ( AAAs ) BACKGROUND Increased life expectancy in men during the last thirty years is largely due to the decrease in mortality from cardiovascular disease in the age group 29 - -69 yr . This change has result ed in a change in the disease profile of the population with conditions such as aneurysm of the abdominal aorta ( AAA ) becoming more prevalent . The advent of endoluminal treatment for AAA has encouraged prophylactic intervention and fueled the argument to screen for the disease . The feasibility of inserting an endoluminal graft is dependent on the morphology and growth characteristics of the aneurysm . This study used data from a r and omized controlled trial of ultrasound screening for AAA in men aged 65 - -83 yr in Western Australia for the purpose of determining the norms of the living anatomy in the pressurized infrarenal aorta . AIMS To examine ( 1 ) the diameters of the infra-renal aorta in aneurysmal and non-aneurysmal cases , ( 2 ) the implication s for treatment modalities , with particular reference to endoluminal grafting , which is most dependent on normal and aneurysmal morphology , and ( 3 ) any evidence to support the notion that northern Europeans are predisposed to aneurysmal disease . METHODS Using ultrasound , a r and omized control trial was established in Western Australia to assess the value of a screening program in males aged 65 - -83 yr . The infra-renal aorta was defined as aneurysmal if the maximum diameter was 30 mm or more . Aortic diameter was modelled both as a continuous ( in mm ) and as a binary outcome variable , for those men who had an infra-renal diameter of 30 mm or more . ANOVA and linear regression were used for modelling aortic diameter as a continuum , while chi-square analysis and logistic regression were used in comparing men with and without the diagnosis of AAA . FINDINGS By December 1998 , of 19,583 men had been invited to undergo ultrasound screening for AAA , 12,203 accepted the invitation ( corrected response fraction 70.8 % ) . The prevalence of AAA increased with age from 4.8 % at 65 yr to 10.8 % at 80 yr ( chi(2)=77.9 , df=3 , P<0.001 ) . The median ( IQR ) diameter for the non-aneurysmal group was 21.4 mm ( 3.3 mm ) and there was an increase ( chi(2)=76.0 , df=1 , P<0.001 ) in the diameter of the infra-renal aorta with age . Since 27 mm is the 95th centile for the non-aneurysmal infra-renal aorta , a diameter of 30 mm or more is justified as defining an aneurysm . The risk of AAA was higher in men of Australian ( OR=1.0 ) and northern European origin ( OR=1.0 , 95%CL : 0.9 , 1.2 ) compared with those of Mediterranean origin ( OR=0.5 , 95%CL : 0.4 , 0.7 ) . CONCLUSION Although screening has not yet been shown to reduce mortality from AAA , these population -based data assist the underst and ing of aneurysmal disease and the further development and use of endoluminal grafts for this condition Objective — To analyse the benefits of screening older men for abdominal aortic aneurysms . Methods — A hospital based screening trial concerning 13 500 65–73 year old men using B — mode ultrasonographic scanning . To improve the response rate the invited men could change their appointment , and non — responders were reinvited . Results — Results from the first year of the trial are presented . Among 4404 invited , 3344 ( 76 % ) were scanned . The primary response rate was 64.8 % , but a further 11.2 % were scanned after revised appointments or reinvitation . The whole infrarenal aorta could be visualised in 97.6 % , and the distal part in 99.7 % of the scans . The time taken for each scan was 9.7 minutes and the costs per scan were · 9.50 . One hundred and fifty three subjects ( 4.6 % ) had aortic diameters of 25.29 mm , and 141 ( 4.2 % ) had an abdominal aortic aneurysm , 19 ( 0.6 % ) above 49 mm in diameter . Conclusion — In Denmark the short term costs and benefits of screening older men for abdominal aortic aneurysms seem realistic . Long term costs and benefits need to be investigated 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 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 |
1,269 | 12,535,446 | No significant differences were detected between active intervention and control on the primary and secondary outcome measures reported in the studies .
There are no trials of other allergen reduction measures , such as pet washing or possibly pet removal | BACKGROUND Although pet removal has been recommended in guidelines on the management of allergic asthma , pet ownership remains high in families where one or more members have an allergy to pet d and er .
Allergen control measures such as air filtration units placed in the homes of pet-allergic asthmatics have been used as a means of reducing allergen exposure .
OBJECTIVES To determine the clinical efficacy of pet allergen control measures in the homes of people with pet-allergic asthma . | BACKGROUND Exposure to cat and dog allergens is very common in the Western World and is a serious cause of asthma in sensitized subjects . OBJECTIVE We sought to study the clinical effects of air cleaners in living rooms and bedrooms of asthmatic children sensitized to cat or dog allergens . METHODS Twenty asthmatic children sensitized to pet allergens ( cat/dog ) and with an animal at home participated in a double-blind , placebo-controlled , cross-over study in which the effects of air cleaners placed in the living room and bedroom for 3 months were compared with the effects of sham air cleaners . Before and after each study period , lung function , airway hyperresponsiveness ( adenosine monophosphate ) , and peak flow variation were recorded . Cat and dog allergen levels were assessed in the filters of the air cleaners . RESULTS After a 3-month intervention with active air cleaners , airway hyperresponsiveness decreased significantly , showing a 1.2 doubling dose increase of PC(20 ) adenosine ( P = .003 ) . Peak flow amplitude also decreased ( P = . 045 ) . Substantial amounts of airborne cat and dog allergen were captured by the air cleaners in living rooms and bedrooms as well . Allergen levels in floor dust were not changed . CONCLUSION In young asthmatic patients sensitized and exposed to pets in the home , application of air cleaners in living rooms and bedrooms was accompanied by a significant improvement in airway hyperresponsiveness and a decrease in peak flow amplitude The effects of supplementary computer instruction in house dust mite-avoidance measures on adherence to implementing measures , on home dust mite-allergen levels , and on symptomatology were investigated in 52 adult patients with mite-associated asthma . Twenty-six patients received conventional instruction ( counseling and written instruction ) and the other 26 patients received conventional plus 22 minutes of interactive computer-assisted instruction . Instructions were aim ed at mite-avoidance measures . Pre- and postinstruction dust sample s were collected , and adherence was monitored . All patients kept symptom diaries twice a day . Patients ' progress was followed for 12 weeks , and all patients completed the study . Adherence , number of observed and self-reported mite-avoidance measures implemented after visit , was higher for the computer group ( p = 0.023 ) . The computer-instructed group achieved significantly lower levels of mite allergen in bedroom carpets ( p = 0.004 ) with mean levels of mite allergen declining from 6.5 + /- 7.6 to 2.2 + /- 4.3 micrograms/gm of dust ( two-site monoclonal antibody assays ) , whereas levels for the conventional-instructed group did not change . Moreover , by study weeks 9 and 10 , the computer-instructed group was significantly less symptomatic ( p = 0.033 ) . Mean symptom scores for this group decreased from 12.4 to 7.7 , compared with 16.4 to 14.3 . Conventional instruction supplemented with computer instruction is suggested in mite education To evaluate the effect of a room high-efficiency particulate air ( HEPA ) cleaner on cat-induced asthma and rhinitis , 35 cat-allergic subjects who were living with one or more cats were studied in a double-blind , placebo controlled trial . After a 1 mo baseline period , subjects ' bedrooms were equipped with an active or placebo air cleaner for the following 3 mo . Evaluations included monthly measurement of cat-allergen levels , daily morning , afternoon , and nighttime nasal- and chest-symptom scores , twice-daily measurement of peak-flow rates , daily medication scores , monthly spirometry , and methacholine ( MCh ) challenge testing before and after the study . Airborne allergen levels were reduced in the active-filter group as compared with the placebo group ( p = 0.045 ) . However , no differences were detected in settled-dust allergen levels ( p = 0.485 ) , morning , afternoon , or nighttime nasal-symptom scores ( p = 0.769 , 0.534 , and 0.138 ) , chest-symptom scores ( p = 0.388 , 0.179 , and 0.215 ) , sleep disturbance ( p = 0.101 ) , morning or afternoon peak-flow rates ( p = 0 . 424 and 0.679 ) , or rescue medication use ( nasal , p = 0.164 , chest , p = 0.650 ) , respectively . Although the combination of a HEPA room air cleaner , mattress and pillow covers , and cat exclusion from the bedroom did reduce airborne cat-allergen levels , no effect on disease activity was detected for any parameter studied BACKGROUND In Atlanta , as in other major urban areas of the United States , asthma is a leading cause of school absenteeism , emergency department use , and hospitalization . Recent guidelines for asthma management recommend reducing exposure to relevant allergens , but neither the feasibility nor the efficacy of this form of treatment has been established for children living in poverty . OBJECTIVE We sought to investigate allergen avoidance as a treatment for asthma among inner-city children . METHODS One hundred four children with asthma living in the city of Atlanta were enrolled into a controlled trial of avoidance without being skin tested . The children were r and omized to an active avoidance group , a placebo avoidance group , and a second control group for which no house visits occurred until the end of the first year . Avoidance included bed and pillow covers , hot washing of bedding , and cockroach bait . Eighty-five children completed the study , and the outcome was measured as unscheduled clinic visits , emergency department visits , and hospitalization for asthma , as well as changes in mite and cockroach allergen levels . RESULTS There was a significant decrease in acute visits for asthma among children whose homes were visited ( P < .001 ) . However , there was no significant difference between the active and placebo homes either in the effect on asthma visits or in allergen concentrations . When the children with mite allergy were considered separately , there was a significant correlation between decreased mite allergen and change in acute visits ( P < .01 ) . The avoidance measures for cockroach allergen appeared to be ineffective , and the changes observed did not correlate with changes in visits . CONCLUSIONS Applying allergen avoidance as a treatment for asthma among children living in poverty is difficult because of multiple sensitivities and problems applying the protocol s in this environment . The current results demonstrate that home visiting positively influences the management of asthma among families living in poverty . Furthermore , the results for children with mite allergy strongly suggest that decreasing relevant allergen exposure should be an objective of treatment in this population This study was design ed to assess the effectiveness of a high-efficiency particulate air ( HEPA ) filter in alleviating allergic respiratory symptoms . Thirty-two patients were studied who had symptomatic perennial rhinitis and /or asthma during the fall and winter months and had a positive skin test with house dust or house dust -- mite extract . An ENVIRACAIRE room air cleaner was placed in the bedroom for 8 weeks . In a r and om manner , the active filter was used for 4 weeks and a blank filter for 4 weeks . There was an average 70 % reduction in the particulate matter greater than or equal to 0.3 micron with the HEPA filter . In a double-blind design , results were assessed by analysis of the patients ' symptom/medication scores and subjective evaluation . For the total study , there was no difference in the total symptom/medication scores or individual symptom scores during the placebo and active-filter periods . Analysis of the last 2 weeks of each filter period in which respiratory infection was absent demonstrated definite differences in total and individual symptoms , suggesting active-filter benefit . Patients ' subjective responses also suggested benefit from the filter . The overall impression is that the HEPA filter can reduce allergic respiratory symptoms Recommendations for allergen avoidance or allergen reduction measures play an important part in the treatment of allergic asthmatic patients . The purpose of this study was to test recently developed air-cleaners with respect to their capacity to capture airborne allergen particles and to improve clinical parameters of asthmatic patients sensitized to aeroallergens . Forty five allergic asthmatic patients were studied in a double-blind procedure for 6 months . The patients were divided into three groups of 15 patients . In Group 1 , the intervention consisted of the application of active air-cleaners in living-rooms and bedrooms . In Group 2 , placebo air-cleaners were used in combination with allergen-impermeable mattress covers . In Group 3 , the same intervention was performed as in Group 2 but with active air-cleaners . Allergen levels in mattress and floor dust were measured before , and 3 and 6 months after the interventions . After 6 months , the air-cleaners were dismantled and the filters were analysed for the amount of dust collected and allergen content . Immunological and lung function parameters were measured before , and 3 and 6 months after the interventions . Considerable amounts of airborne dust and allergenic particles were captured in the filters of the air-cleaners . Up to the 18.9 g of dust , 4,513 ng of house dust mite allergen , Der p 1 , and 50,000 mU of cat allergen , Fel d 1 , ( in houses with cats ) were collected by air-cleaners in living-rooms . Only in Group 3 ( in which both active air-cleaners and mattress covers were used ) was a small ( less than 1 doubling dose ) but statistically significant improvement of provocative concentration of histamine causing a 20 % fall in forced expiratory volume in one second ( PC20 ) observed ( from 5.96 to 9.02 mg x mL(-1 ) ) . The amount of dust and house dust mite allergen collected in the filters was significantly correlated with an improvement of peak flow variation . In combination with other allergen avoidance measures , the examined air-cleaners can contribute to diminished allergen exposure and improvement of airway hyperresponsiveness in asthmatic patients A new , portable laminar air-flow filter ( Enviracaire ) was tested on 13 asthmatic children , using a double-blind single crossover study . There was a statistical improvement in symptom scores during filter use ; however , peak flows did not improve significantly . The authors feel this method of avoiding indoor airborne irritants is useful and warrants further study The efficacy of an air‐cleaning device equipped with a high efficiency particulate air ( HEPA ) filter ( without further avoidance measures ) was studied in patients allergic to house dust mite . The effects of the air‐cleaner on indoor Dermatophagoides sp. levels , symptom score and bronchial hyperresponsiveness in nine mite‐allergic patients were assessed using a cross‐over controlled study . No significant effect was demonstrated on indoor Dermatophagoides sp. levels when comparing the period of air‐cleaner activity ( 2 months ) with the control period ( 2 months ) . The Dermatophagoides sp. levels in the houses studied were lower than the risk level for asthmatic attacks , making it difficult to assess any effect on asthma ; however , neither bronchial hyperresponsiveness nor rhinitis symptom score were changed by air‐cleaner activity . During the trial period , however the mean level of Dermatophagoides sp. allergen in the houses changed spontaneously from 4.4 Hg/g ( mean level in the first 2 trial months ) to 1 . 75 μg/g of dust ( second 2 months ) ( P < 0.05 ) . Owing to this change , the mean rhinitis symptom score also decreased ( P < 0.05 ) , even if no significant correlation was demonstrated ( r = 0.4 P= 0.089 ) . HEPA filter air‐cleaners appear insufficient as substitutes for st and ard avoidance measures in mite allergic patients |
1,270 | 25,550,671 | Based on the findings of this systematic review there is no conclusive evidence that clearly favours spinal manipulation or exercise as more effective in treatment of CLBP . | BACKGROUND CONTEXT Chronic low back pain ( CLBP ) is a prevalent disorder that has a significant burden to society in terms of loss of work time and increased economic cost .
Two common treatment choices of intervention for CLBP are spinal manipulation and prescribed exercise .
PURPOSE The purpose of this systematic review was to examine the effectiveness of spinal manipulation vs prescribed exercise for patients diagnosed with CLBP .
Studies that compared head-to-head spinal manipulation to an exercise group were included in this review . | Study Design . A prospect i ve r and omized controlled trial . Objectives . To examine the effectiveness of combined manipulative treatment , stabilizing exercises , and physician consultation compared with physician consultation alone for chronic low back pain . Summary of Background Data . Strong evidence exists that manual therapy provides more effective short-term pain relief than does placebo treatment in the management of chronic low back pain . The evidence for long-term effect is lacking . Methods . Two hundred four chronic low back pain patients , whose Oswestry disability index was at least 16 % , were r and omly assigned to either a manipulative-treatment group or a consultation group . All were clinical ly examined , informed about their back pain , provided with an educational booklet , and were given specific instructions based on the clinical evaluation . The treatment included four sessions of manipulation and stabilizing exercises aim ing to correct the lumbopelvic rhythm . Question naires inquired about pain intensity , self-rated disability , mental depression , health-related quality of life , health care costs , and production costs . Results . At the baseline , the groups were comparable , except for the percentage of employees ( P = 0.01 ) . At the 5- and 12-month follow-ups , the manipulative-treatment group showed more significant reductions in pain intensity ( P < 0.001 ) and in self-rated disability ( P = 0.002 ) than the consultation group . However , we detected no significant difference between the groups in health-related quality of life or in costs . Conclusions . The manipulative treatment with stabilizing exercises was more effective in reducing pain intensity and disability than the physician consultation alone . The present study showed that short , specific treatment programs with proper patient information may alter the course of chronic low back pain Objective : This article examines the effectiveness of manual therapy with specific adjuvant exercise for treating chronic low back pain and disability . Methods : A single blind , r and omized , controlled trial was employed . Patients were prescribed an exercise program that was tailored to treat their musculoskeletal dysfunctions or given a nonspecific program of general stretching and aerobic conditioning . In addition , patients received manual therapy or sham manual therapy . Participants were seen for 6 weekly sessions and were asked to perform their exercise program twice daily . Results : Seventy-two out of 100 patients completed the study . Multivariate tests conducted for measures of pain and disability revealed a significant group by time interaction ( P = 0.04 and P = 0.05 , respectively ) , indicating differential change in these measures pretreatment to posttreatment as a function of the treatment received . When controlling for pretreatment scores , patients receiving manual therapy with specific adjuvant exercise reported significant reductions in pain . No change in perceived disability was observed , with the exception that patients receiving sham manual therapy with specific adjuvant exercise reported significantly greater disability at posttreatment . Discussion : Manual therapy with specific adjuvant exercise appears to be beneficial in treating chronic low back pain . Despite changes in pain , perceived function did not improve . It is possible that impacting chronic low back pain alone does not address psychosocial or other factors that may contribute to disability . Further studies are needed to examine the long-term effects of these interventions and to address what adjuncts are beneficial in improving function in this population Abstract Practice guidelines recommend various types of exercise and manipulative therapy for chronic back pain but there have been few head‐to‐head comparisons of these interventions . We conducted a r and omized controlled trial to compare effects of general exercise , motor control exercise and manipulative therapy on function and perceived effect of intervention in patients with chronic back pain . Two hundred and forty adults with non‐specific low back pain ⩾3 months were allocated to groups that received 8 weeks of general exercise , motor control exercise or spinal manipulative therapy . General exercise included strengthening , stretching and aerobic exercises . Motor control exercise involved retraining specific trunk muscles using ultrasound feedback . Spinal manipulative therapy included joint mobilization and manipulation . Primary outcomes were patient‐specific function ( PSFS , 3–30 ) and global perceived effect ( GPE , −5 to 5 ) at 8 weeks . These outcomes were also measured at 6 and 12 months . Follow‐up was 93 % at 8 weeks and 88 % at 6 and 12 months . The motor control exercise group had slightly better outcomes than the general exercise group at 8 weeks ( between‐group difference : PSFS 2.9 , 95 % CI : 0.9–4.8 ; GPE 1.7 , 95 % CI : 0.9–2.4 ) , as did the spinal manipulative therapy group ( PSFS 2.3 , 95 % CI : 0.4–4.2 ; GPE 1.2 , 95 % CI : 0.4–2.0 ) . The groups had similar outcomes at 6 and 12 months . Motor control exercise and spinal manipulative therapy produce slightly better short‐term function and perceptions of effect than general exercise , but not better medium or long‐term effects , in patients with chronic non‐specific back pain BACKGROUND CONTEXT Several conservative therapies have been shown to be beneficial in the treatment of chronic low back pain ( CLBP ) , including different forms of exercise and spinal manipulative therapy ( SMT ) . The efficacy of less time-consuming and less costly self-care interventions , for example , home exercise , remains inconclusive in CLBP population s. PURPOSE The purpose of this study was to assess the relative efficacy of supervised exercise , spinal manipulation , and home exercise for the treatment of CLBP . STUDY DESIGN / SETTING An observer-blinded and mixed- method r and omized clinical trial conducted in a university research clinic in Bloomington , MN , USA . PATIENT SAMPLE Individuals , 18 to 65 years of age , who had a primary complaint of mechanical LBP of at least 6-week duration with or without radiating pain to the lower extremity were included in this trial . OUTCOME MEASURES Patient-rated outcomes were pain , disability , general health status , medication use , global improvement , and satisfaction . Trunk muscle endurance and strength were assessed by blinded examiners , and qualitative interviews were performed at the end of the 12-week treatment phase . METHODS This prospect i ve r and omized clinical trial examined the short- ( 12 weeks ) and long-term ( 52 weeks ) relative efficacy of high-dose , supervised low-tech trunk exercise , chiropractic SMT , and a short course of home exercise and self-care advice for the treatment of LBP of at least 6-week duration . The study was approved by local institutional review boards . RESULTS A total of 301 individuals were included in this trial . For all three treatment groups , outcomes improved during the 12 weeks of treatment . Those who received supervised trunk exercise were most satisfied with care and experienced the greatest gains in trunk muscle endurance and strength , but they did not significantly differ from those receiving chiropractic spinal manipulation or home exercise in terms of pain and other patient-rated individual outcomes , in both the short- and long-term . CONCLUSIONS For CLBP , supervised exercise was significantly better than chiropractic spinal manipulation and home exercise in terms of satisfaction with treatment and trunk muscle endurance and strength . Although the short- and long-term differences between groups in patient-rated pain , disability , improvement , general health status , and medication use consistently favored the supervised exercise group , the differences were relatively small and not statistically significant for these individual outcomes Study Design . R and omized , single blind , controlled trial . Objective . To determine the efficacy of 2 components of musculoskeletal physiotherapy on chronic low back disorder . Summary of Background Data . Musculoskeletal physiotherapy encompasses many treatment methods , however , manual therapy and exercises to rehabilitate spinal stabilization are the most frequently used . Despite their popularity , scant evidence supports their use on subjects with chronic low back disorder . Methods . A total of 346 subjects were r and omized to manual therapy , a 10-week spinal stabilization rehabilitation program , or a minimal intervention control group . Data were collected at baseline , and 3 , 6 , 12 , and 24 months after intervention . Outcome measures recorded intensity of low back pain , disability , h and icap , medication , and quality of life . There were 4 main variables combined in a primary component analysis to form a single outcome measure ( i.e. , a measure of dysfunction ) . Results . The results indicated statistically significant improvements in favor of the spinal stabilization group at the 6-month stage in pain ( 65.9 % reduction in symptoms ) and dysfunction ( combined mean reduction of 134 , st and ard error 23.84 ) , and at the 1-year stage in medication ( 34.3 % reduction in medication ) , dysfunction ( combined mean reduction of 134 , st and ard error 18.2 ) , and disability ( mean difference in change 15.71 Oswestry Disability Index , 95 % confidence interval 19.3–10.01 ) . Conclusions . As a component of musculoskeletal physiotherapy , the spinal stabilization program is more effective than manually applied therapy or an education booklet in treating chronic low back disorder over time . Both manual therapy and the spinal stabilization program are significantly effective in pain reduction in comparison to an active control . To our knowledge and up until now , this result has not been shown in patients with chronic low back disorder Background Recent clinical recommendations still propose active exercises ( AE ) for CNSLBP . However , acceptance of exercises by patients may be limited by pain-related manifestations . Current evidence s suggest that manual therapy ( MT ) induces an immediate analgesic effect through neurophysiologic mechanisms at peripheral , spinal and cortical levels . The aim of this pilot study was first , to assess whether MT has an immediate analgesic effect , and second , to compare the lasting effect on functional disability of MT plus AE to sham therapy ( ST ) plus AE . Methods Forty-two CNSLBP patients without co-morbidities , r and omly distributed into 2 treatment groups , received either spinal manipulation/mobilization ( first intervention ) plus AE ( MT group ; n = 22 ) , or detuned ultrasound ( first intervention ) plus AE ( ST group ; n = 20 ) . Eight therapeutic sessions were delivered over 4 to 8 weeks . Immediate analgesic effect was obtained by measuring pain intensity ( Visual Analogue Scale ) before and immediately after the first intervention of each therapeutic session . Pain intensity , disability ( Oswestry Disability Index ) , fear-avoidance beliefs ( Fear-Avoidance Beliefs Question naire ) , erector spinae and abdominal muscles endurance ( Sorensen and Shirado tests ) were assessed before treatment , after the 8th therapeutic session , and at 3- and 6-month follow-ups . Results Thirty-seven subjects completed the study . MT intervention induced a better immediate analgesic effect that was independent from the therapeutic session ( VAS mean difference between interventions : -0.8 ; 95 % CI : -1.2 to −0.3 ) . Independently from time after treatment , MT + AE induced lower disability ( ODI mean group difference : -7.1 ; 95 % CI : -12.8 to −1.5 ) and a trend to lower pain ( VAS mean group difference : -1.2 ; 95 % CI : -2.4 to −0.30 ) . Six months after treatment , Shirado test was better for the ST group ( Shirado mean group difference : -61.6 ; 95 % CI : -117.5 to −5.7 ) . Insufficient evidence for group differences was found in remaining outcomes . Conclusions This study confirmed the immediate analgesic effect of MT over ST . Followed by specific active exercises , it reduces significantly functional disability and tends to induce a larger decrease in pain intensity , compared to a control group . These results confirm the clinical relevance of MT as an appropriate treatment for CNSLBP . Its neurophysiologic mechanisms at cortical level should be investigated more thoroughly . Trial registration Trial registration number : OBJECTIVE To study the efficacy of manual therapy and physiotherapy in subgroups of patients with persistent back and neck complaints . The second objective was to determine the correlation between three important outcome measures used in this trial . DESIGN R and omized clinical trial ( subgroup analysis ) . SETTING Primary health care in the Netherl and s. PATIENTS Two hundred fifty-six patients with nonspecific back and neck complaints of at least 6 wk duration who had not received physiotherapy or manual therapy in the past 2 yr . INTERVENTIONS At the discretion of the manual therapists , physiotherapists and general practitioners . Physiotherapy consisted of exercises , massage and physical therapy ( heat , electrotherapy , ultrasound , shortwave diathermy ) . Manual therapy consisted of manipulation and mobilization of the spine . Treatment by the general practitioner consisted of drugs ( e.g. , analgesics ) , advice about posture , home exercises and (bed)rest . Placebo treatment consisted of detuned shortwave diathermy ( 10 min ) and detuned ultrasound ( 10 min ) . MAIN OUTCOME MEASURES Changes in severity of the main complaint and limitation of physical functioning measured on 10-point scales by a blinded research assistant and global perceived effect measured on a 6-point scale by the patients . RESULTS Improvement in the main complaint was larger with manual therapy ( 4.3 ) than with physiotherapy ( 2.5 ) for patients with chronic conditions ( duration complaint of 1 yr or longer ) . Also , improvement in the main complaint was larger with manual therapy ( 5.5 ) than with physiotherapy ( 4.0 ) for patients younger than 40 yr ( both were measured after 12-mo follow-up ) . Labeling of patients by the treating manual therapists as " suitable " or " not suitable " for treatment with manual therapy did not predict differences in outcomes . Generally , there was a moderate to strong correlation between the three outcome measures , although a considerable number of patients gave a relatively low score for perceived benefit , while the research assistant gave a high improvement score for the main complaint and physical functioning . CONCLUSIONS The subgroup analysis suggests better results of manual therapy compared to physiotherapy in chronic patients ( duration of present complaints of 1 yr or longer ) and in patients younger than 40 yr old ) . Differences for other subgroups were less clear . The explorative findings of these subgroup analyses have to be investigated in future research 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 . Study Design . A prospect i ve , cohort study of patients with nonradicular low back pain referred to physical therapy . Objective . Develop a clinical prediction rule for identifying patients with low back pain who improve with spinal manipulation . Summary of Background Data . Development of clinical prediction rules for classifying patients with low back pain who are likely to respond to a particular intervention , such as manipulation , would improve clinical decision-making and research . Methods . Patients with nonradicular low back pain underwent a st and ardized examination and then underwent a st and ardized spinal manipulation treatment program . Success with treatment was determined using percent change in disability scores over three sessions and served as the reference st and ard for determining the accuracy of examination variables . Examination variables were first analyzed for univariate accuracy in predicting success and then combined into a multivariate clinical prediction rule . Results . Seventy-one patients participated . Thirty-two had success with the manipulation intervention . A clinical prediction rule with five variables ( symptom duration , fear – avoidance beliefs , lumbar hypomobility , hip internal rotation range of motion , and no symptoms distal to the knee ) was identified . The presence of four of five of these variables ( positive likelihood ratio = 24.38 ) increased the probability of success with manipulation from 45 % to 95 % . Conclusion . It appears that patients with low back pain likely to respond to manipulation can be accurately identified before treatment Objective : To compare spinal manipulation , back school and individual physiotherapy in the treatment of chronic low back pain . Design : R and omized trial , 12-month follow-up . Setting : Outpatient rehabilitation department . Participants : 210 patients with chronic , non-specific low back pain , 140/210 women , age 59 ± 14 years . Interventions : Back school and individual physiotherapy scheduled 15 1-hour-sessions for 3 weeks . Back school included : group exercise , education/ ergonomics ; individual physiotherapy : exercise , passive mobilization and soft-tissue treatment . Spinal manipulation , given according to Manual Medicine , scheduled 4 to 6 20’-sessions once-a-week . Outcome : Rol and Morris Disability Question naire ( scoring 0 - 24 ) and Pain Rating Scale ( scoring 0 - 6 ) were assessed at baseline , discharge 3 , 6 , and 12 months . Results : 205 patients completed the study . At discharge , disability score decreased by 3.7 ± 4.1 for back school , 4.4 ± 3.7 for individual physiotherapy , 6.7 ± 3.9 for manipulation ; pain score reduction was 0.9 ± 1.1 , 1.1 ± 1.0 , 1.0 ± 1.1 , respectively . At 12 months , disability score reduction was 4.2 ± 4.8 for back school , 4.0 ± 5.1 for individual physiotherapy , 5.9 ± 4.6 for manipulation ; pain score reduction was 0.7 ± 1.2 , 0.4 ± 1.3 , and 1.5 ± 1.1 , respectively . Spinal manipulation was associated with higher functional improvement and long-term pain relief than back school or individual physiotherapy , but received more further treatment at follow-ups ( P<0.001 ) ; pain recurrences and drug intake were also reduced compared to back school ( P < 0.05 ) or individual physiotherapy ( P < 0.001 ) . Conclusions : Spinal manipulation provided better short and long-term functional improvement , and more pain relief in the follow-up than either back school or individual physiotherapy BACKGROUND Recent studies on chronic low back pain ( cLBP ) rehabilitation suggest that predictors of treatment outcome may be differ according to the considered conservative treatment . AIM To identify predictors of response to back school ( BS ) , individual physiotherapy ( IP ) or spinal manipulation ( SM ) for cLBP . POPULATION out patients with cLBP . SETTING Outpatient rehabilitation department . DESIGN Retrospective analysis from a r and omized trial . METHODS Two hundred and ten patients with cLBP were r and omly assigned to either BS , IP or SM ; the Rol and Morris Disability Question naire ( RM ) was assessed before and after treatment : those who decreased their RM score < 2.5 were considered non-responders . Baseline potential predictors of outcome included demographics , general and cLBP history , life satisfaction . RESULTS Of the 205 patients who completed treatment ( 140/205 women , age 58 + 14 years ) , non-responders were 72 ( 34.2 % ) . SM showed the highest functional improvement and the lowest non-response rate . In a multivariable logistic regression , lower baseline RM score ( OR 0.82 , 95 % CI 0.76 - 0.89 , P<0.001 ) and received treatment ( OR 0.32 , 95 % CI 0.21 - 0.50 , P<0.001 ) were independent predictors of non-response . Being in the lowest tertile of baseline RM score ( < 6 ) predicted non response to treatment for BS and IP , but not for SM ( same risk for all tertiles ) . CONCLUSIONS In our patients with cLBP lower baseline pain-related disability predicted non-response to physiotherapy , but not to spinal manipulation . CLINICAL REHABILITATION IMPACT Our results suggest that , independent form other characteristics , patients with cLBP and low pain-related disability should first consider spinal manipulation as a conservative treatment Objectives : The aim of this study on persons with nonspecific chronic low back pain was to evaluate the effect of a multimodal physical therapy program with or without the addition of deep-water running on pain , physical disability , and general health . Design : A r and omized controlled trial involving 46 subjects with nonspecific chronic low back pain were treated three times a week for 15 wks . Each group received 60 mins of multimodal physical therapy program ( an individualized exercise program ; manual therapy ; and back care , pain education , and information on an active lifestyle ) , whereas one group performed additional 20-min sessions of deep-water running at an individual workload of the aerobic threshold . Results : Both interventions result ed in significant improvements in pain , disability , and physical health . The mean change in pain , disability , and physical health state were −36.1 ± 25.1 mm on the visual analog scale , −3.0 ± 4.8 points for the Rol and Morris Question naire , and 10.6 ± 12.9 points for the Short Form-12 for the physical therapy plus deep-water running group and −34.1 ± 26.0 mm on the visual analog scale , −1.6 ± 1.5 points for the Rol and Morris Question naire , and 8.9 ± 13.0 points for the Short Form-12 for the physical therapy alone group . Conclusions : Pain , disability , health status , muscle strength and endurance , and lumbar range of motion significantly improved in both groups . The addition of a deep-water running program at an individual workload of the aerobic threshold to the multimodal physical therapy program produced a significant improvement in pain in patients with nonspecific chronic low back pain , but this was not significantly different when compared with multimodal physical therapy program alone . Disability , health status , muscle strength and endurance , and lumbar range of motion significantly improved to a similar level in both intervention groups Study Design . A r and omized clinical trial with blinded assessment . Objectives . To investigate the clinical efficacy of 2 active interventions for patients with chronic low back pain . Summary of Background Data . Manual therapy and exercise prescription are treatments frequently prescribed for patients with chronic low back pain . The evidence for the relative benefit of these treatments is limited , and questions concerning the most appropriate type of intervention remain unanswered . Methods . Eighty patients with chronic low back pain ( > 3 months ) were r and omized to one of the following treatments , involving 8 treatments over 8 weeks ; 1 ) one-to-one treatment involving 30 minutes of manual therapy ( mobilizations to the spine ) and spinal stabilization exercises , and 2 ) a 10 station exercise class involving aerobic exercises , spinal stabilization exercises , and manual therapy . Three physiotherapists led the hour long group with a maximum of 10 patients . Question naires were completed , and physical measurements were taken by a blinded observer before r and omization , at the completion of treatment , and at 6 months and 12 months after the completion of treatment . The intention-to-treat principle was used in data analysis . Results . Eleven patients dropped out of the individual treatment sessions and 7 dropped out of the exercise group . There was a significant reduction ( reduced disability ) in the question naire score in both groups , and there were significant increases in range for all the physical movements tested in both groups . The exercise group was 40 % more cost effective than the individual treatments . Conclusion . Both forms of intervention were associated with significant improvement . On-going clinical research is necessary to provide guidance as to the clinical efficacy of various forms of intervention The present aim was to compare the effects of stabilizing training with those of manual treatment in patients with sub-acute or chronic low-back pain ( LBP ) . Forty-seven patients were r and omized to a stabilizing training group ( ST group ) or a manual treatment group ( MT group ) . The patients underwent a 6-week treatment programme on a weekly basis . Pain , health and functional disability level at the start of treatment , after treatment , and at 3- and 12-month follow-ups were assessed . In the ST group all assessed variables improved significantly ( P<0.05 ) after the treatment period and were maintained long term . After the treatment period there was a significant difference between the groups in assessed function ( P<0.05 ) . More individuals in the ST group had improved than in the MT group . At the 3-month follow-up significantly more improved individuals were evident in the ST group regarding pain , general health and functional disability levels . In the long term , significantly more ( P<0.05 ) patients in the MT group reported recurrent treatment periods . The study did not indicate any clear short-term differences between the groups in the accessed outcome measures . In the long term , however , stabilizing training seemed to be more effective than manual treatment in terms of improvement of individuals and the reduced need for recurrent treatment periods Study Design . A multicenter , r and omized , controlled trial with 1-year follow-up . Objectives . To compare the effect of manual therapy to exercise therapy in sick-listed patients with chronic low back pain ( > 8 wks ) . Summary and Background Data . The effect of exercise therapy and manual therapy on chronic low back pain with respect to pain , function , and sick leave have been investigated in a number of studies . The results are , however , conflicting . Methods . Patients with chronic low back pain or radicular pain sick-listed for more than 8 weeks and less than 6 months were included . A total of 49 patients were r and omized to either manual therapy ( n = 27 ) or to exercise therapy ( n = 22 ) . Sixteen treatments were given over the course of 2 months . Pain intensity , functional disability ( Oswestry disability index ) , general health ( Dartmouth COOP function charts ) , and return to work were recorded before , immediately after , at 4 weeks , 6 months , and 12 months after the treatment period . Spinal range of motion ( Schober test ) was measured before and immediately after the treatment period only . Results . Although significant improvements were observed in both groups , the manual therapy group showed significantly larger improvements than the exercise therapy group on all outcome variables throughout the entire experimental period . Immediately after the 2-month treatment period , 67 % in the manual therapy and 27 % in the exercise therapy group had returned to work ( P < 0.01 ) , a relative difference that was maintained throughout the follow-up period . Conclusions . Improvements were found in both intervention groups , but manual therapy showed significantly greater improvement than exercise therapy in patients with chronic low back pain . The effects were reflected on all outcome measures , both on short and long-term follow-up Question : What are the short- and long-term effects of spinal manipulation in patients with chronic low back pain ? Design : R and omised controlled trial . Setting : Outpatient physiotherapy department in UK . Participants : 120 people , aged 18–55 , with non-specific low back pain of greater than 3 months duration . Participants were excluded if they had a history of prior treatment including manipulation , chiropractic , osteopathy , and ultrasound , or were receiving disability benefit as a result of LBP . Interventions : Both groups were given a written set of exercises , chosen by the physiotherapist for each individual . In addition , one group received high velocity thrust manipulation in side-lying ( on average four sessions ) and the other group received therapeutic ultrasound ( 1 MHz , continuous pattern , on average six sessions ) . Outcomes : Pain intensity ( measured on a visual analogue scale , 0–100 mm ) , functional disability ( Oswestry question naire , 0–100 % ) , lumbar movements ( modified Schober ’s test ) , and muscle endurance ( measured by surface electromyography ) were measured before treatment , at the end of treatment program , and 6 months after r and omisation . Results : Participants in the manipulation/exercise group demonstrated a significantly greater reduction in pain intensity ( mean between-group difference 16.4 , 95 % CI 6.1 to 26.8 ) and functional disability ( mean-between group difference 7.8 , 95 % CI 2.4 to 13.2 ) , as well as improved lumbar flexion ( mean between-group difference 9.4 mm , 95 % CI 5.5 to 13.4 ) and extension ( mean between-group difference 3.4 mm , 95 % CI 1.0 to 5.8 ( p < 0.01 in all instances ) . After six months the manipulation/ exercise group still demonstrated greater benefit than those in the ultrasound/exercise group for pain ( mean betweengroup difference 15.1 , 95 % CI 7.55 to 22.64 ) and disability ( mean between-group difference 5.2 , 95 % CI 2.63 to 7.81 ) . Data for Month 6 are provided by the author because numbers reported in Table 3 in the published paper are incorrect . Conclusion : Manipulation and exercise showed greater improvement compared to ultrasound and exercise for participants with chronic low back pain , both at the end of treatment and at six months follow-up |
1,271 | 26,626,072 | This systematic review found that tendinopathy is present in children and adolescents , and increases in prevalence with age up to 18 years .
Male sex is significantly associated with tendinopathy in studies that report tendinopathy by tendon | Background Tendon pathology and tendinopathy have been reported in children and adolescents ; however , the age at onset and prevalence of the conditions have not been examined systematic ally .
Objective To examine the prevalence of lower limb tendon pathology and tendinopathy in children and adolescents , and the factors associated with these conditions in this population .
Conclusions The age at onset of lower limb tendinopathy in children and adolescents has not been widely studied . | Background Home and supervised exercise programmes consisting of stretching and eccentric exercises have been recommended for the management of lateral elbow tendinopathy ( LET ) . No studies have examined their comparative efficacy effectiveness . Objective In this study , whether a home exercise programme is more successful than a supervised exercise programme in treating patients with LET was investigated . Methods Patients with unilateral LET for at least 4 weeks were included in this trial . They were sequentially allocated to receive either a home exercise programme or a supervised exercise programme five times a week for 12 weeks . The exercise programme consisted of slow progressive eccentric exercises of wrist extensors and static stretching of the extensor carpi radialis brevis tendon . Outcome measures were pain , using a visual analogue scale , and function , using a visual analogue scale and the pain-free grip strength . Patients were evaluated at baseline , at the end of treatment ( week 12 ) , and 3 months ( week 24 ) after the end of treatment . Results 70 patients met the inclusion criteria . At the end of treatment , there was a decline in pain and a rise in function in both groups compared with baseline ( p<0.0005 , paired t test ) . There were significant differences in the reduction of pain and the improvement of function between the groups at the end of treatment and at the 3-month follow up ; the supervised exercise programme produced the largest effect ( p<0.0005 , independent t test ) . Conclusions Supervised exercise programme is superior to home exercise programme to reduce pain and improve function in patients with LET at the end of the treatment and at the follow-up . Further research is needed to confirm our results Tendons adapt in response to sports-specific loading , but sometimes develop tendinopathy . If the presence of ultrasound changes like hypoechoic areas and neovascularization in asymptomatic tendons precede ( and predict ) future tendon problems is unknown . The aim of this prospect i ve cohort study was to investigate the relationship between the development of ultrasound changes in the patellar and quadriceps tendons and symptoms of jumper 's knee , as well to examine the medium-term effects of intensive training on tendon thickness among adolescent athletes . Elite junior volleyball athletes were followed with semi-annual ultrasound and clinical examinations ( average follow-up : 1.7 years ) . Of the 141 asymptomatic athletes included , 22 athletes ( 35 patellar tendons ) developed jumper 's knee . In a multivariate logistic regression analysis , a baseline finding of a hypoechoic tendon area ( odds ratio 3.3 , 95 % confidence interval 1.1 to 9.2 ) increased the risk of developing symptoms of jumper 's knee . Patellar tendon thickness among healthy athletes did not change ( Wilk 's lambda , P = 0.07 ) while quadriceps tendon thickness increased ( P = 0.001 ) . In conclusion , ultrasound changes at baseline were risk factors for developing symptoms of jumper 's knee . Also , among healthy athletes , we observed a 7 - 11 % increase in quadriceps tendon thickness , while there was no increase in patellar tendon thickness Background : Jumper ’s knee is a common and troublesome condition among senior volleyball players , but its prevalence among elite junior players compared to matched non-sports active controls is not known . Objective : To clinical ly , and by sonography , examine the patellar tendons in elite junior volleyball players ( 15–19 years ) at the Swedish National Centre for volleyball and in matched controls . Methods : The patellar tendons in the 57 students at the Swedish National Centre for high school volleyball and in 55 age , height , and weight matched not regularly sports active controls were evaluated clinical ly and by grey scale ultrasonography ( US ) and power Doppler ( PD ) sonography . Results : There were no significant differences in mean age , height , and weight between the volleyball players and the controls . In the volleyball group , jumper ’s knee was diagnosed clinical ly and by US in 12 patellar tendons ( 10 male and two female ) . In 12/12 tendons , PD sonography demonstrated a neovascularisation in the area with structural tendon changes . In another 10 pain free tendons , there were structural tendon changes and neovessels . In the control group , no individual had a clinical diagnosis of jumper ’s knee . US demonstrated structural tendon changes in 11 tendons , but there was no neovascularisation on PD sonography . Conclusions : A clinical diagnosis of jumper ’s knee , together with structural tendon changes and neovascularisation visualised with sonography , was seen among Swedish elite junior volleyball players but not in matched not regularly sports active controls . Structural tendon change alone was seen in 10 % of the control tendons Background : Jumper ’s knee patellar tendinopathy is well known to be a common and difficult injury in volleyball . Knowledge about its aetiology and pathogenesis is sparse . Objective : To prospect ively follow clinical status , tendon structure and vascularity in elite junior volleyball players . Methods : 22 volleyball players ( 44 patellar tendons ) beginning their first grade at the Swedish National Centre for high school volleyball were continuously evaluated clinical ly and by ultrasonography ( US ) and power Doppler ( PD ) over the 3 school years . Results : At inclusion , there were 44 tendons being assessed . Jumper ’s knee was diagnosed clinical ly in eight patellar tendons ( seven of eight had structural changes and vascularity on US+PD ) . There were 27 normal ( clinical and US+PD ) tendons . At 3 years , there were 36 tendons still being assessed . Four individuals ( eight tendons ) had been excluded . Jumper ’s knee had developed in 2 of 25 ( 2 were excluded ) tendons that were normal ( clinical and US+PD ) at inclusion . Jumper ’s knee ( clinical and US+PD ) was also present in six tendons . Conclusions : Normal clinical tests and ultrasound findings at the start indicated a low risk for these elite junior volleyball players to sustain jumper ’s knee during three school years with intensive training and playing Training volume and body composition have been suggested as risk factors for jumper 's knee among athletic youth , but research is lacking . The aim of this 4-year prospect i ve cohort study was to examine the relationship between training and competition load , body composition , and risk for developing jumper 's knee . Participants are elite volleyball players , aged 16 - 18 years . Training and competition load was recorded continuously and body composition semiannually . Jumper 's knee was diagnosed on a st and ardized clinical examination . We recruited 141 healthy students ( 69 males and 72 females ) , and 28 developed jumper 's knee ( 22 boys and six girls ) . In a multivariate analyses , boys had three to four times higher risk compared with girls . Volleyball training had an odds ratio ( OR ) 1.72 ( 1.18 - 2.53 ) for every extra hour trained , and match exposure was the strongest sports-related predictor for developing jumper 's knee with an OR of 3.88 ( 1.80 - 8.40 ) for every extra set played per week . We did not detect any significant differences between the groups in body composition at the time of inclusion or in the change of body composition during the study period . Conclusion , male gender , a high volume of volleyball training and match exposure were risk factors for developing jumper 's knee 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 : Patellar tendinopathy ( PT ) is one of the most common reasons for sport-induced pain of the knee . Low ankle dorsiflexion range might predispose for PT because of load-bearing compensation in the patellar tendon . Purpose : The purpose of this 1-year prospect i ve study was to analyze if a low ankle dorsiflexion range increases the risk of developing PT for basketball players . Study Design : Cohort study ( prognosis ) ; Level of evidence , 2 . Methods : Ninety junior elite basketball players were examined for different characteristics and potential risk factors for PT , including ankle dorsiflexion range in the dominant and nondominant leg . Data were collected over a 1-year period and follow-up , including reexamination , was made at the end of the year . Results : Seventy-five players met the inclusion criteria . At the follow-up , 12 players ( 16.0 % ) had developed unilateral PT . These players were found to have had a significantly lower mean ankle dorsiflexion range at baseline than the healthy players , with a mean difference of −4.7 ° ( P = .038 ) for the dominant limb and −5.1 ° ( P = .024 ) for the nondominant limb . Complementary statistical analysis showed that players with dorsiflexion range less than 36.5 ° had a risk of 18.5 % to 29.4 % of developing PT within a year , as compared with 1.8 % to 2.1 % for players with dorsiflexion range greater than 36.5 ° . Limbs with a history of 2 or more ankle sprains had a slightly less mean ankle dorsiflexion range compared to those with 0 or 1 sprain ( mean difference , −1.5 ° to −2.5 ° ) , although this was only statistically significant for nondominant legs . Conclusion : This study clearly shows that low ankle dorsiflexion range is a risk factor for developing PT in basketball players . In the studied material , an ankle dorsiflexion range of 36.5 ° was found to be the most appropriate cutoff point for prognostic screening . This might be useful information in identifying at-risk individuals in basketball teams and enabling preventive actions . A history of ankle sprains might contribute to reduced ankle dorsiflexion range |
1,272 | 30,231,083 | Alveolar ridge preservation procedures are effective in minimizing post extraction hard tissue dimensional loss .
The outcomes of these procedures are affected by morphology of extraction sockets , type of wound closure , type of grafting material s , use of barrier membranes , and use of growth factors | PURPOSE Alveolar ridge preservation procedures have been advocated to minimize post extraction dimensional loss .
There is a need for systematic analyses of clinical factors affecting the outcomes of these procedures in order to improve their clinical outcomes .
This systematic review and meta- analysis aim ed to assess the efficacy of alveolar ridge preservation procedures in terms of hard tissue dimensional changes and to determine clinical factors affecting outcomes of these procedures . | OBJECTIVE To volumetrically evaluate soft tissue changes of different ridge preservation techniques compared to spontaneous healing 6 months after tooth extraction . MATERIAL S AND METHODS In each of 40 patients , one single-rooted tooth was extracted and four treatment modalities were r and omly assigned to the following groups ( n = 10 each ) : A ) ß-tricalcium-phosphate-particles with a polylactid coating ( ß-TCP ) , B ) demineralized bovine bone mineral with 10 % collagen covered with a collagen matrix ( DBBM-C/CM ) , C ) DBBM with 10 % collagen covered with an autogenous soft tissue punch graft ( DBBM-C/PG ) , D ) spontaneous healing ( control ) . Impressions were obtained before extraction and 6 months later , casts were digitized and volumetric changes at the buccal soft tissues were determined . One-way anova was performed and pair-wise Wilcoxon rank sum test with Bonferroni-Holm method was applied for comparison of differences between two groups . RESULTS After 6 months , horizontal contour changes accounted for -1.7 ± 0.7 mm ( A ) , -1.2 ± 0.5 mm ( B ) , -1.2 ± 0.7 mm ( C ) and -1.8 ± 0.8 mm ( D ) . None of the group comparisons reached statistical significance . CONCLUSIONS Six months after tooth extraction all groups revealed a horizontal volume change in the buccal soft tissue contour . Application of DBBM-C/CM or DBBM-C/PG reduced the amount of volume resorption compared to ß-TCP or spontaneous healing without reaching statistically significant difference Aim To evaluate the effects of autologous platelet rich fibrin gel ( PRF gel ) on bone regeneration following extraction . Material s and Methods The study design was approved by the Institutional Ethical Committee . Study sample consisting of a total of 22 patients requiring bilateral transalveolar third molar extraction s were included after written informed consent . One side was r and omly chosen as case and the other side was the control . Autologous PRF gel was prepared from Fresh blood obtained from the patient . The PRF gel was placed in the extraction site and primary closure was obtained . The patient was called for a follow up on the first post op day , 1st week , one month , three month and six months post op . Regeneration of bone was measured using serial radiographs ( RVG ) at immediate post op , one , three and six months . This was then compared with the bone regeneration seen in the control group , with the radiographs taken at same intervals , to estimate the difference in bone regeneration if any . RVGs were assessed for amount of radiologic bone filling by the method described by Matteo Chiapasco et al. Results and Conclusion Higher mean pixels was recorded in cases compared to controls at all the time intervals viz . , immediate post op , 1 month post op , 3 months post op and 6 months post op . However , the difference in the mean pixels recorded between the two groups was not statistically significant ( P > 0.05 ) . For complete analysis , further follow up of the present patients and a larger sample size is required to obtain a conclusive result of the Bone Regeneration in extraction sockets with PRF gel This radiographic study evaluated the efficacy of different concentrations of rhBMP-2 to regenerate bone in alveolar defects in the anterior maxilla . The study was performed using reasonably st and ardized CT examinations and the Simplant program . The radiographic measurements were further refined by careful st and ardization of the measured regions of interest . There was a statistically significant difference in bone formation between subjects treated with a concentration of 1.5 mg/mL rhBMP-2 compared with each of the other groups . There was no statistically significant difference in bone volume between any of the other groups . None of the groups showed a loss in bone volume AIM To investigate the influence of the use L-PRF as a socket filling material and its ridge preservation properties . MATERIAL S AND METHODS Twenty-two patients in need of single bilateral and closely symmetrical tooth extraction s in the maxilla or m and ible were included in a split-mouth RCT . Treatments were r and omly assigned ( L-PRF socket filling versus natural healing ) . CBCT scans were obtained after tooth extraction and three months . Scans were evaluated by superimposition using the original DICOM data . Mean ridge width differences between timepoints were measured at three levels below the crest on both the buccal and lingual sides ( crest -1 mm ( primary outcome variable ) , -3 mm and -5 mm ) . RESULTS Mean vertical height changes at the buccal were -1.5 mm ( ±1.3 ) for control sites and 0.5 mm ( ±2.3 ) for test sites ( p < 0.005 ) . At the buccal side , control sites values were , respectively , -2.1 ( ±2.5 ) , -0.3 mm ( ±0.3 ) ( p < 0.005 ) and -0.1 mm ( ±0.0 ) , and test sites values were , respectively , -0.6 mm ( ±2.2 ) ( p < 0.005 ) , -0.1 mm ( ±0.3 ) and 0.0 mm ( ±0.1 ) . Significant differences ( p < 0.005 ) were found for total width reduction between test ( -22.84 % ) and control sites ( -51.92 % ) at 1 mm below crest level . Significant differences were found for socket fill ( visible mineralized bone ) between test ( 94.7 % ) and control sites ( 63.3 % ) . CONCLUSION The use of L-PRF as a socket filling material to achieve preservation of horizontal and vertical ridge dimension at three months after tooth extraction is beneficial BACKGROUND Reduction of alveolar height and width after tooth extraction may present problems for implant placement , especially in the anterior maxilla where bone volume is important for biologic and esthetic reasons . Different graft material s have been proposed to minimize the reduction in ridge volume . The aim of this study was to compare radiographic and histomorphometric results of magnesium-enriched hydroxyapatite ( MHA ) and calcium sulfate ( CS ) grafts in fresh sockets after tooth extraction s. METHODS Forty-five fresh extraction sockets with three bone walls were selected in 15 patients . A split-mouth design was used : 15 sockets on the right side of the jaw received MHA , 15 sockets on the left side received CS , and 15 r and om unfilled sockets were considered the control ( C ) group . Intraoral digital radiographs were taken at baseline and at 3 months after graft material placement . At 3 months , cylinder bone sample s were obtained for histology and histomorphometry analysis . RESULTS The difference in mean radiographic vertical bone level from baseline to 3 months was -2.48 + /- 0.65 mm in the CS group , -0.48 + /- 0.21 mm in the MHA group , and -3.75 + /- 0.63 mm in the unfilled C group . Statistically significant differences ( P < 0.05 ) were found between CS and MHA groups and between MHA and C groups . Histologic examination revealed bone formation in all treated sites ; trabecular bone assessment did not differ among apical , mesial , and coronal portions of the specimens . Mean vital bone measurements for CS , MHA , and C groups were 45.0 % + /- 6.5 % , 40.0 % + /- 2.7 % , and 32.8 % + /- 5.8 % , respectively . Statistically significant differences ( P < 0.05 ) were found among all groups . Connective tissue percentages averaged 41.5 % + /- 6.7 % for the CS group , 41.3 % + /- 1.3 % for the MHA group , and 64.6 % + /- 6.8 % for the C group . Statistically significant differences ( P < 0.05 ) were found between CS and C groups and between MHA and C groups . The CS-grafted sockets showed 13.9 % + /- 3.4 % residual implant material , whereas the MHA-treated sockets showed 20.2 % + /- 3.2 % residual material . The difference between the groups was statistically significant ( P < 0.05 ) . CONCLUSIONS Radiographs revealed a greater reduction of alveolar ridge in the CS group than in the MHA group . Histologic examination showed more bone formation and faster resorption in the CS group and more residual implant material in the MHA group 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 BACKGROUND The placement of different graft material s and /or the use of occlusive membranes to cover the extraction socket entrance are techniques aim ed at preserving/reducing alveolar ridge resorption . The use of grafting material s in fresh extraction sockets has , however , been question ed because particles of the grafted material have been found in alveolar sockets 6 - 9 months following their insertion . AIM The aims of the study were to ( i ) . evaluate whether alveolar ridge resorption following tooth extraction could be prevented or reduced by the application of a bioabsorbable polylactide-polyglycolide sponge used as a space filler , compared to natural healing by clot formation , and ( ii ) . evaluate histologically the amount and quality of bone tissue formed in the sockets , 6 months after the use of the bioabsorbable material . MATERIAL AND METHODS Thirty-six patients , undergoing periodontal therapy , participated in this study . All patients were scheduled for extraction of one or more compromised teeth . Following elevation of full-thickness flaps and extraction of teeth , measurements were taken to evaluate the distance between three l and marks ( mesio-buccal , mid-buccal , disto-buccal ) on individually prefabricated stents , and the alveolar crest . Twenty-six alveolar sockets ( test ) were filled with a bioabsorbable polylactide-polyglycolide acid sponge ( Fisiograft ) , while 13 sockets ( controls ) were allowed to heal without any filling material . The flaps were sutured with no attempt to achieve primary closure of the surgical wound . Re-entry for implant surgery was performed 6 months following the extraction s. Thirteen biopsies ( 10 test and three control sites ) were harvested from the sites scheduled for implant placement . RESULTS The clinical measurements at 6 months revealed , in the mesial-buccal site , a loss of bone height of 0.2 mm ( 1.4 SD ) in the test and 0.6 mm ( 1.1 SD ) in the controls ; in the mid-buccal portion a gain of 1.3 mm ( 1.9 SD ) in the test and a loss of 0.8 mm ( 1.6 SD ) in the controls ; and in the distal portion a loss of 0.1 mm ( 1.1 SD ) in the test and of 0.8 ( 1.5 SD ) mm in the controls . The biopsies harvested from the test sites revealed that the new bone formed at 6 months was mineralized , mature and well structured . Particles of the grafted material could not be identified in any of the 10 test biopsies . The bone formed in the control sites was also mature and well structured . CONCLUSION The results of this study indicate that alveolar bone resorption following tooth extraction may be prevented or reduced by the use of a bioabsorbable synthetic sponge of polylactide-polyglycolide acid . The quality of bone formed seemed to be optimal for dental implant insertion INTRODUCTION The closure of post extraction gingival defects has not been studied in depth , although their achievement is of great importance in certain situations , such as prior to radiotherapy treatment in patients with oral cancer . The aim of this study is to assess the influence of bone substitutes on the time of closure of post extraction gingival defects . MATERIAL S AND METHODS 22 patients underwent two symmetrical dental extraction s. Using a split mouth model , with r and om assignment to one or other group , one was considered a control group ( no filling with any type of material post extraction ) , whereas the other was considered the experimental group ( filling with bone substitute and calcium sulphate post extraction ) . Gingival closure and healing were assessed in the first group at 2 , 3 , 4 and 6 weeks after extraction . RESULTS No differences were seen between both groups in gingival health . Gingival closure was greater and faster in the experimental group than in the control group , and was statistically significant in the first and second week after extraction ( 1st week , control : 19.63 mm(2 ) + /- 2.52 - -experimental : 11.76 mm(2 ) + /- 2.40 - p < 0.05 ) ( 2nd week , control : 15.09 mm(2 ) + /- 2.77 - -experimental : 7.98 mm(2 ) + /- 1.99 - p < 0.05 ) , although these differences evened out during subsequent periods . No medical accidents were seen and tolerance to treatment was good in both groups . DISCUSSION According to our data , the use of filling material allows a faster initial gingival closure of the socket post extraction . However , we must assess the cost of intervention , with the aim of applying it in situations in which it may be of significant advantage ( for example , patients that will undergo radiotherapy treatment ) , or in cases in which the use of these material s is justified due to other reasons in addition to the one mentioned ( such as maintenance of bone crest architecture for implant restoration ) The aim of this study was to compare the effectiveness of two bone substitute material s for socket preservation after tooth extraction . Extraction sockets in 10 patients were filled with either inorganic bovine bone material ( Bio-Oss ) or with synthetic material consisting of hydroxyapatite and silicon dioxide ( NanoBone ) . Extraction sockets without filling served as the control . The results demonstrate the effectiveness of the presented protocol for socket preservation and that the choice of a suitable bone substitute material is crucial . The dimensions of the alveolar ridge were significantly better preserved with Bio-Oss than with NanoBone or without treatment . Bio-Oss treatment result ed in better bone quality and quantity for successful implant placement OBJECTIVE The purpose of this prospect i ve single cohort study was to evaluate the use of xenograft and collagen membranes in treating full or partial buccal bone defects of fresh extraction sockets in the esthetic zone . MATERIAL S AND METHODS Thirty-three patients requiring tooth extraction in the anterior maxillary area and showing a complete or partial buccal bone plate deficiency ( more than 2 mm ) were consecutively enrolled and treated . Corticocancellous porcine bone and platelet-rich fibrin ( PRF ) with a collagen membrane were used to graft the extraction sockets , and the membranes were left exposed to the oral cavity with a secondary soft tissue healing . The outcome variables were as follows : width of keratinized mucosa , facial soft tissue levels , clinical bone changes ( measured with a clinical splint ) , implant and prosthesis failures , and peri-implant marginal bone changes . RESULTS All treated sites allowed the placement of implants ; the width of keratinized mucosa at the mid-facial aspect showed an increase of 2.3 mm 5 months after the grafting procedure , and its value was 3.2 ± 0.6 mm at 1-year follow-up . The mean values of the facial soft tissue level indicated an increase over time . The bone level showed an improvement of 0.8 ± 0.1 mm and 0.7 ± 0.1 mm at mesial and distal sites , respectively , when compared to the baseline measurements . Finally , in the palatal area , no bone changes were observed . No implant failed during the entire observation period . CONCLUSIONS Findings from this study showed that xenograft and PRF , used for ridge preservation of the extraction sockets with buccal bone plate dehiscence in the esthetic zone , can be considered effective in repairing bone defects before implant placement . The secondary soft tissue healing over the grafted sockets did not compromise bone formation ; moreover , the soft tissue level and the width of keratinized gingiva showed a significant improvement over time The purpose of this study was to evaluate the clinical effectiveness of a bioabsorbable membrane made of glycolide and lactide polymers in preserving alveolar ridges following tooth extraction using a surgical technique based on the principles of guided bone regeneration . Sixteen patients requiring extraction s of 2 anterior teeth or bicuspids participated in the study ( split-mouth design ) . Following elevation of buccal and lingual full-thickness flaps and extraction of teeth , experimental sites were covered with bioabsorbable membranes ; control sites did not receive any membrane . Titanium pins served as fixed reference points for measurements . Flaps were advanced in order to achieve primary closure of the surgical wound . No membrane became exposed in the course of healing . Reentry surgeries were performed at 6 months . Results showed that experimental sites presented with significantly less loss of alveolar bone height , more internal socket bone fill , and less horizontal resorption of the alveolar bone ridge . This study suggests that treatment of extraction sockets with membranes made of glycolide and lactide polymers is valuable in preserving alveolar bone in extraction sockets and preventing alveolar ridge defects TEN PATIENTS WHO REQUIRED two or more anterior teeth extraction s were utilized in this study . Extraction procedures were carried out with a full thickness surgical flap approach . After flap reflection , teeth were removed with a minimum of trauma to the surrounding bone . Following extraction silicone-based impression techniques were used to produce a model of the alveolar process and small metal pins were placed in the alveolus to be used as fixed points to make measurements of ridge dimensions . One socket was covered with an exp and ed polytetrafluoroethylene ( ePTFE ) barrier membrane ( experimental site ) ; the other socket was a conventional control . The soft tissue flaps were then mobilized using periosteal releasing incision and the wound closed with ePTFE mattress sutures . Six months following extraction , patients were treated with flap surgery to expose both extraction s sites to remove the ePTFE membranes and to measure ridge dimensions using the pins as fixed points . Clinical and model measurements have shown statistically significant better ridge dimensions at experimental sites than at control ( P < or = 0.05 ) . Three patients with exposed membranes had similar dimensional changes as controls . Results from this study suggested that this improved technique offers a predictable alveolar ridge maintenance enhancing the bone quality for dental implant procedures and esthetic restorative dentistry Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more OBJECTIVE To radiographically analyze extraction sites left untreated or treated using a socket preservation technique . MATERIAL S AND METHODS A total of 20 patients scheduled for single extraction in the maxilla from second to second premolar were enrolled in this study . All sites showed a bone defect > 5 mm at the buccal wall and no soft tissue recession . At baseline ( T0 ) , tooth extraction was performed ; subsequently , sites were r and omly allocated to the control ( CG : left to heal without grafting ) or test group ( TG : grafted using hydroxyapatite ) . Two months later ( T1 ) , implants were inserted and eventual GBR procedure was performed . Three months later , the definitive crown was placed . Follow up was 24 months ( T2 ) . A cone-beam computed tomographic examination ( CT ) was performed at each time point . At each radiographic analysis , horizontal and vertical widths of the sockets were measured . Comparisons between CG and TG were performed by a Wilcoxon non-parametric test . RESULTS At the end of the study , no patient dropped out and all implants inserted ( 10 in each group ) result ed integrated . GBR procedures were performed at T1 only in the CG . In the CG , the mean value of the horizontal width in the coronal CT slices was 0.98 mm ( ± 0.37 ) , 7.70 mm ( ± 0.92 ) , 7.45 mm ( ± 0.69 ) at T0 , T1 ( after bone regeneration ) and T2 , respectively . In the TG , the mean value of the horizontal width in the coronal CT slices was 0.96 mm ( ± 0.41 ) , 8.97 mm ( ± 1.91 ) , 9.48 mm ( ± 1.56 ) ; at T2 , it was 9.52 mm ( ± 1.87 ) at T0 ( pre- and post-socket preservation ) T1 and T2 , respectively . At each follow up , the mean horizontal bone width in TG was statistically significantly greater than in the control group ( P < 0.05 ) . At T0 , mean value of the vertical bone defect length ( BDL ) was 6.93 mm for TG , 6.5 mm for CG . At T1 and T2 , mean BDL value was 0 for both groups . Statistically significant difference was not found between TC and CG at any time point ( P > 0.05 ) . CONCLUSIONS This r and omized controlled trial suggested that in sites with buccal bone defects > 5 mm , the application of HA can minimize alveolar crest resorption following tooth extraction . Furthermore , compared with traditional regenerative procedure carried out following socket healing , this preservation technique seems to result in better horizontal regeneration of the buccal bone wall BACKGROUND Tooth extraction typically leads to loss of ridge width and height . The primary aim of this 6-month r and omized , controlled , blinded , clinical study was to determine whether ridge preservation would prevent post- extraction resorptive changes as assessed by clinical and histologic parameters . METHODS Twenty-four patients , 10 males and 14 females , aged 28 to 76 ( mean 51.5 + /- 13.6 ) , requiring a non-molar extraction and delayed implant placement were r and omly selected to receive either extraction alone ( EXT ) or ridge preservation ( RP ) using tetracycline hydrated freeze-dried bone allograft ( FDBA ) and a collagen membrane . A replaced flap , which did not completely cover the sockets , was used . Following extraction , horizontal and vertical ridge dimensions were determined using a modified digital caliper and an acrylic stent , respectively . Prior to implant placement , a 2.7 x 6.0 mm trephine core was obtained and preserved in formalin for histologic analysis . RESULTS The width of the RP group decreased from 9.2 + /- 1.2 mm to 8.0 + /- 1.4 mm ( P<0.05 ) , while the width of the EXT group decreased from 9.1 + /- 1.0 mm to 6.4 + /- 2.2 mm ( P<0.05 ) , a difference of 1.6 mm . Both the EXT and RP groups lost ridge width , although an improved result was obtained in the RP group . Most of the resorption occurred from the buccal ; maxillary sites lost more width than m and ibular sites . The vertical change for the RP group was a gain of 1.3 + /- 2.0 mm versus a loss of 0.9 + /- 1.6 mm for the EXT group ( P<0.05 ) , a height difference of 2.2 mm . Histologic analysis revealed more bone in the RP group : about 65 + /- 10 % versus 54 + /- 12 % in the EXT group . The RP group included both vital bone ( 28 % ) and non-vital ( 37 % ) FDBA fragments . CONCLUSIONS Ridge preservation using FDBA and a collagen membrane improved ridge height and width dimensions when compared to extraction alone . These dimensions may be more suitable for implant placement , especially in areas where loss of ridge height would compromise the esthetic result . The quantity of bone observed on histologic analysis was slightly greater in preservation sites , although these sites included both vital and non-vital bone . The most predictable maintenance of ridge width , height , and position was achieved when a ridge preservation procedure was employed After tooth extraction , varying amounts of bone resorption occur because of qualitative and quantitative changes at the edentulous site of the alveolar process . The aims of this r and omized controlled clinical trial were ( 1 ) to compare the post extraction changes in residual ridge dimensions during spontaneous healing with those during socket preservation , ( 2 ) to analyze the histologic and histomorphometric aspects of the grafted sockets , and ( 3 ) to compare probing procket depth ( PPD ) and clinical attachment level ( CAL ) changes at teeth adjacent to extraction sites . Forty-eight teeth were extracted from 41 patients referred for extraction of 1 or more maxillary or m and ibular premolars or molars . The edentulous sites were r and omly assigned to the control ( EXT , extraction alone ) or experimental groups ( SP , extraction and socket preservation ) . In the SP group , the sockets were filled with bovine bone mineral and covered with porcine collagen membrane . At baseline and after 4 months , PPD , gingival recession ( REC ) , and CAL were measured at teeth adjacent to the edentulous sites . The changes in ridge dimensions from baseline to 4 months were assessed on dental casts . At 4 months , bone was harvested from the grafted areas in the SP group and the edentulous areas in the EXT group . PPD , REC , and CAL were comparable between groups . However , from baseline to 4 months , the SP group showed significantly less reduction in ridge width ( 1.04 ± 1.08 mm vs 4.48 ± 0.65 mm , P < .001 ) and height ( 0.46 ± 0.46 mm vs 1.54 ± 0.33 mm , P < .001 ) . Histologically , the grafted sockets exhibited various stages of bone maturation and formation without inflammatory responses . No significant difference in the mineralized and nonmineralized fractions was noted between the groups . Socket preservation using bovine bone mineral and porcine collagen membrane considerably limits the amount of horizontal and vertical bone resorption when compared with extraction alone Aim The aim of this study was to investigate the influence of platelet-rich fibrin ( PRF ) on early wound healing and preservation of the alveolar ridge shape following tooth extraction . Methods In this clinical trial , 20 symmetrical , premolar extraction sockets using split-mouth design were r and omly selected with PRF or blood clot . The evaluations of wound healing , alveolar ridge contour changes , and crestal bone resorption were performed in dental casts and periapical radiographs ( T0 , initial ; T1 , 1 week ; T2 , 2 weeks ; T4 , 4 weeks ; T6 , 6 weeks ; T8 , 8 weeks ) . Results Platelet-rich fibrin clinical ly showed early healing of soft tissue covering socket orifices in the first 4 weeks . At the first week , the horizontal resorption on buccal aspect of PRF ( 1.07 ± 0.31 mm ) was significantly less than that of the control ( 1.81 ± 0.88 mm ) . Platelet-rich fibrin demonstrated the tendency to enter the steady stage after the fourth week following tooth extraction , whereas in the control group the progression of buccal contour contraction was still detected through the eighth week . Radiographically , the overall resorption of marginal bone levels at mesial and distal to the extraction site in PRF ( 0.70 , 1.23 mm ) was comparable to that of the control ( 1.33 , 1.14 mm ) . Although the PRF group demonstrated faster bone healing compared with the control , no statistically significant difference was detected . Conclusions This preliminary result demonstrated neither better alveolar ridge preservation nor enhanced bone formation of PRF in the extraction socket . The use of PRF revealed limited effectiveness by accelerated soft-tissue healing on the first 4 weeks INTRODUCTION As a consequence of extraction , the height of the buccal wall tends to decrease and results in the disappearance of bundle bone . To modify bone remodelling after extraction , various ridge preservation techniques have been proposed . The present research was drawn up with the following considerations in mind : to evaluate and to compare changes of hard and soft tissues in post- extraction sockets which received a ridge preservation procedure , with post- extraction sockets which had healed naturally . MATERIAL S AND METHODS Each patient was r and omly allocated to a test or control group using a specific software package . After extraction , the sockets were carefully inspected and any granulation tissue was removed . The control sites received silk sutures to stabilize the clot without any grafting material . The test sites were grafted with corticocancellous porcine bone and a collagen membrane . All experimental sites had the membranes left exposed to the oral cavity with a secondary wound healing . The thickness of the buccal alveolar bone , if present , was carefully measured at the time of tooth extraction using a calliper at 1 mm from the edge of the wall . The following clinical parameters were evaluated at baseline and after 4 months at implant placement : vertical bone changes , horizontal bone changes and width of keratinized gingiva . The length , diameter and need for additional bone augmentation were assessed for both groups at the time of implant insertion . RESULTS The control group showed vertical bone resorption of 1 ± 0.7 mm , 2.1 ± 0.6 mm , 1 ± 0.8 mm and 2 ± 0.73 mm at the mesial , vestibular , distal and lingual sites respectively . Moreover , changes in horizontal dimension showed an average resorption of 3.6 ± 0.72 mm . The test sites showed a horizontal bone remodelling of 0.3 ± 0.76 mm , 1.1 ± 0.96 mm , 0.3 ± 0.85 mm , 0.9 ± 0.98 mm at the mesial , vestibular , distal and lingual sites respectively . The horizontal bone resorption at the test sites was 1.6 ± 0.55 mm . The keratinized gingiva showed a coronal shift of 0.7 mm in the control group when compared to 1.1 mm in the test group . In addition , 42 % of sites in the control group required an additional bone augmentation at implant placement , when compared to 7 % in the test sites . CONCLUSIONS This study clearly points out that an alveolar ridge preservation technique performed with collagenated porcine bone and a resorbable membrane -- according to the procedure reported in this study --was able to limit the contour changes after tooth extraction . Finally , the test sites showed a better preservation of facial keratinized tissue when compared to control sites ; grafted sites allowed the placement of longer and wider implants when compared to implants inserted in non-grafted sites Objectives : The aims were to investigate whether the use of platelet-rich fibrin membranes ( PRF ) for socket filling could improve microarchitecture and intrinsic bone tissue quality of the alveolar bone after premolar extraction and to assess the influence of the surgical procedure before implant placement . Material and Methods : Twenty-three patients requiring premolar extraction followed by implant placement were r and omized to three groups : ( 1 ) simple extraction and socket filling with PRF , ( 2 ) extraction with mucosal flap and socket filling with PRF , and ( 3 ) controls with simple extraction without socket filling . Implant placement was performed at week 8 , and a bone biopsy was obtained for histomorphometric analysis . Results : Analysis by microcomputed tomography showed better bone healing with improvement of the microarchitecture ( P < 0.05 ) in group 1 . This treatment had also a significant effect ( P < 0.05 ) on intrinsic bone tissue quality and preservation of the alveolar width . An invasive surgical procedure with a mucosal flap appeared to completely neutralize the advantages of the PRF . Conclusions : These results support the use of a minimally traumatic procedure for tooth extraction and socket filling with PRF to achieve preservation of hard tissue BACKGROUND Bone grafting is a dynamic phenomenon . It is a surgical procedure that replaces missing bone with material either from patient 's own body , or , an artificial , synthetic or natural substitute . A successful bone graft when applied , heals , becomes incorporated , re-vascularises and eventually assumes the form desired . AIMS AND OBJECTIVE The main purpose of this present study was to radiologically assess and compare the regenerative potential of hydroxyapatite with Collagen ( G-Graft ) and hydroxyapatite ( G-Bone ) and to evaluate the clinical usefulness of these material s to enhance bone healing in third molar extraction sites through bone formation . MATERIAL S AND METHODS The study was carried out in the Department of Oral & Maxillofacilal Surgery , patients were divided into three groups . The rationale for assigning the patients to the groups was strictly r and om : Group I - G-Graft ( Hydroxyapatite with Collagen ) was used as Bone graft material , Group II - Bone graft material used was G-Bone ( Hydroxyapatite ) , Group III-control group ( no grafts was used ) . Orthopentomogram(OPG ) images were taken intra-operatively , just after extraction in the Group III ( control ) , after extraction but before graft placement in Group I & II ( study groups ) and post-operatively at the end of first month and third month . Bone density of the post- extraction sockets was measured at four r and om areas through ' densitometric analysis ' software in the OPG program ( Kodak 8000C Digital Panoramic System , Eastman Kodak Company ) and an average value was recorded at each review . RESULTS The percentage increase in bone density between 1(st ) month & 3(rd ) month was 7.55± 12.43 in Group I ( G Graft ) , 4.41± 5.4859 in Group II ( G Bone ) , while that Group III ( control ) was found to be -0.82 ± 3.96 . The bone density increase was found to be statistically highly significant ( p<0.01 ) ) between all groups . CONCLUSION The present study concluded that G-Graft has a definite regenerative potential and is better than G-bone and can be used in bony defects to enhance the bone healing without provoking any significant inflammatory process . The study also indicates that defects treated with G-Graft attain more density initially and that G-Graft enhances bone healing in early stage AIM To evaluate ( clinical ly , histologically , and histo-morphometrically ) the use of composite material s ( Biphasic calcium sulphate [ BCS ] with β Tri-Calcium Phosphate ( β-TCP ) and Hydroxyapatite [ HA ] ) in extraction socket sites and compare it to un-disturbed natural healing . MATERIAL AND METHODS Prospect i ve clinical trial of 36 patients ( 40 extraction sockets ) were r and omly assigned to either test or control group . Alveolar ridge horizontal dimension was measured in the middle of the socket at crest and 3 and 6 mm subcrestally . Crestal vertical height was measured at baseline surgery and at 4 month re-entry , at which time bone core biopsies were harvested from the center of the edentulous ridge . Histo-morphometric evaluation of the sample s was performed using hematoxylin & eosin stains and morphometric software . RESULTS The change in horizontal ridge width was higher in the control compared to the experimental group : 2.28 ± 2.36 mm versus 0.03 ± 2.32 mm ( p = .007 ) at -3 mm and 2.28 ± 2.43 versus 0.035 ± 3.05 ( p = .02 ) at -6 mm , for the experimental and control sites , respectively . The vertical distance form bone crest to neighboring horizontal line interconnecting the neighboring teeth was minimal in both groups ( 0.307 ± 2.01 mm versus 0.14 ± 2.03 mm [ p = 0.41 ] ) . Residual scaffolds occupied 15.99 ± 11.4 % of the volume in the grafted ( test ) sites while bone area fraction was not statistically different among the groups ( 47.7 ± 10.6 % versus 52.6 ± 11.6 % , test versus control , respectively p = .39 ) . The percentage of connective tissue in the control group was significantly higher that test group ( 36.3 ± 19.4 % versus 46.7 ± 10.6 % test versus control , respectively , p = .013 ) . CONCLUSION Ridge preservation technique using a combination of two synthetic bone grafts β-TCP and HA with BCS result ed in greater stability in the horizontal dimension after 4 months BACKGROUND The preservation of bone volume immediately after tooth removal might be necessary to optimize the success of implant placement in terms of esthetics and function . The objectives of this r and omized clinical trial were two-fold : 1 ) to compare the bone dimensional changes following tooth extraction with extraction plus ridge preservation using corticocancellous porcine bone and a collagen membrane ; and 2 ) to analyze and compare histologic and histomorphometric aspects of the extraction -alone sites to the grafted sites . METHODS Forty subjects who required tooth extraction and implant placement were enrolled in this study . Using a computer-generated r and omization list , the subjects were r and omly assigned to the control group ( EXT ; extraction alone ) or to the test group ( RP ; ridge-preservation procedure with corticocancellous porcine bone and collagen membrane ) . The following parameters were assessed immediately after extraction and 7 months prior to implant placement : plaque index , gingival index , bleeding on probing , horizontal ridge width , and vertical ridge changes . A bone biopsy was taken from the control and test sites 7 months after the surgical treatment . Histologic and histomorphometric analyses were also performed . RESULTS A significantly greater horizontal reabsorption was observed at EXT sites ( 4.3+/-0.8 mm ) compared to RP sites ( 2.5+/-1.2 mm ) . The ridge height reduction at the buccal side was 3.6+/-1.5 mm for the extraction -alone group , whereas it was 0.7+/-1.4 mm for the ridge-preservation group . Moreover , the vertical change at the lingual sites was 0.4 mm in the ridge-preservation group and 3 mm in the extraction -alone group . Forty biopsies were harvested from the experimental sites ( test and control sites ) . The biopsies harvested from the grafted sites revealed the presence of trabecular bone , which was highly mineralized and well structured . Particles of the grafted material could be identified in all sample s. The bone formed in the control sites was also well structured with a minor percentage of mineralized bone . The amount of connective tissue was significantly higher in the extraction -alone group than in the ridge-preservation group . CONCLUSIONS The ridge-preservation approach using porcine bone in combination with collagen membrane significantly limited the resorption of hard tissue ridge after tooth extraction compared to extraction alone . Furthermore , the histologic analysis showed a significantly higher percentage of trabecular bone and total mineralized tissue in ridge-preservation sites compared to extraction -alone sites 7 months after tooth removal OBJECTIVE To evaluate the radiographic changes of the alveolar ridge following application of different ridge preservation techniques 6 months after tooth extraction . MATERIAL S AND METHODS Four treatment modalities were r and omly assigned in 40 patients : β-tricalcium-phosphate-particles with polylactid coating ( β-TCP ) , demineralized bovine bone mineral with 10 % collagen covered with a collagen matrix ( DBBM-C/CM ) , DBBM-C covered with an autogenous soft-tissue graft ( DBBM-C/PG ) and spontaneous healing ( control ) . Cone-beam computed tomography scans were performed after treatment and 6 months later . RESULTS After 6 months , the vertical changes ranged between -0.6 mm ( -10.2 % ) for control and a gain of 0.3 mm ( 5.6 % ) for DBBM-C/PG on the lingual side , and between -2.0 mm ( -20.9 % ) for β-TCP and a gain of 1.2 mm ( 8.1 % ) for DBBM-C/PG on the buccal side . The most accentuated ridge width changes were recorded 1 mm below the crest : -3.3 mm ( -43.3 % , C ) , -6.1 mm ( -77.5 % , β-TCP ) , -1.2 mm ( -17.4 % , DBBM-C/CM ) and -1.4 mm ( -18.1 % , DBBM-C/PG ) . At all three levels , DBBM-C with either CM or PG was not significantly differing ( p > 0.05 ) , while most other differences between the groups reached statistical significance ( p < 0.05 ) . CONCLUSIONS Application of DBBM-C , covered with CM or PG , result ed in less vertical and horizontal changes of the alveolar ridge as compared with controls 6 months after extraction BACKGROUND Conventional dentoalveolar osseous reconstruction often involves the use of grafting material s with or without barrier membranes . The purpose of this study was to evaluate the efficacy of bone induction for the placement of dental implants by two concentrations of recombinant human bone morphogenetic protein-2 ( rhBMP-2 ) delivered on a bioabsorbable collagen sponge ( ACS ) compared to placebo ( ACS alone ) and no treatment in a human buccal wall defect model following tooth extraction . METHODS Eighty patients requiring local alveolar ridge augmentation for buccal wall defects ( > or = 50 % buccal bone loss of the extraction socket ) of the maxillary teeth ( bicuspids forward ) immediately following tooth extraction were enrolled . Two sequential cohorts of 40 patients each were r and omized in a double-masked manner to receive 0.75 mg/ml or 1.50 mg/ml rhBMP-2/ACS , placebo ( ACS alone ) , or no treatment in a 2:1:1 ratio . Efficacy was assessed by evaluating the amount of bone induction , the adequacy of the alveolar bone volume to support an endosseous dental implant , and the need for a secondary augmentation . RESULTS Assessment of the alveolar bone indicated that patients treated with 1.50 mg/ml rhBMP-2/ACS had significantly greater bone augmentation compared to controls ( P < or = 0.05 ) . The adequacy of bone for the placement of a dental implant was approximately twice as great in the rhBMP-2/ACS groups compared to no treatment or placebo . In addition , bone density and histology revealed no differences between newly induced and native bone . CONCLUSION The data from this r and omized , masked , placebo-controlled multicenter clinical study demonstrated that the novel combination of rhBMP-2 and a commonly utilized collagen sponge had a striking effect on de novo osseous formation for the placement of dental implants Following tooth removal bone formation normally takes 16 weeks and may result in less than adequate volume for the necessary reconstruction . Platelet rich plasma ( PRP ) has been promoted as an effective method for improving bone formation . Its use is often expensive , time consuming , or not clinical ly convenient for the patient and /or clinician . This study examines a simple method for obtaining a " Buffy Coat"-PRP ( BC-PRP ) and its effect on bone healing following the removal of bilateral m and ibular 3rd molars . Subtraction digital radiography and CT scan analysis were used to track changes in radiographic density at PRP treated sites in comparison to ipsilateral non-PRP treated sites . PRP treated sites demonstrated early and significant increased radiographic density over baseline measurements following tooth removal . The greatest benefit of PRP is during the initial 2-week postoperative healing time period ( P < .001 ) . During weeks 3 though 12 , BC-PRP treatment result ed in significant ( P < .0001 ) increases in bone density compared to control , but there was no significant interaction between time and treatment ( P > .05 ) . For the entire time period ( 0 - 25 weeks ) PRP treatment was significant ( P < .0001 ) and time was significant ( P < .0001 ) but there was no significant interaction ( P > .05 ) between the effect of PRP treatment and time . It required 6 weeks for control extraction sites to reach comparable bone density that PRP treated sites achieved at week 1 . Postoperative pain , bleeding , and numbness were not significantly affected by BC-PRP application . Results suggest that this simple technique may be of value to clinicians performing oral surgery by facilitating bone regeneration following tooth extraction BACKGROUND The aim of this r and omized , controlled clinical trial is to determine whether ridge preservation using an osteoinductive allograft ( test ) would prevent ridge resorption and promote bone maturation compared to extraction alone ( control ) . METHODS Seventeen patients ( 20 total sites ) , in need of a non-molar extraction and delayed implant placement were r and omly selected to receive either ridge preservation or extraction alone . A cone-beam computed tomography was completed with a radiographic stent in place before extraction and 10 to 12 weeks postoperatively for dimensional and buccal plate analyses . Bone cores were taken for micro-computed tomography ( microCT ) and histologic analyses . RESULTS Resorption of the alveolar ridge occurred at all sites with no statistically significant differences found between test and control sites . A significant correlation was found between the initial buccal plate thickness and the loss of vertical ridge height . microCT and histologic analyses found a mean new bone volume of 44.9 % with microCT and 37.4 % with histology in test sites and 39 % and 35.5 % , respectively , in control sites . The residual graft volume was 2.4 % with microCT and 4.5 % with histology . CONCLUSIONS Test and control sites lost similar amounts of alveolar ridge , with the loss of buccolingual width occurring predominantly at the expense of the buccal bone . A thicker buccal plate was associated with less ridge loss in the vertical dimension . The percentage of new bone was not statistically significant between either the test or control sites , using either microCT or histologic analyses Material and methods : Following tooth extraction , 30 patients were r and omly assigned to the following treatments ( Tx ) : Tx 1 : xenogenic bone substitute ( mp3 OsteoBiol , Tecnoss , Torino , Italy ) and free gingival graft ; Tx 2 : free gingival graft alone ; Tx 3 : xenogenic bone substitute ( mp3 OsteoBiol , Tecnoss , Torino , Italy ) , and Gore-Tex-Membran ( Gore-Tex CV5 , W.L. Gore & Associates , Putzbrunn , Germany ) ; Tx 4 : no further treatment ( control ) . Impressions were obtained before tooth extraction ( baseline ) and 4 months after surgery . Cast models were optically scanned , digitally superimposed and horizontal measurements of the contour alterations between time points taken via digital imaging analysis BACKGROUND An adequate alveolar crest is essential for implant placement in terms of esthetics and function . The objective of this r and omized clinical trial was to compare the preservation of the alveolar ridge dimensions following tooth extraction using porcine-derived xenograft combined with a membrane versus extraction -alone ( EXT ) sites . METHODS Fifteen patients who required double extraction of contralateral premolars and delayed implant placement were r and omly selected to receive both ridge-preservation procedure and EXT . The test sites ( alveolar ridge preservation [ ARP ] ) included 15 sockets treated using a corticocancellous porcine bone xenograft ( OsteoBiol ® Gen-Os ; Tecnoss srl , Giaveno , Italy ) associated with a soft cortical membrane ( OsteoBiol ® Lamina ; Tecnoss srl ) , while the corresponding control sites ( EXT ) were left without grafting for EXT . Horizontal and vertical ridge dimensions were recorded at baseline and 6 months after extraction s. RESULTS After 6 months , the EXT sites showed a significantly greater reabsorption of the buccolingual/palatal dimension of the alveolar ridge ( 3.7 ± 1.2 mm ) compared with the ARP sites ( 1.8 ± 1.3 mm ) . The mean vertical ridge height reduction in the control sockets was 3.1 ± 1.3 mm at the buccal sites and 2.4 ± 1.6 mm at the lingual sites compared with 0.6 ± 1.4 and 0.5 ± 1.3 mm , respectively , in the test sockets . The differences between test and control sockets were not significant for the mesial and distal measurements . CONCLUSIONS The placement of a porcine xenograft with a membrane in an extraction socket can be used to reduce the hard tissue reabsorption after tooth extraction compared with EXT BACKGROUND Preservation of the alveolar process after tooth extraction is desirable because it facilitates placement of endosseous implants and minimizes adverse esthetic results associated with fixed partial dentures . The purpose of this study was to evaluate the clinical effectiveness of bioactive glass used as a graft material combined with calcium sulfate used in the form of a mechanical barrier in preserving alveolar ridges after tooth extraction . METHODS Sixteen patients who required extraction of 2 anterior teeth or bicuspids participated in the study ( split mouth design ) . After tooth extraction and elevation of a buccal full-thickness flap , experimental sockets were filled with bioactive glass , which in turn was covered with a layer of calcium sulfate . Control sites did not receive any graft or calcium sulfate . Titanium pins served as fixed reference points for measurements . No attempt was made to advance the flap to cover the socket areas on control or experimental sites ( open socket approach ) . Reentry surgeries were performed at 6 months . RESULTS Reentry surgeries showed that experimental sites presented with ( 1 ) significantly more internal socket bone fill ( 6.43 + /- 2.78 mm vs 4.00 + /- 2.33 mm on control sites ) , ( 2 ) less ( although not statistically significantly less ) resorption of alveolar bone height ( 0.38 + /- 3.18 mm vs 1.00 + /- 2 . 25 mm on control sites ) , and ( 3 ) similar degree of horizontal resorption of the alveolar bony ridge as compared with controls ( 3 . 48 + /- 2.68 mm vs 3.06 + /- 2.41 mm on control sites ) . CONCLUSIONS This study suggests that treatment of extraction sockets with a combination of bioactive glass and calcium sulfate is of some benefit in preserving alveolar ridge dimensions after tooth extraction PURPOSE To investigate the effect of platelet-rich plasma ( PRP ) on the healing of hard and soft tissues of extraction sockets with a pilot study . MATERIAL AND METHODS Patients undergoing tooth extraction under intravenous sedation were asked to participate in the trial . Autologous platelet concentrates were prepared from the patients ' blood and autologous thrombin was produced . Outcome measures were : pain level , analgesic consumption , oral function ( ability to eat food , swallowing , mouth opening and speech ) , general activity , swelling , bruising , bleeding , bad taste or halitosis , food stagnation , patient satisfaction , healing complications , soft tissue healing , trabecular pattern of newly formed bone in extraction sockets , trabecular bone volume , trabecular separation , trabecular length , trabecular width , and trabecular number . Patients were followed up to 3 months post- extraction . RESULTS Twelve patients ( 15 sockets ) were r and omly allocated to the PRP group and 11 patients ( 14 sockets ) to the control group . Two patients from the control group did not attend any of the scheduled appointments following tooth extraction , and were considered dropouts . Additionally , one more patient from the control group and four patients from the PRP group did not attend their 3-month radiographic assessment appointments . Statistically significantly more pain was recorded in the control group for the first ( P=0.02 ) , second ( P=0.02 ) and third ( P=0.04 ) post-operative days for Visual Analogue Scale scores , whereas no differences were observed for the fourth ( P=0.17 ) , fifth ( P=0.38 ) , sixth ( P=0.75 ) and seventh ( P=0.75 ) post-operative days . There was a statistically significantly higher analgesic consumption for the first ( P=0.03 ) and second ( P=0.02 ) post-operative days in the control group and no differences thereafter . Differences in patients ' responses in the health-related quality of life question naire were statistically significant in favour of PRP treatment only for the presence of bad taste or bad smell in the mouth ( P=0.03 ) , and food stagnation in the operation area ( P=0.03 ) . The difference between groups was not statistically significant for patient satisfaction with the treatment ( P=0.31 ) . Regarding complications , two dry sockets and one acutely inflamed alveolus occurred in patients of the control group , which determined a borderline statistically significant difference in favour of the PRP group ( P=0.06 ) . Soft tissue healing was significantly better in patients treated with PRP ( P=0.03 ) . Radiographic evaluation carried out by the two blinded examiners revealed a statistically significant difference ( P=0.01 ) for sockets with dense homogeneous trabecular pattern , a borderline statistically significant difference in the trabecular pattern for bone volume ( P=0.06 ) favouring PRP use , and no significant differences for trabecular separation ( P=0.66 ) , trabecular length ( P=0.16 ) , trabecular width ( P=0.16 ) and trabecular number ( P=0.38 ) . CONCLUSIONS PRP may have some benefits in reducing complications such as alveolar osteitis and improving healing of soft tissue of extraction sockets . There were insufficient data to support the use of PRP to promote bone healing or to enhance the quality of life of patients following tooth extraction , although the sample size was too small to detect statistically significant differences The aim of this study was to evaluate and compare the dimensional changes in maxillary extraction sockets that have healed spontaneously and those treated with free gingival grafts . Ten subjects with at least two maxillary anterior teeth scheduled for extraction were selected for this study . Two maxillary teeth were allocated r and omly to either the test group or the control group . In the test group , the extraction socket was covered with a free gingival graft harvested from the palate , while in the control group the sockets healed spontaneously . Cone beam computed tomography ( CBCT ) scans were taken on the day of extraction and at 3 months postoperative . Soft tissue healing of the extraction sockets was assessed visually by clinical inspection . Hard tissue measurements were obtained from the CBCT scans . After 3 months of healing , the control sockets had lost height in the buccal and lingual crestal bones ( -1.03 and -0.56 mm , respectively ) ; however , the height in the buccal and lingual crestal bones was preserved at the test sites ( + 0.06 and + 0.25 mm , respectively ) . This difference between the two groups was statistically significant ( P<0.05 ) . In contrast , both the control and test groups lost width in the buccal and lingual crestal bones ; the difference between the control and test groups was not statistically significant ( P>0.05 ) . The authors propose that covering the orifice of the extraction socket with a free gingival graft can result in preservation of the alveolar bone height BACKGROUND The alveolar ridge undergoes reabsorption and atrophy subsequent to tooth removal and thus exhibits a wide range of dimensional changes . Preservation of the alveolar crest after tooth extraction is essential to enhance the surgical site before implant fixture placement . The aim of this r and omized clinical study is to investigate and compare the need for additional augmentation procedures at implant insertion , as well as the success rate and marginal bone loss for implants placed in the grafted sites versus those placed in naturally healed sites . METHODS Forty patients with ≥1 hopeless tooth were r and omly allocated to : 1 ) a test group , receiving extraction and grafting corticocancellous porcine bone ; and 2 ) a control group , receiving extraction without any graft . After 7 months of healing , implants were inserted in each of the sites . The implants were submerged and loaded after 4 months with metal-ceramic rehabilitation . The follow-up included evaluation of implant diameter and length , the need for additional augmentation procedures at implant placement , implant failure , and marginal bone level changes . All patients were followed over a 3-year period . RESULTS One implant failed in the control group at the second stage of surgery ( 6 months after placement ) ; one implant failed in the test group after 2 years of loading . The cumulative implant success rate at the 3-year follow-up visit reached 95 % for both groups . No statistically significant differences were detected for marginal bone changes between the two groups . CONCLUSIONS It was concluded that implants placed into grafted extraction sockets exhibited a clinical performance similar to implants placed into non-grafted sites in terms of implant survival and marginal bone loss . However , grafted sites allowed placement of larger implants and required less augmentation procedures at implant placement when compared to naturally healed sites Extraction of a tooth necessitated by factors such as developmental problems , trauma , severe periodontal disease and endodontic problems often causes deformities of the residual alveolar ridge in the maxillary anterior region . These cases are usually difficult to restore prosthetically and they result in poor esthetics and insufficient occlusal function . This study investigated the efficacy of root form bioactive glass cones implanted into ( a ) artificial sockets produced by bone splitting of previous extraction sites ( group BS ) and ( b ) fresh extraction sockets ( group FES ) . We included conventional extraction sockets sutured without implanting the root form bioactive glass cones as a control ( group C ) . A total of 16 patients were treated for whom extraction s had been indicated due to severe periodontitis . 6 patients with 7 implant sites having Class II or III alveolar ridge deformities comprised the BS group . 5 patients with 10 implant sites comprised the FES group . Group C , comprised 5 patients with 10 extraction sites . Alveolar ridge width and height measurements were obtained using study casts preoperatively , immediately postoperatively , and at 3 and 12 months after operation . In the BS group , while the width of the alveolar ridge increased by 2.8+/-1.18 mm immediately after ridge augmentation procedure and by 2.4+/-0.93 mm at 1 year after operation ( p<0.01 ) , the height of the alveolar ridge increased by 1.8+/-1.99 mm and 1.4+/-1.74 mm respectively ( p<0.05 ) . In the FES group , the differences between preoperative original ridge height and width and postoperative measurements were not statistically significant , which demonstrated the efficiency of this method in preserving the alveolar ridge . In group C , while alveolar ridge width after 12 months had not significantly changed , alveolar ridge height decreased significantly ( 1.35+/-1.05 mm , p<0.01 ) . After 12 months , no dehiscences were detected and the differences in height between the groups remained significant . The results of this study indicate that this procedure is efficient in reconstructing alveolar ridges deformed as a result of extraction , particularly relevant in relation to preparation for subsequent restorative treatment OBJECTIVES This pilot r and omised controlled clinical trial aim ed to evaluate the feasibility and effectiveness of using a polycaprolactone ( PCL ) scaffold in fresh extraction sockets for ridge preservation . The hypothesis was that the insertion of a 3D bioresorbable PCL scaffold in fresh extraction sockets allowed for normal bone healing and better maintenance of ridge dimensions after 6 months as compared to extraction sockets without the scaffold . MATERIAL AND METHODS Thirteen patients were r and omised to either the test group ( N = 6 ) where a PCL scaffold was inserted in the tooth socket after extraction or the control group ( N = 7 ) where no space filler was used . Alveolar ridge height and width measurements were made at baseline and 6 months post- extraction , for the evaluation of bone resorption . At 6 months , a core of bone was trephined out from the healed ridge for microcomputed tomographic ( micro CT ) and histological analyses , immediately before Stage I dental implant surgery . Stage II dental implant surgery was performed 4 - 6 months later . RESULTS There was less vertical ridge resorption in the test group compared to the control group , and the difference was statistically significant in the mesio-buccal aspect ( P = 0.008 ) . Micro CT and histological observations showed mainly mineralised bone formation in both groups , except for one specimen in the test group . CONCLUSIONS The insertion of a 3D bioresorbable PCL scaffold in fresh extraction sockets allowed for normal bone healing , and there was better maintenance of ridge height after 6 months as compared to extraction sockets without the scaffold Alendronate is a bisphosphonate frequently used to reduce bone resorption . It has been used for osteoporosis , Paget 's disease , and also as adjunctive therapy for periodontal disease . The aim of this study was to evaluate the effect of systemic alendronate with or without endoalveolar collagen sponge on vertical bone resorption after lower wisdom tooth extraction . Forty patients referred for wisdom tooth impaction were selected . Before surgery , patients were r and omly assigned to receive one of the following pharmacologic treatments : no medication ( group 1 ) , postextractive endoalveolar collagen sponge ( group 2 ) , systemic alendronate for 4 months starting the day of surgery ( group 3 ) , and group 2 + group 3 ( group 4 ) . St and ardized orthopantomographic evaluation was obtained during recruitment ( T1 ) , immediately after surgery ( T2 ) , and 4 months ( T3 ) to evaluate crestal and alveolar socket changes . Results indicate that at T2 , crest and socket level did not show significant differences between the four groups . At T3 , test sites treated showed less bone resorption compared with controls . In particular , higher vertical bone height levels and a faster intraalveolar healing were achieved in groups 3 and 4 . Systemically given alendronate may be used successfully to reduce vertical bone resorption after wisdom tooth extraction PURPOSE The aim of this study was to evaluate the potential of an autologous bone marrow graft in preserving the alveolar ridges following tooth extraction . MATERIAL S Thirteen patients requiring extraction s of 30 upper anterior teeth were enrolled in this study . They were r and omized into two groups : seven patients with 15 teeth to be extracted in the test group and six patients with 15 teeth to be extracted in the control group . Hematologists collected 5 ml of bone marrow from the iliac crest of the patients in the test group immediately before the extraction s. Following tooth extraction and elevation of a buccal full-thickness flap , titanium screws were positioned throughout the buccal to the lingual plate and were used as reference points for measurement purpose s. The sockets were grafted with an autologous bone marrow in the test sites and nothing was grafted in the control sites . After 6 months , the sites were re-opened and bone loss measurements for thickness and height were taken . Additionally , before implant placement , bone cores were harvested and prepared for histologic and histomorphometric evaluation . RESULTS The test group showed better results ( P<0.05 ) in preserving alveolar ridges for thickness , with 1.14+/-0.87 mm ( median 1 ) of bone loss , compared with the control group , which had 2.46+/-0.4 mm ( median 2.5 ) of bone loss . The height of bone loss on the buccal plate was also greater in the control group than in the test group ( P<0.05 ) , 1.17+/-0.26 mm ( median 1 ) and 0.62 + 0.51 ( median 0.5 ) , respectively . In five locations in the control group , expansion or bone grafting complementary procedures were required to install implants while these procedures were not required for any of the locations in the test group . The histomorphometric analysis showed similar amounts of mineralized bone in both the control and the test groups , 42.87+/-11.33 % ( median 43.75 % ) and 45.47+/-7.21 % ( median 45 % ) , respectively . CONCLUSION These findings suggest that the autologous bone marrow graft can contribute to alveolar bone repair after tooth extraction Objective : The purpose of this study was to evaluate the efficacy of the alveolar ridge preservation technique using collagen sponge and xenograft after extraction . Study Design : Twenty patients were divided into the control group and the experimental group , which contained about 10 patients each . The control group patients were planned 3-unit bridge without performing implant and without special treatments for the extraction socket , and prosthetic treatments were performed after 3 months . In the experimental group , using collagen sponge and xenogeneic bone graft , alveolar ridge preservation was performed simultaneously with tooth extraction ; implants were placed after 3 months . Clinical and histological evaluations and statistical analysis were performed . Results : The resorption rate of the width of alveolar bone 3 mm below the alveolar ridge of the control group was shown to be 20.74 % and of the experimental group was an average of 14.26 % , approximately a difference of 6 % was observed , and it was statistically significant . New bone formation in the vicinity of bone graft material s was achieved well , and inflammation findings were not observed . Conclusion : The results indicated that in the ridge preservation using collagen sponge and xenograft , xenograft prevents the horizontal resorption of the alveolar ridge , and the upper collagen sponge blocks the infiltration of soft tissues to the lower area , and thus it has the advantage of the enhancement of bone fill The aim of this pilot study was to obtain preliminary data regarding the effectiveness of three different alveolar ridge preservation modalities as compared with a control . Subjects in need of single-rooted tooth extraction were recruited and r and omly allocated to one of four treatment groups : group 1 (control)--collagen plug ; group 2 - -socket grafting and polytetrafluoroethylene ( PTFE ) barrier ; group 3 - -socket grafting , buccal overbuilding , and PTFE barrier ; group 4 - -socket grafting , collagen barrier , and PTFE barrier . The grafting material used in all groups was an allograft . At 16 weeks , surgical reentry was performed , and a bone core biopsy was harvested for histomorphometric analysis . A cone beam computed tomography scan was obtained at baseline and before surgical reentry . Clinical ( keratinized mucosa [ KM ] and buccolingual ridge width [ RW ] changes ) and volumetric outcomes were statistically analyzed . A total of 20 patients were recruited ( 5 patients per group ) . KM and buccolingual RW changes were minimal during the 16-week healing period for all groups , with no statistically significant differences . Volumetric analyses revealed comparable alveolar ridge resorption values for groups 1 , 2 , and 4 ( 3 % , 7 % , and 5 % , respectively ) , while group 3 exhibited more reduction ( 16 % ) . Histomorphometric analysis revealed the presence of adequate average values of mineralized tissue ( group 1 , 46.4 % ; group 2 , 28.88 % ; group 3 , 48.81 % ; group 4 , 41.13 % ) . Based on the clinical and volumetric outcomes , none of the ridge preservation modalities was superior to the control . The combination allograft ( freeze-dried bone allograft and demineralized freeze-dried bone allograft ) employed in this study appears to be a safe and adequate bio material for intraoral grafting |
1,273 | 30,402,255 | Conclusion Among patients resuscitated from OHCA , early coronary angiography is associated with increased survival to discharge and favourable neurological outcome | Background Although acute myocardial infa rct ion is a common cause of out-of-hospital cardiac arrest ( OHCA ) , the role of early coronary angiography in OHCA remains uncertain .
We conducted a meta- analysis of observational studies to determine the association of early coronary angiography with survival in OHCA . | Background — Despite intensive efforts over many years , the United States has made limited progress in improving rates of survival from out-of-hospital cardiac arrest . Recently , national organizations , such as the American Heart Association , have focused on promoting byst and er cardiopulmonary resuscitation , use of automated external defibrillators , and other performance improvement efforts . Methods and Results — Using the Cardiac Arrest Registry to Enhance Survival ( CARES ) , a prospect i ve clinical registry , we identified 70 027 U.S. patients who experienced an out-of-hospital cardiac arrest between October 2005 and December 2012 . Using multilevel Poisson regression , we examined temporal trends in risk-adjusted survival . After adjusting for patient and cardiac arrest characteristics , risk-adjusted rates of out-of-hospital cardiac arrest survival increased from 5.7 % in the reference period of 2005 to 2006 to 7.2 % in 2008 ( adjusted risk ratio , 1.27 ; 95 % confidence interval , 1.12–1.43 ; P<0.001 ) . Survival improved more modestly to 8.3 % in 2012 ( adjusted risk ratio , 1.47 ; 95 % confidence interval , 1.26–1.70 ; P<0.001 ) . This improvement in survival occurred in both shockable and nonshockable arrest rhythms ( P for interaction=0.22 ) and was also accompanied by better neurological outcomes among survivors ( P for trend=0.01 ) . Improved survival was attributable to both higher rates of prehospital survival , where risk-adjusted rates increased from 14.3 % in 2005 to 2006 to 20.8 % in 2012 ( P for trend<0.001 ) , and in-hospital survival ( P for trend=0.015 ) . Rates of byst and er cardiopulmonary resuscitation and automated external defibrillator use modestly increased during the study period and partly accounted for prehospital survival trends . Conclusions — Data drawn from a large subset of U.S communities suggest that rates of survival from out-of-hospital cardiac arrest have improved among sites participating in a performance improvement registry BACKGROUND Timing of coronary angiography ( CAG ) is still controversial in the out-of-hospital cardiac arrest survivors who present without ST-segment elevation . METHODS AND RESULTS We analysed a prospect i ve registry of 158 comatose survivors of out-of-hospital cardiac arrest . For further analysis , we included 99 patients without ST-segment elevation on the initial electrocardiogram . All patients underwent temperature management . Urgent CAG ( < 2h from admission ) was performed in 25 % of the patients . A definite cause of the cardiac arrest could be identified during the index hospitalization in 82 patients : 36 had a non-ST-segment elevation acute coronary syndrome ( NSTE-ACS ) and 46 had a non-ACS diagnosis . Eighty-seven patients ( 88 % ) survived the index hospitalization and 65 ( 66 % ) were alive at six months . A favourable neurological status ( cerebral performance category ≤ 2 ) was observed in 56 % of the patients at discharge and in 56 % after six months of follow-up . Neither the survival nor the neurological outcome differed between the patients in whom the CAG was performed urgently upon the admission and the patients in whom the CAG was initially not performed , regardless of the aetiology of the cardiac arrest . On the other h and , performing an urgent CAG was safe and it did not prolong the average time to achieve an effective hypothermia . CONCLUSIONS Performing an urgent CAG in comatose cardiac arrest survivors without ST-segment elevation was not associated with better clinical and neurological outcome as compared to the initially conservative approach Purpose To investigate whether early coronary angiography ( CAG ) after out-of-hospital cardiac arrest of a presumed cardiac cause is associated with improved outcomes in patients without acute ST elevation . Methods The target temperature management after out-of-hospital cardiac arrest ( TTM ) trial showed no difference in all-cause mortality or neurological outcome between an intervention of 33 and 36 ° C . In this post hoc analysis , 544 patients where the admission electrocardiogram did not show acute ST elevation were included . Early CAG was defined as being performed on admission or within the first 6 h after arrest . Primary outcome was mortality at the end of trial . A Cox proportional hazard model was created to estimate hazard of death , adjusting for covariates . In addition , a propensity score matched analysis was performed . Results A total of 252 patients ( 46 % ) received early CAG , whereas 292 ( 54 % ) did not . At the end of the trial , 122 of 252 patients who received an early CAG ( 48 % ) and 159 of 292 patients who did not ( 54 % ) had died . The adjusted hazard ratio for death was 1.03 in the group that received an early CAG ; 95 % CI 0.80–1.32 , p = 0.82 . In the propensity score analysis early CAG was not significantly associated with survival . Conclusions In this post hoc observational study of a large r and omized trial , early coronary angiography for patients without acute ST elevation after out-of-hospital cardiac arrest of a presumed cardiac cause was not associated with improved survival . A r and omized trial is warranted to guide clinical practice AIM OF THE STUDY To question the beneficial effects of the recommended early percutaneous coronary intervention ( PCI ) after out-of-hospital cardiac arrest on 30-day survival with favourable neurological outcome . METHODS Prospect ively collected data of 1277 out of hospital cardiac arrest patients between 2005 and 2010 from a registry at a tertiary care university hospital were used for a cohort study . RESULTS In 494 ( 39 % ) arrest patients ST-segment elevation was identified in 249 ( 19 % ) . Within 12h after restoration of spontaneous circulation catheter laboratory investigations were initiated in 197 ( 79 % ) and PCI in 183 ( 93 % ) ( 78 % got PCI in less than 180 min ) . Adjustment for a cumulative time without chest compressions < 2 min , initial shockable rhythm , cardiac arrest witnessed by healthcare professionals , and a higher core temperature at time of hospitalization reduced the effect of PCI on favourable neurological outcome at 30 days ( OR 1.40 ; 95 % CI , 0.53 - 3.7 ) compared to the univariate analysis ( OR 2.52 ; 95 % CI , 1.42 - 4.48 ) . CONCLUSION This cohort study failed to demonstrate the beneficial effects of PCI as part of post-resuscitation care on 30-day survival with a favourable neurological outcome Background : Aggressive post-resuscitation care , in particular combining mild therapeutic hypothermia ( MTH ) with early coronary angiography ( CAG ) and percutaneous coronary intervention ( PCI ) , may improve prognosis after out-of-hospital cardiac arrest ( OHCA ) . Objectives : The study aims to assess the value of immediate CAG or PCI in comatose survivors after OHCA treated with MTH and their association with outcomes . Methods : Observational , prospect i ve analysis of all comatose , resuscitated patients treated with MTH at a tertiary centre and undergoing CAG or PCI ≤6 hours after OHCA , or non-invasively managed . Primary outcomes were 30-day and 1-year survival . Results : From March 2004–December 2012 , 141 ( 51 % ) out of 278 comatose patients after cardiac OHCA were treated with MTH ( median age : 64.5 ( interquartile range 55–73 ) years , males : 67 % , first shockable rhythm : 70 % , witnessed OHCA : 94 % , interval OHCA-resuscitation≤20 min : 81 % ) . Ninety-seven patients ( 69 % ) underwent early CAG , and 45 ( 32 % ) of them PCI . Patients undergoing CAG or PCI had a more favourable risk profile than subjects non-invasively managed . PCI treated patients had more bleedings , but no stent thrombosis occurred . Thirty-day and one-year unadjusted total mortality rates were 50 % and 72 % for non-invasively managed patients , 26 % and 38.7 % for patients su bmi tted only to CAG and 32 % and 36.6 % for patients treated with PCI ( p=0.0435 for early death , and p<0.0001 for one-year mortality , respectively ) . However , a propensity-matched score analysis did not confirm the survival advantage of invasive management ( p=0.093 ) . At multivariable analysis , clinical and OHCA-related variables as well as CAG , but not PCI , were associated with outcomes . Conclusions : Comatose patients cooled after OHCA and su bmi tted to emergency CAG or PCI are a favourable outcome population that receives optimal post-arrest care AIM OF STUDY Favourable hospital survival increased from 26 % to 56 % in the implementation phase of a new st and ard operating procedure ( SOP ) for treatment after out-of hospital cardiac arrest ( OHCA ) in 2003 . We now evaluate protocol adherence and survival rates after five years with this established SOP . METHODS This observational study is based on prospect ively collected registry data from all OHCA patients with cardiac aetiology admitted with spontaneous circulation to Ulleval Hospital between September 2003 and January 2009 . Three patient categories are described based on early assessment in the emergency department : conscious , comatose , and comatose patients receiving only palliative care , with main focus on comatose patients receiving active treatment . RESULTS Of 248 patients , 22 % were consciousness on admission , 70 % were comatose and received active treatment , while 8 % received only palliative care . Favourable survival from admittance to discharge remained at 56 % throughout the study period . Among actively treated patients 83 % received emergency coronary angiography and 48 % underwent subsequent percutaneous coronary intervention . In this cohort 63 % had an acute myocardial infa rct ion , ten of whom did not receive emergency coronary angiography . Among actively treated comatose patients , 6 % survived with unfavourable neurology , while 51 % of the deaths followed treatment withdrawal after prognostication of severe brain injury . CONCLUSION The previously reported doubling in survival rate remained throughout a five-year study period . Establishing reliable indication for emergency coronary angiography and interventions and validating prognostication rules in the hypothermia era are important challenges for future studies AIM To determine if early cardiac catheterization ( CC ) is associated with improved survival in comatose patients who are resuscitated after cardiac arrest when electrocardiographic evidence of ST-elevation myocardial infa rct ion ( STEMI ) is absent . METHODS We conducted a retrospective observational study of a prospect i ve cohort of 754 consecutive comatose patients treated with therapeutic hypothermia ( TH ) following cardiac arrest . RESULTS A total of 269 ( 35.7 % ) patients had cardiac arrest due to a ventricular arrhythmia without STEMI and were treated with TH . Of these , 122 ( 45.4 % ) received CC while comatose ( early CC ) . Acute coronary occlusion was discovered in 26.6 % of patients treated with early CC compared to 29.3 % of patients treated with late CC ( p=0.381 ) . Patients treated with early CC were more likely to survive to hospital discharge compared to those not treated with CC ( 65.6 % vs. 48.6 % ; p=0.017 ) . In a multivariate regression model that included study site , age , byst and er CPR , shock on admission , comorbid medical conditions , witnessed arrest , and time to return of spontaneous circulation , early CC was independently associated with a significant reduction in the risk of death ( OR 0.35 , 95 % CI 0.18 - 0.70 , p=0.003 ) . CONCLUSIONS In comatose survivors of cardiac arrest without STEMI who are treated with TH , early CC is associated with significantly decreased mortality . The incidence of acute coronary occlusion is high , even when STEMI is not present on the postresuscitation electrocardiogram Background —Whether to perform or not an immediate percutaneous coronary intervention ( PCI ) after out-of-hospital cardiac arrest is still debated . We aim ed to evaluate the impact of PCI on short- and long-term survival in out-of-hospital cardiac arrest patients admitted after successful resuscitation . Methods and Results —Between 2000 and 2013 , all nontrauma out-of-hospital cardiac arrest patients admitted in a Parisian cardiac arrest center after return of spontaneous circulation were prospect ively included . The association between immediate PCI and short- and long-term mortality was analyzed using logistic regression and Cox multivariate analysis , respectively . Propensity score-matching method was used to assess the influence of PCI on short- and long-term survival . During the study period , 1722 patients ( 71.5 % male , median age 60 [ 49.6 , 72.2 ] years ) were analyzed : 628 ( 35.6 % ) without coronary angiography , 615 ( 35.7 % ) with coronary angiography without PCI , and 479 ( 27.8 % ) with both . Among these groups , day 30 and year-10 survival rates were 21 % and 11.9 % , 35 % and 29 % , 43 % and 38 % , respectively ( P<0.01 for each ) . PCI as compared with no coronary angiography was associated with a lower day-30 and long-term mortality ( adjORcoro with PCI versus no coro 0.71 , 95 % confidence interval [ 0.54 , 0.92 ] ; P=0.02 and adjHRcoro with PCI versus no coro 0.44 , 95 % confidence interval [ 0.27 , 0.71 ] ; P<0.01 , respectively ) . PCI remained associated with a lower risk of long-term mortality ( adjHR 0.29 ; 95 % confidence interval [ 0.14 , 0.61 ] ; P<0.01 ) in propensity score-matching analysis . Conclusions —Immediate PCI after out-of-hospital cardiac arrest was associated with significant reduced risk of short- and long-term mortality . These findings should suggest physicians to consider immediate coronary angiography and PCI if indicated in these patients |
1,274 | 29,190,418 | We found little convincing evidence for a clinical ly-important effect on participants ' weight or BMI of any of the evaluated interventions .
As only two studies reported on cost , we know little about cost effectiveness across the evaluated interventions | BACKGROUND The prevalence of overweight and obesity is increasing globally , an increase which has major implication s for both population health and costs to health services .
This is an up date of a Cochrane Review .
OBJECTIVES To assess the effects of strategies to change the behaviour of health professionals or the organisation of care compared to st and ard care , to promote weight reduction in children and adults with overweight or obesity . | 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 OBJECTIVE Compare weight loss and maintenance between a face-to-face ( FTF ) weight management clinic and a clinic delivered via virtual reality ( VR ) . METHODS Participants were r and omized to 3 months of weight loss with a weekly clinic delivered via FTF or VR and then 6 months ' weight maintenance delivered with VR . Data were collected at baseline and 3 and 6 months for weight and process variables . Twenty overweight and obese individuals ( 31.1 ± 3.6 years of age ; body mass index , 32.8 ± 5.1 ; 85 % females ; 20 % minorities ) responded to advertisement and met inclusion criteria . Diets ( 1,200 - 1,800 kcal/d ) used prepackaged meals , fruits and vegetables , and physical activity ( 300 min/wk ) . RESULTS Weight loss was significantly greater for FTF at 10.8 % compared with 7.6 % for VR ( P < .05 ) . However , weight maintenance was significantly greater for VR at 14.0 % compared with 9.5 % for FTF ( P < .05 ) . CONCLUSIONS AND IMPLICATION S Virtual reality compares favorably with FTF for weight loss and may facilitate greater weight maintenance OBJECTIVE To compare two strategies for childhood obesity management : ambulatory assistance ( individual ) and educational program ( in group ) . METHOD Children and adolescents from 7 to 13 years of age were selected at r and om . They were divided into two groups : individually assisted or assisted in groups . An educational program about childhood obesity was created , with monthly meetings that consisted of lectures with parents ' participation and group work . Simultaneously , children and teenagers of the other group received individual ambulatory assistance . The program took place for six months . Body composition , eating habits and physical activities were assessed before and after interventions . RESULTS The sample comprised 38 children and adolescents whose mean age was 9.9 years . The program was more effective in increasing physical activity ( p = 0.003 ) , specially walking ( p = 0.003 ) , as well as in reducing total cholesterol ( p = 0.038 ) . Reduction of body mass index , obesity index and caloric intake was similar in both groups . As for food habits , ambulatory assistance increased the intake of fruits ( p = 0.033 ) and vegetables ( p = 0.002 ) and reduced the amount of French fries and crisps ( p = 0.041 ) , while children participating in the program reduced the intake of soft drinks ( p = 0.022 ) , s and wiches , pizza and fast food ( p = 0.006 ) . CONCLUSIONS Both strategies for h and ling childhood obesity were favorable to changes in food and physical activity habits . Group assistance was as effective as individual assistance , consolidating it as an alternative for obesity treatment Objectives To test the impact of provider performance pay for anaemia reduction in rural China . Design A cluster r and omised trial of information , subsidies , and incentives for school principals to reduce anaemia among their students . Enumerators and study participants were not informed of study arm assignment . Setting 72 r and omly selected rural primary schools across northwest China . Participants 3553 fourth and fifth grade students aged 9 - 11 years . All fourth and fifth grade students in sample schools participated in the study . Interventions Sample schools were r and omly assigned to a control group , with no intervention , or one of three treatment arms : ( a ) an information arm , in which principals received information about anaemia ; ( b ) a subsidy arm , in which principals received information and unconditional subsidies ; and ( c ) an incentive arm , in which principals received information , subsidies , and financial incentives for reducing anaemia among students . Twenty seven schools were assigned to the control arm ( 1816 students at baseline , 1623 at end point ) , 15 were assigned to the information arm ( 659 students at baseline , 596 at end point ) , 15 to the subsidy arm ( 726 students at baseline , 667 at end point ) , and 15 to the incentive arm ( 743 students at baseline , 667 at end point ) . Main outcome measures Student haemoglobin concentrations . Results Mean student haemoglobin concentration rose by 1.5 g/L ( 95 % CI –1.1 to 4.1 ) in information schools , 0.8 g/L ( –1.8 to 3.3 ) in subsidy schools , and 2.4 g/L ( 0 to 4.9 ) in incentive schools compared with the control group . This increase in haemoglobin corresponded to a reduction in prevalence of anaemia ( Hb < 115 g/L ) of 24 % in incentive schools . Interactions with pre-existing incentives for principals to achieve good academic performance led to substantially larger gains in the information and incentive arms : when combined with incentives for good academic performance , associated effects on student haemoglobin concentration were 9.8 g/L ( 4.1 to 15.5 ) larger in information schools and 8.6 g/L ( 2.1 to 15.1 ) larger in incentive schools . Conclusions Financial incentives for health improvement were modestly effective . Underst and ing interactions with other motives and pre-existing incentives is critical . Trial registration number IS RCT N76158086 Background : Primary care providers often fail to identify patients who are overweight or obese or discuss weight management with them . Electronic health record-based tools may help providers with the assessment and management of overweight and obesity . Purpose : We describe the design of a trial to examine the effectiveness of electronic health record-based tools for the assessment and management of overweight and obesity among adult primary care patients , as well as the challenges we encountered . Methods : We developed several new features within the electronic health record used by primary care practice s affiliated with Brigham and Women ’s Hospital in Boston , MA . These features included ( 1 ) reminders to measure height and weight , ( 2 ) an alert asking providers to add overweight or obesity to the problem list , ( 3 ) reminders with tailored management recommendations , and ( 4 ) a Weight Management screen . We then conducted a pragmatic , cluster-r and omized controlled trial in 12 primary care practice s. Results : We r and omized 23 clinical teams ( “ clinics ” ) within the practice s to the intervention group ( n = 11 ) or the control group ( n = 12 ) . The new features were activated only for clinics in the intervention group . The intervention was implemented in two phases : the height and weight reminders went live on 15 December 2011 ( Phase 1 ) , and all of the other features went live on 11 June 2012 ( Phase 2 ) . Study enrollment went from December 2011 through December 2012 , and follow-up ended in December 2013 . The primary outcomes were 6-month and 12-month weight change among adult patients with body mass index ≥25 who had a visit at one of the primary care clinics during Phase 2 . Secondary outcome measures included the proportion of patients with a recorded body mass index in the electronic health record , the proportion of patients with body mass index ≥25 who had a diagnosis of overweight or obesity on the electronic health record problem list , and the proportion of patients with body mass index ≥25 who had a follow-up appointment about their weight or were prescribed weight loss medication . Lessons learned : We encountered challenges in our development of an intervention within the existing structure of an electronic health record . For example , although we decided to r and omize clinics within primary care practice s , this decision may have introduced contamination and led to some imbalance of patient characteristics between the intervention and control practice s. Using the electronic health record as the primary data source reduced the cost of the study , but not all desired data were recorded for every participant . Conclusion : Despite the challenges , this study should provide valuable information about the effectiveness of electronic health record-based tools for addressing overweight and obesity in primary care Abstract Objective To evaluate a training programme intended to improve the management of obesity , delivered to general practice teams . Design Cluster r and omised trial . Setting Northern and Yorkshire region of Engl and Participants 44 general practice s invited consecutively attending obese adults to participate ; 843 patients attended for collection of baseline data and were subsequently r and omised . Intervention 4.5 hour training programme promoting an obesity management model . Main outcome measures Difference in weight between patients in intervention and control groups at 12 months ( main outcome measure ) and at 3 months and 18 months ; change in practitioners ' knowledge and behaviour in obesity management consultations . Results Twelve months after training the patients in the intervention group were 1 ( 95 % confidence interval - 1.9 to 3.9 ) kg heavier than controls ( P = 0.5 ) . Some evidence indicated that practitioners ' knowledge had improved . Some aspects of the management model , including recording weight , target weight , and dietary targets , occurred more frequently in intervention practice s after the training , but in absolute terms levels of implementation were low . Conclusion A training package promoting a brief , prescriptive approach to the treatment of obesity through lifestyle modification , intended to be incorporated into routine clinical practice , did not ultimately affect the weight of this motivated and at risk cohort of patients BACKGROUND Healthcare costs attributable to obesity have previously involved estimations based on costs of diseases commonly considered as having obesity as an underlying factor . AIM To quantify the impact of obesity on total primary care drug prescribing . DESIGN OF STUDY Review of computer generated and h and written prescriptions to determine total prescribing volume for all drug classes . SETTING Twenty-three general practice surgeries in the UK . METHOD Stratified r and om selection of 1150 patients who were obese ( body mass index [ BMI ] > 30 kg/m(2 ) ) and 1150 age and sex-matched controls of normal weight ( BMI 18.5-<25 kg/m(2 ) ) . Retrospective review of medical records over an 18-month period . RESULTS A higher percentage of patients who were obese , compared with those of normal weight , were prescribed at least one drug in the following disease categories : cardiovascular ( 36 % versus 20 % ) , central nervous system ( 46 % versus 35 % ) , endocrine ( 26 % versus 18 % ) , and musculoskeletal and joint disease ( 30 % versus 22 % ) . All of these categories had a P-value of < 0.001 . Other categories , such as gastrointestinal ( 24 % versus 18 % ) , infections ( 42 % versus 35 % ) , skin ( 24 % versus 19 % ) had a P-value of < 0.01 , while respiratory diseases ( 18 % versus 21 % ) had a P-value of < 0.05 . Total prescribing volume was significantly higher for the group with obesity and was increased in the region of two- to fourfold in a wide range of prescribing categories : ulcer healing drugs , lipid regulators , beta-adrenoreceptor drugs , drugs affecting the rennin angiotensin system , calcium channel blockers , antibacterial drugs , sulphonylureas , biguanides , non-steroidal anti-inflammatories ( NSAIDs ) ( P<0.001 ) and fibrates , angiotensin II antagonists , and thyroid drugs ( P<0.05 ) . The main impact on prescribing volumes is from numbers of patients treated , although in some areas there is an effect from greater dosage or longer treatment in those who are obese including calcium channel blockers , antihistamines , hypnotics , drugs used in the treatment of nausea and vertigo , biguanides , and NSAIDs ( P<0.05 ) reflected in significantly increased defined daily dose prescribing . CONCLUSIONS This large study of contemporary practice indicates that obesity more than doubled prescribing in most drug categories Background Obesity affects 25 % of the UK adult population but modest weight loss can reduce the incidence of obesity-related chronic disease . Some effective weight loss treatments exist but there is no nationally available National Health Service ( NHS ) treatment service , and general practitioners ( GPs ) rarely discuss weight management with patients or support behavior change . Evidence shows that commercial weight management services , that most primary care trusts have ' on prescription ' , are more effective than primary care treatment . Methods / design We propose a controlled trial where patients will be r and omized to receive either the offer of help by referral to a weight management service and follow-up to assess progress , or advice to lose weight on medical grounds . The primary outcome will be weight change at 12-months . Other questions are : what actions do people take to manage their weight in response to the two GP intervention types ? How do obese patients feel about GPs opportunistically discussing weight management and how does this vary by intervention type ? How do GPs feel about raising the issue opportunistically and giving the two types of brief intervention ? What is the cost per kg/m2 lost for each intervention ? Research assistants visiting GP practice s in Engl and ( n = 60 ) would objective ly measure weight and height prior to GP consultations and r and omize willing patients ( body mass index 30 + , excess body fat , 18 + years ) using sealed envelopes . Full recruitment ( n = 1824 ) is feasible in 46 weeks , requiring six sessions of advice-giving per GP . Participants will be contacted at 3 months ( postintervention ) via telephone to identify actions they have taken to manage their weight . We will book appointments for participants to be seen at their GP practice for a 12-month follow-up . Discussion Trial results could make the case for brief interventions for obese people consulting their GP and introduce widespread simple treatments akin to the NHS Stop Smoking Service . Likewise , the intervention could be introduced in the Quality and Outcomes Framework and influence practice worldwide . Trial registration Current Controlled Trials IS RCT N26563137 Forty smokers and 47 overweight individuals were recruited for a home correspondence program for either smoking cessation or weight loss . Participants were assigned to one of four programs for changing their respective health behaviors : ( 1 ) a home correspondence program conducted entirely by mail , ( 2 ) the mail program with supplemental financial contigency contracts tied to completion of written homework , ( 3 ) the correspondence programs supplemented both by homework contracts and by regular calls to a telephone answering system , and ( 4 ) a st and ard behavioral group program which acted as a comparison condition . Results showed that all three correspondence approaches produced significant changes in health behaviors equal to the changes experienced by participants in the st and ard group program . The implication of these findings for development of low cost programs for disease prevention are discussed This paper explores the role of balancing covariates between treatment groups in the design of cluster r and omized trials . General expressions are obtained for two criteria to evaluate design s for parallel group studies with two treatments . The first is the variance of the estimated treatment effect and the second is the extent to which the estimated treatment effect is changed by adjusting for covariates . It is argued that the second of these is more important for cluster r and omized trials . Methods of obtaining balanced design s from covariates which are available at the start of a study are proposed . An imbalance measure is used to compare the extent to which design s balance important covariates between the arms of a trial . Several approaches to selecting a well balanced design are possible . A method that r and omly selects one member from the class of design s with acceptable bias will allow r and omization inference as well as model-based inference . The methods are illustrated with data from a trial of school-based sex education Despite several clinical practice guidelines , there remains a considerable gap in prevention and management of obesity in primary care . To address the need for changing provider behaviour , a r and omized controlled trial with convergent mixed method evaluation , the 5As Team ( 5AsT ) study , was conducted . As part of the 5AsT intervention , the 5AsT tool kit was developed . This paper describes the development process and evaluation of these tools . Tools were co‐developed by the multidisciplinary research team and the 5AsT , which included registered nurses/nurse practitioners ( n = 15 ) , mental health workers ( n = 7 ) and registered dieticians ( n = 7 ) , who were previously r and omized to the 5AsT intervention group at a primary care network in Edmonton , Alberta , Canada . The 5AsT tool development occurred through a practice /implementation‐oriented , need‐based , iterative process during learning collaborative sessions of the 5AsT intervention . Feedback during tool development was received through field notes and final provider evaluation was carried out through anonymous question naires . Twelve tools were co‐developed with 5AsT. All tools were evaluated as either ‘ most useful ’ or ‘ moderately useful ’ in primary care practice by the 5AsT. Four key findings during 5AsT tool development were the need for : tools that were adaptive , tools to facilitate interdisciplinary practice , tools to help patients underst and realistic expectations for weight loss and shared decision‐making tools for goal setting and relapse prevention . The 5AsT tools are primary care tools which extend the utility of the 5As of obesity management framework in clinical practice STUDY OBJECTIVE : To study the clinical and cost outcomes of providing nutritional counselling to patients with one or more of the following conditions : overweight , hypertension and type 2 diabetes . DESIGN : The study was design ed as a r and om controlled trial . Consecutive patients were screened opportunistically for one or more of the above conditions and r and omly allocated to one of two intervention groups ( doctor/dietitian or dietitian ) or a control group . Both intervention groups received six counselling sessions over 12 months from a dietitian . However , in the doctor/dietitian group it was the doctor and not the dietitian who invited the patient to join the study and the same doctor also review ed progress at two of the six counselling sessions . SETTING : The study was conducted in a university group general practice set in a lower socioeconomic outer suburb of Perth , Western Australia . PATIENTS : Of the 273 patients r and omly allocated to a study group , 198 were women . Age ranged from 25 to 65 years . Seventy eight per cent of patients resided in the lower two socioecnomic quartiles , 56 per cent described their occupation as home duties and 78 per cent were partnered . RESULTS : Both intervention groups reduced weight and blood pressure compared with the control group . Patients in the doctor/dietitian group were more likely to complete the 12 month programme than those in the dietitian group . Patients in the doctor/dietitian group lost an average of 6.7 kg at a cost of $ A9.76 per kilogram , while the dietitian group lost 5.6 kg at a cost of $ A7.30 per kilogram . CONCLUSION : General practitioners , in conjunction with a dietitian , can produce significant weight and blood pressure improvement by health promotion methods Background There is a need for cost-effective weight management interventions that primary care can deliver to reduce the morbidity caused by obesity . Automated web-based interventions might provide a solution , but evidence suggests that they may be ineffective without additional human support . The main aim of this study was to carry out a feasibility trial of a web-based weight management intervention in primary care , comparing different levels of nurse support , to determine the optimal combination of web-based and personal support to be tested in a full trial . Methods This was an individually r and omised four arm parallel non-blinded trial , recruiting obese patients in primary care . Following online registration , patients were r and omly allocated by the automated intervention to either usual care , the web-based intervention only , or the web-based intervention with either basic nurse support ( 3 sessions in 3 months ) or regular nurse support ( 7 sessions in 6 months ) . The main outcome measure ( intended as the primary outcome for the main trial ) was weight loss in kg at 12 months . As this was a feasibility trial no statistical analyses were carried out , but we present means , confidence intervals and effect sizes for weight loss in each group , uptake and retention , and completion of intervention components and outcome measures . Results All r and omised patients were included in the weight loss analyses ( using Last Observation Carried Forward ) . At 12 months mean weight loss was : usual care group ( n = 43 ) 2.44 kg ; web-based only group ( n = 45 ) 2.30 kg ; basic nurse support group ( n = 44 ) 4.31 kg ; regular nurse support group ( n = 47 ) 2.50 kg . Intervention effect sizes compared with usual care were : d = 0.01 web-based ; d = 0.34 basic nurse support ; d = 0.02 regular nurse support . Two practice s deviated from protocol by providing considerable weight management support to their usual care patients . Conclusions This study demonstrated the feasibility of delivering a web-based weight management intervention supported by practice nurses in primary care , and suggests that the combination of the web-based intervention with basic nurse support could provide an effective solution to weight management support in a primary care context .Trial registration Current Controlled Trials IS RCT N31685626 In a r and omized double-blind trial , 60 obese patients were assigned in groups of 12 to five therapists . The patients for each therapist were then r and omly assigned in groups of four to placebo or one of two preparations of mazindol . Ninety-three percent of the patients completed the nine weeks of treatment . Weight loss averaged 1.1 lb per week and there was no advantage to pharmacological agents over placebo . However , there were significant differences between therapists . Weight loss by the patients assigned to physicians was no better than for those assigned to nonphysician personnel , but there were significant differences between individual nonphysician personnel . These findings support the concept that nonphysician personnel may be effective in treating many obese patients . In addition , we could not find a significant effect of either form of mazindol when compared to placebo OBJECTIVE It is unclear whether training physicians to counsel obese patients leads to weight loss . This study assessed whether a 5-h multimodal longitudinal obesity curriculum for residents on the basis of the 5As ( assess , advise , agree , assist , and arrange ) was associated with weight loss in their obese patients . DESIGN AND METHODS Twenty-three primary care internal medicine residents were assigned by rotation schedule to intervention ( curriculum ) or control groups . We then conducted follow-up chart review s to determine weight change at up to 12 months following the index visit . 158 obese patients ( 76 in the intervention group and 82 in the control group ) completed exit interviews ; 22 patients who presented for acute care at the index visit were excluded . Chart review s were conducted on the 46 patients in the intervention group and 41 patients in the control group who were seen again within 12 months of the index visit and had follow-up weight measurements . RESULTS The main outcome of interest was mean change in weight at 12 months compared between the intervention and control groups . Patients of residents in the intervention group had a mean weight loss of -1.53 kg ( s.d . = 3.72 ) although the patients of those in the control group had a mean weight gain of 0.30 kg ( s.d . = 3.60 ) , P = 0.03 . Six ( 15.8 % ) patients in the intervention group and 2 ( 5.4 % ) patients in the control group lost > 5 % body weight ( P = 0.14 ) . CONCLUSIONS Although the magnitude of weight loss was small , this study shows that training physicians to counsel patients can produce measurable patient outcomes Aims /hypothesis . The aim of the Diabetes Prevention Study is to assess the efficacy of an intensive diet-exercise programme in preventing or delaying Type II ( non-insulin-dependent ) diabetes mellitus in subjects with impaired glucose tolerance , to evaluate the effects of the intervention programme on cardiovascular risk factors and to assess the determinants for the progression to diabetes in persons with impaired glucose tolerance . Methods . A total of 523 overweight subjects with impaired glucose tolerance ascertained by two oral glucose tolerance tests were r and omised to either a control or intervention group . The control subjects received general information at the start of the trial about the lifestyle changes necessary to prevent diabetes and about annual follow-up visits . The intervention subjects had seven sessions with a nutritionist during the first year and a visit every 3 months thereafter aim ed at reducing weight , the intake of saturated fat and increasing the intake of dietary fibre . Intervention subjects were also guided individually to increase their physical activity . Results . During the first year , weight loss in the first 212 study subjects was 4.7 ± 5.5 vs 0.9 ± 4.1 kg in the intervention and control group , respectively ( p < 0.001 ) . The plasma glucose concentrations ( fasting : 5.9 ± 0.7 vs 6.4 ± 0.8 mmol/l , p < 0.001 ; and 2-h 7.8 ± 1.8 vs 8.5 ± 2.3 mmol/l , p < 0.05 ) were significantly lower in the intervention group after the first year of intervention . Favourable changes were also found in blood pressure , serum lipids and anthropometric indices in the intervention group . Conclusion /interpretation . The interim results show the efficacy and feasibility of the lifestyle intervention programme . [ Diabetologia ( 1999 ) 42 : 793–801 OBJECTIVE : To describe methods , recruitment success , and 1-y results of a study evaluating the effectiveness of phone- and mail-based weight-loss interventions in a managed care setting . DESIGN : R and omized clinical trial with three groups , that is , usual care , mail intervention , and phone intervention . SUBJECTS : In total , 1801 overweight members of a managed-care organization ( MCO ) . MEASUREMENTS : Height , weight , medical status , and weight-loss history were measured at baseline . Participation in intervention activities was monitored for 12 months in the two active treatment groups . Self-reported weight was obtained at 6 and 12 months . RESULTS : More individuals assigned to mail treatment started it ( 88 % ) than did those assigned to phone treatment ( 69 % ) . However , program completion rates were higher in the phone ( 36 % ) than mail ( 7 % ) intervention . The mean weight losses were 1.93 , 2.38 , and 1.47 kg at 6 months in the mail , phone , and usual care groups , respectively . The differences between the phone and usual care groups were statistically significant . The mean weight losses at 12 months did not differ by treatment group ( 2.28 kg mail , 2.29 kg phone , and 1.92 kg usual care ) . Greater weight loss was seen in men , older participants , and those with no prior experience in a weight-loss program . Heavier participants and those who reported current treatment for depression lost less weight . CONCLUSION : Although mail- and phone-based weight-loss programs can be delivered to large numbers of people in an MCO setting , additional work is needed to enhance their clinical efficacy as well as to assess their costs BACKGROUND The Care Of Childhood Obesity ( COCO ) clinic at the Bristol Royal Hospital for Children ( BRHC ) uses a multidisciplinary approach comprising a consultant , dietitian , and exercise specialist . The clinic has demonstrated efficacy in managing children 's weight but similar clinics are scarce in the UK . AIM This pilot r and omised controlled trial ( RCT ) aim ed to examine the feasibility of undertaking a fully powered RCT and to gauge whether the COCO model could be effective as a nurse-led clinic in primary care setting s. DESIGN AND SETTING Patients were r and omised to a hospital-based childhood obesity clinic or a nurse-led clinic in a primary care setting in south-west Engl and . METHOD Children aged 5 - 16 years with a body mass index ( BMI ) ≥98th centile were referred by GPs to the consultant in charge of the COCO clinic at BRHC . Referred children were clinical ly screened for suitability and invited into the study . Consenting families were r and omised to BRHC or a primary care clinic ( PCC ) and offered five appointments over 12 months . Clinical effectiveness was measured by change in body mass index st and ard deviation score ( BMI SDS ) at 12 months . Other measures included : treatment adherence , quality of life ( QOL ) , and satisfaction . Feasibility was examined by assessing referral , screening , and recruitment data . RESULTS A total 152 patients were referred by GPs : 31 ( 20 % ) were screened out ; 45 ( 30 % ) declined to participate . Seventy-six ( 50 % ) patients were r and omised and 68 provided baseline data ( PCC = 42 ; BRHC = 26 ) ; 52 provided outcome data ( PCC = 29 ; BRHC = 23 ) . Mean change in BMI SDS was PCC -0.17 ( 95 % confidence interval [ CI ] = -0.27 to -0.07 ) ; BRHC -0.15 ( 95 % CI = -0.26 to -0.05 ) . QOL , adherence , and satisfaction data indicated similar positive patterns in both trial arms . CONCLUSION Screening and recruitment data indicate that primary care is a clinical ly appropriate setting and acceptable to families . The primary clinical outcome measure ( reduction in BMI SDS ) , along with secondary outcome measures , indicate that primary care has the potential to be effective in providing weight management for children , using the COCO model This experiment evaluated the efficacy of television delivery of a behavioral weight reduction program . Seventy-one overweight adults were r and omly assigned to a live-contact weight loss group that was videotaped for viewing by other groups , a live-contact group that was not videotaped , a television-delivered group that observed the videotaped weight loss sessions , or a waiting-list control group . Participants in all 3 treatment groups lost significantly more weight during the 8-week treatment program than those in the waiting-list control group . There was no significant weight loss differences among the 3 treatment groups during the program . These weight changes were maintained at 3-month follow-up . At 15-month follow-up , the television-delivered group and the live-contact group maintained their weight losses , whereas the videotaped group did not . Cost-effectiveness analyses indicated that the television-delivered group received the most cost-effective treatment Objective To assess the effectiveness of a range of weight management programmes in terms of weight loss . Design Eight arm r and omised controlled trial . Setting Primary care trust in Birmingham , Engl and . Participants 740 obese or overweight men and women with a comorbid disorder identified from general practice records . Interventions Weight loss programmes of 12 weeks ’ duration : Weight Watchers ; Slimming World ; Rosemary Conley ; group based , dietetics led programme ; general practice one to one counselling ; pharmacy led one to one counselling ; choice of any of the six programmes . The comparator group was provided with 12 vouchers enabling free entrance to a local leisure ( fitness ) centre . Main outcome measures The primary outcome was weight loss at programme end ( 12 weeks ) . Secondary outcomes were weight loss at one year , self reported physical activity , and percentage weight loss at programme end and one year . Results Follow-up data were available for 658 ( 88.9 % ) participants at programme end and 522 ( 70.5 % ) at one year . All programmes achieved significant weight loss from baseline to programme end ( range 1.37 kg ( general practice ) to 4.43 kg ( Weight Watchers ) ) , and all except general practice and pharmacy provision result ed in significant weight loss at one year . At one year , only the Weight Watchers group had significantly greater weight loss than did the comparator group ( 2.5 ( 95 % confidence interval 0.8 to 4.2 ) kg greater loss , ) . The commercial programmes achieved significantly greater weight loss than did the primary care programmes at programme end ( mean difference 2.3 ( 1.3 to 3.4 ) kg ) . The primary care programmes were the most costly to provide . Participants allocated to the choice arm did not have better outcomes than those r and omly allocated to a programme . Conclusions Commercially provided weight management services are more effective and cheaper than primary care based services led by specially trained staff , which are ineffective . Trial registration Current Controlled Trials IS RCT N25072883 Background The majority of obese subjects are treated by primary care physicians ( PCPs ) who often feel uncomfortable with the management of obesity . In a previous study , we successfully developed , implemented and evaluated an obesity management system based on training and coaching of health professionals of family medicine groups ( FMGs ) by a team of experts in obesity management . Using a pre/post design , this study suggested a positive impact on health professionals ’ perceptions and reported obesity care . The current research project is aim ed at evaluating the impact on obesity screening and care of this integrated obesity management system . We hypothesize that our program combining preceptorships with a virtual community and on-site coaching will improve : ( 1 ) management and weight loss of obese/overweight subjects treated by PCPs for hypertension , type 2 diabetes or impaired glucose tolerance ; and ( 2 ) screening and initial management of obesity among a regular follow-up group of patients of PCPs who practice in FMGs . Methods / Design Ten FMGs will be approached for a practice monitoring project and will be r and omised to receive the intervention developed in our previous project or will only be provided clinical practice guidelines . In the participating FMGs , we will enrol 22 patients per FMG with weight related targeted disease and 24 patients with regular follow-up . These patients will be evaluated for the care they received regarding screening and /or management of obesity using medical chart review s , and will fill out a question naire on their lifestyle and satisfaction . They will also be examined for anthropometric measures , vital signs , blood markers for chronic diseases and physical fitness . The same patients will be assessed again after 18 months . The impact of the program on health professionals will be evaluated at baseline , and at 1 year . Qualitative data will also be collected from both professional and patient participants . Direct and indirect costs and QALYs will be evaluated as indicators of cost-effectiveness . Discussion In the context of the dramatic increase in obesity prevalence and the low perception of PCPs ’ self-efficacy , providing efficient strategies to PCPs and interdisciplinary health care teams for management of obesity is crucial . Trial registration Clinical trials.gov Identifier : The Consoli date d St and ards of Reporting Trials ( CONSORT ) statement was developed to improve the reporting of r and omised controlled trials . It was initially published in 1996 and focused on the reporting of parallel group r and omised controlled trials . The statement was revised in 2001 , with a further up date in 2010 . A separate CONSORT statement for the reporting of abstract s was published in 2008 . In earlier papers we considered the implication s of the 2001 version of the CONSORT statement for the reporting of cluster r and omised trial . In this paper we provide up date d and extended guidance , based on the 2010 version of the CONSORT statement and the 2008 CONSORT statement for the reporting of abstract s. BACKGROUND AND OBJECTIVES Obesity is a common problem that increases risk of many other diseases , from heart disease to cancer . While counseling by a physician increases patient report of weight loss attempts and increased exercise , primary care physicians do not frequently address obesity . The objectives of this study were to determine how often obesity was included on the problem list and whether adding obesity to the problem list affected the rate at which it was addressed in future visits . METHODS We conducted an initial assessment , followed by a r and omized controlled trial of patient records at a family medicine residency office . The intervention was the addition of obesity to the problem list . The measured outcome was whether or not obesity was listed as an encounter diagnosis in the following 5 months . RESULTS At baseline , 36.2 % of obese patients had obesity on their problem list . A total of 55.5 % of these patients had obesity addressed by a provider in the past year , compared with 5.1 % of patients who did not have obesity on their problem list . In the 5 months following the intervention , 38 ( 14.7 % ) of the 258 patients in the intervention group had obesity addressed , compared with 11 ( 4.6 % ) of the 239 patients in the control group . CONCLUSIONS There is a significant relationship between the addition of obesity to the problem list and providers addressing obesity at future visits . This simple intervention could be accomplished automatically by the EMR and has the potential to change provider behavior CONTEXT Weight loss using low-calorie diets produces variable results , presumably due to a wide range of energy deficits and low-dietary adherence . OBJECTIVE Our objective was to quantify the relationship between dietary adherence , weight loss , and severity of caloric restriction . DESIGN AND SETTING Participants were r and omized to diet only , diet-endurance training , or diet-resistance training until body mass index ( BMI ) was less than 25 kg/m(2 ) . PARTICIPANTS Healthy overweight ( BMI 27 - 30 ) premenopausal women ( n = 141 ) were included in the study . INTERVENTIONS An 800-kcal/d(-1 ) diet was provided , and the exercise groups were engaged in three sessions per week . MAIN OUTCOMES Dietary adherence , calculated from total energy expenditure determined by doubly labeled water measurements and dual-energy x-ray absorptiometry body composition changes , and degree of caloric restriction were determined . RESULTS All groups had similar weight loss ( approximately 12.1 + /- 2.5 kg ) and length of time to reach target BMI ( approximately 158 + /- 70 d ) . Caloric restriction averaged 59 + /- 9 % , and adherence to diet was 73 + /- 34 % . Adherence to diet was inversely associated to days to reach target BMI ( r = -0.687 ; P < 0.01 ) and caloric restriction ( r = -0.349 ; P < 0.01 ) . Association between adherence to diet and percent weight lost as fat was positive for the diet-endurance training ( r = 0.364 ; P < 0.05 ) but negatively correlated for the diet-only group ( r = -0.387 ; P < 0.05 ) . CONCLUSIONS Dietary adherence is strongly associated with rates of weight loss and adversely affected by the severity of caloric restriction . Weight loss programs should consider moderate caloric restriction relative to estimates of energy requirements , rather than generic low-calorie diets BACKGROUND The obesity epidemic has spared no age group , even young infants . Most childhood obesity is incident by the age of 5 years , making prevention in preschool years a priority . OBJECTIVE To examine 2-year changes in age- and sex-specific BMI z-scores and obesity-related behaviours among 441 of the 475 originally recruited participants in High Five for Kids , a cluster r and omized controlled trial in 10 paediatric practice s. METHODS The intervention included a more intensive 1-year intervention period ( four in-person visits and two phone calls ) followed by a less intensive 1-year maintenance period ( two in-person visits ) among children who were overweight or obese and age 2 - 6 years at enrolment . The five intervention practice s restructured care to manage these children including motivational interviewing and educational modules targeting television viewing and intakes of fast food and sugar-sweetened beverages . RESULTS After 2 years , compared with usual care , intervention participants had similar changes in BMI z-scores ( -0.04 units ; 95 % CI -0.14 , 0.06 ) , television viewing ( -0.20 h/d ; -0.49 to 0.09 ) and intakes of fast food ( -0.09 servings/week ; -0.34 to 0.17 ) and sugar-sweetened beverages ( -0.26 servings/day ; -0.67 to 0.14 ) . CONCLUSION High Five for Kids , a primarily clinical -based intervention , did not affect BMI z-scores or obesity-related behaviours after 2 years OBJECTIVE To describe the 1 ) lifestyle intervention used in the Finnish Diabetes Prevention Study , 2 ) short- and long-term changes in diet and exercise behavior , and 3 ) effect of the intervention on glucose and lipid metabolism . RESEARCH DESIGN AND METHODS There were 522 middle-aged , overweight subjects with impaired glucose tolerance who were r and omized to either a usual care control group or an intensive lifestyle intervention group . The control group received general dietary and exercise advice at baseline and had an annual physician 's examination . The subjects in the intervention group received additional individualized dietary counseling from a nutritionist . They were also offered circuit-type resistance training sessions and advised to increase overall physical activity . The intervention was the most intensive during the first year , followed by a maintenance period . The intervention goals were to reduce body weight , reduce dietary and saturated fat , and increase physical activity and dietary fiber . RESULTS The intervention group showed significantly greater improvement in each intervention goal . After 1 and 3 years , weight reductions were 4.5 and 3.5 kg in the intervention group and 1.0 and 0.9 kg in the control group , respectively . Measures of glycemia and lipemia improved more in the intervention group . CONCLUSIONS The intensive lifestyle intervention produced long-term beneficial changes in diet , physical activity , and clinical and biochemical parameters and reduced diabetes risk . This type of intervention is a feasible option to prevent type 2 diabetes and should be implemented in the primary health care system Background Obesity is a pressing public health concern , which frequently presents in primary care . With the explosive obesity epidemic , there is an urgent need to maximize effective management in primary care . The 5As of Obesity Management ™ ( 5As ) are a collection of knowledge tools developed by the Canadian Obesity Network . Low rates of obesity management visits in primary care suggest provider behaviour may be an important variable . The goal of the present study is to increase frequency and quality of obesity management in primary care using the 5As Team ( 5AsT ) intervention to change provider behaviour . Methods / design The 5AsT trial is a theoretically informed , pragmatic r and omized controlled trial with mixed methods evaluation . Clinic-based multidisciplinary teams ( RN/NP , mental health , dietitians ) will be r and omized to control or the 5AsT intervention group , to participate in biweekly learning collaborative sessions supported by internal and external practice facilitation . The learning collaborative content addresses provider-identified barriers to effective obesity management in primary care . Evidence -based shared decision making tools will be co-developed and iteratively tested by practitioners . Evaluation will be informed by the RE- AIM framework . The primary outcome measure , to which participants are blinded , is number of weight management visits/full-time equivalent ( FTE ) position . Patient-level outcomes will also be assessed , through a longitudinal cohort study of patients from r and omized practice s. Patient outcomes include clinical ( e.g. , body mass index [ BMI ] , blood pressure ) , health-related quality of life ( SF-12 , EQ5D ) , and satisfaction with care . Qualitative data collected from providers and patients will be evaluated using thematic analysis to underst and the context , implementation and effectiveness of the 5AsT program . Discussion The 5AsT trial will provide a wide range of insights into current practice s , knowledge gaps and barriers that limit obesity management in primary practice . The use of existing re sources , collaborative design , practice facilitation , and integrated feedback loops cultivate an applicable , adaptable and sustainable approach to increasing the quantity and quality of weight management visits in primary care . Trial registration NCT01967797 Increasingly , research is directed at advancing methods to address obesity management in primary care . In this paper we describe the role of interdisciplinary collaboration , or lack thereof , in patient weight management within 12 teams in a large primary care network in Alberta , Canada . Qualitative data for the present analysis were derived from the 5As Team ( 5AsT ) trial , a mixed‐ method r and omized control trial of a 6‐month participatory , team‐based educational intervention aim ed at improving the quality and quantity of obesity management encounters in primary care practice . Participants ( n = 29 ) included in this analysis are healthcare providers supporting chronic disease management in 12 family practice clinics r and omized to the intervention arm of the 5AsT trial including mental healthcare workers ( n = 7 ) , registered dietitians ( n = 7 ) , registered nurses or nurse practitioners ( n = 15 ) . Participants were part of a 6‐month intervention consisting of 12 biweekly learning sessions aim ed at increasing provider knowledge and confidence in addressing patient weight management . Qualitative methods included interviews , structured field notes and logs . Four common themes of importance in the ability of healthcare providers to address weight with patients within an interdisciplinary care team emerged , ( i ) Availability ; ( ii ) Referrals ; ( iii ) Role perception and ( iv ) Messaging . However , we find that what was key to our participants was not that these issues be uniformly agreed upon by all team members , but rather that communication and clinic relationships support their continued negotiation . Our study shows that firm clinic relationships and deliberate communication strategies are the foundation of interdisciplinary care in weight management . Furthermore , there is a clear need for shared messaging concerning obesity and its treatment between members of interdisciplinary teams Background Tailoring is a frequent component of approaches for implementing clinical practice guidelines , although evidence on how to maximise the effectiveness of tailoring is limited . In Engl and , overweight and obesity are common , and national guidelines have been produced by the National Institute for Health and Care Excellence . However , the guidelines are not routinely followed in primary care . Methods A tailored implementation intervention was developed following an analysis of the determinants of practice influencing the implementation of the guidelines on obesity and the selection of strategies to address the determinants . General practice s in the East Midl and s of Engl and were invited to take part in a cluster r and omised controlled trial of the intervention . The primary outcome measure was the proportion of overweight or obese patients offered a weight loss intervention . Secondary outcomes were the proportions of patients with ( 1 ) a BMI or waist circumference recorded , ( 2 ) record of lifestyle assessment , ( 3 ) referred to weight loss services , and ( 4 ) any change in weight during the study period . We also assessed the mean weight change over the study period . Follow-up was for 9 months after the intervention . A process evaluation was undertaken , involving interviews of sample s of participating health professionals . Results There were 16 general practice s in the control group , and 12 in the intervention group . At follow-up , 15.08 % in the control group and 13.19 % in the intervention group had been offered a weight loss intervention , odds ratio ( OR ) 1.16 , 95 % confidence interval ( CI ) ( 0.72 , 1.89 ) . BMI /waist circumference measurement 42.71 % control , 39.56 % intervention , OR 1.15 ( CI 0.89 , 1.48 ) , referral to weight loss services 5.10 % control , 3.67 % intervention , OR 1.45 ( CI 0.81 , 2.63 ) , weight management in the practice 9.59 % control , 8.73 % intervention , OR 1.09 ( CI 0.55 , 2.15 ) , lifestyle assessment 23.05 % control , 23.86 % intervention , OR 0.98 ( CI 0.76 , 1.26 ) , weight loss of at least 1 kg 42.22 % control , 41.65 % intervention , OR 0.98 ( CI 0.87 , 1.09 ) . Health professionals reported the interventions as increasing their confidence in managing obesity and providing them with practical re sources . Conclusions The tailored intervention did not improve the implementation of the guidelines on obesity , despite systematic approaches to the identification of the determinants of practice . The methods of tailoring require further development to ensure that interventions target those determinants that most influence implementation . Trial registration IS RCT Background Obstructive sleep apnea ( OSA ) and hypertension are well-known cardiovascular risk factors . Their control could reduce the burden of heart disease across population s. Several drugs are used to control hypertension , but the only consistently effective treatment of OSA is continuous positive airway pressure . The identification of a drug capable of improving OSA and hypertension simultaneously would provide a novel approach in the treatment of both diseases . Methods / Design This is a r and omized double-blind clinical trial , comparing the use of chlorthalidone with amiloride versus amlodipine as a first drug option in patients older than 40 years of age with stage I hypertension ( 140 to 159/90 to 99 mmHg ) and moderate OSA ( 15 to 30 apneas/hour of sleep ) . The primary outcomes are the variation of the number of apneas per hour and blood pressure measured by ambulatory blood pressure monitoring . The secondary outcomes are adverse events , somnolence scale ( Epworth ) , ventilatory parameters and C reactive protein levels . The follow-up will last 8 weeks . There will be 29 participants per group . The project has been approved by the ethics committee of our institution . Discussion The role of fluid retention in OSA has been known for several decades . The use of diuretics are well established in treating hypertension but have never been appropriately tested for sleep apnea . As well as testing the efficacy of these drugs , this study will help to underst and the mechanisms that link hypertension and sleep apnea and their treatment . Trial registration Clinical Trials.gov : Background . The aim was to evaluate the effects of a 12-week , Facebook-delivered lifestyle counselling intervention , with or without physical activity self-monitoring , on physical activity and body mass index ( BMI ) in overweight and obese 13–16-year-old adolescents . Methods . Three-arm r and omized controlled trial . Participants ( n = 46 ) were r and omly assigned to intervention and control groups : one group received Facebook-delivered lifestyle counselling and monitoring of their physical activity ( Fb + Act , n = 15 ) , whereas a second experimental group received the same Facebook-delivered lifestyle counselling without self-monitoring ( Fb , n = 16 ) and a third group served as the control group ( n = 15 ) . Objective and self-reported physical activity assessment were used . Nonparametric statistical tests were used . Results . There were no significant intervention effects in terms of changes in physical activity levels or BMI from baseline to the 12-week postintervention measurements between the intervention and control groups . The Fb + Act group had lower sedentary time on weekdays compared to the control group during postintervention measurements ( p = 0.021 ) , but there was no interaction between time and group . Conclusions . Interventions were not effective at increasing physical activity in overweight and obese adolescents . Before implementing such interventions , more evaluations on their effectiveness are needed . This trial is registered with Clinical Trials.gov identifier NCT02295761 ( 2014 - 11 - 17 ) The 5As Team study was design ed to create , implement and evaluate a flexible intervention to improve the quality and quantity of weight management visits in primary care . The objective of this portion of the study was to explore how primary care providers incorporate weight management in their practice . 5AsT is a r and omized controlled trial ( RCT ) on the implementation of a 6‐month 5 As Team ( 5AsT ) intervention design ed to operationalize the 5As of obesity management in primary care . Data for the qualitative portion of the study presented here included semi‐structured interviews with 29 multidisciplinary team providers and field notes of intervention sessions . Thematic analysis was undertaken . A key pattern that emerged from the data was that healthcare providers usually do not address obesity as a primary focus for a visit . Rather , obesity is embedded in a wide range of primary care encounters for other conditions . Implication s were it can take extra time to discuss weight , it can be inappropriate to bring up weight as a topic , and treating risk factors and root causes of obesity have indirect benefits to patient weight management . Our findings have implication s for obesity treatment approaches and tools that assume a discreet weight management visit . The embedded nature of obesity management in primary care can be harnessed to leverage multiple opportunities for asking and assessing root causes of obesity , and working longitudinally towards individual health goals BACKGROUND AND OBJECTIVE : Few studies have tested the impact of motivational interviewing ( MI ) delivered by primary care providers on pediatric obesity . This study tested the efficacy of MI delivered by providers and registered dietitians ( RDs ) to parents of overweight children aged 2 through 8 . METHODS : Forty-two practice s from the Pediatric Research in Office Setting s Network of the American Academy of Pediatrics were r and omly assigned to 1 of 3 groups . Group 1 ( usual care ) measured BMI percentile at baseline and 1- and 2-year follow-up . Group 2 ( provider only ) delivered 4 MI counseling sessions to parents of the index child over 2 years . Group 3 ( provider + RD ) delivered 4 provider MI sessions plus 6 MI sessions from a RD . The primary outcome was child BMI percentile at 2-year follow up . RESULTS : At 2-year follow-up , the adjusted BMI percentile was 90.3 , 88.1 , and 87.1 for groups 1 , 2 , and 3 , respectively . The group 3 mean was significantly ( P = .02 ) lower than group 1 . Mean changes from baseline in BMI percentile were 1.8 , 3.8 , and 4.9 across groups 1 , 2 , and 3 . CONCLUSIONS : MI delivered by providers and RDs ( group 3 ) result ed in statistically significant reductions in BMI percentile . Research is needed to determine the clinical significance and persistence of the BMI effects observed . How the intervention can be brought to scale ( in particular , how to train physicians to use MI effectively and how best to train RDs and integrate them into primary care setting s ) also merits future research Background In the UK around 22 % of men and 24 % of women are obese , and there are varying but worrying levels in other European countries . Obesity is a chronic condition that carries an important health risk . National guidelines , for use in Engl and , on the management of people who are overweight or obese have been published by the National Institute for Health and Clinical Excellence ( NICE , 2006 ) . NICE recommendations for primary care teams are : determine the degree of overweight and obesity ; assess lifestyle , comorbidities and willingness to change ; offer multicomponent management of overweight and obesity ; referral to external services when appropriate . This study investigates a tailored intervention to improve the implementation of these recommendations by primary care teams . Methods / Design The study is a cluster r and omised controlled trial . Primary care teams will be recruited from the East Midl and s of Engl and , and r and omised into two study arms : 1 ) the study group , in which primary care teams are offered a set of tailored interventions to help implement the NICE guidelines for overweight and obesity ; or 2 ) the control group in which primary care teams continue to practice usual care . The primary outcome is the proportion of overweight or obese patients for whom the primary care team adheres to the NICE guidelines . Secondary outcomes include the proportion of patients with a record of lifestyle assessment , referral to external weight loss services , the proportion of obese patients who lose weight during the intervention period , and the mean weight change over the same period . Discussion Although often recommended , the methods of tailoring implementation interventions to account for the determinants of practice are not well developed . This study is part of a programme of studies seeking to develop the methods of tailored implementation . Trial registration Current Controlled Trials IS RCT N07457585 . Registered 09/08/2013 . R and omisation commenced 30/08/2013 BACKGROUND Effective primary care practice ( PCP ) treatments are needed for extreme obesity . The Louisiana Obese Subjects Study ( LOSS ) tested whether , with brief training , PCPs could effectively implement weight loss for individuals with a body mass index ( BMI ) ( calculated as weight in kilograms divided by height in meters squared ) of 40 to 60 . METHODS The LOSS , a 2-year ( July 5 , 2005 , through January 30 , 2008 ) r and omized , controlled , " pragmatic clinical trial " trained 7 PCPs and 1 research clinic in obesity management . Primary outcome measure was year-2 percentage change from baseline weight . Volunteers ( 597 ) were screened and r and omized to intensive medical intervention ( IMI ) ( n = 200 ) or usual care condition ( UCC ) ( n = 190 ) . The UCC group had instruction in an Internet weight management program . The IMI group recommendations included a 900-kcal liquid diet for 12 weeks or less , group behavioral counseling , structured diet , and choice of pharmacotherapy ( sibutramine hydrochloride , orlistat , or diethylpropion hydrochloride ) during months 3 to 7 and continued use of medications and maintenance strategies for months 8 to 24 . RESULTS The mean age of participants was 47 years ; 83 % were women , and 75 % were white . Retention rates were 51 % for the IMI group and 46 % for the UCC group ( P = .30 ) . After 2 years , the results were as follows : ( 1 ) among 390 r and omized participants , 31 % in the IMI group achieved a 5 % or more weight loss and 7 % achieved a 20 % weight loss or more , compared with 9 % and 1 % of those in the UCC group . ( 2 ) The mean + /- SEM baseline observation carried forward analysis showed a weight loss of -4.9 % + /- 0.8 % in IMI and -0.2 + /- 0.3 % in UCC . ( 3 ) Last observation carried forward analysis showed a weight loss of -8.3 % + /- 0.79 % for IMI , whereas UCC was -0.0 % + /- 0.4 % . ( 4 ) A total of 101 IMI completers lost -9.7 % + /- 1.3 % ( -12.7 + /- 1.7 kg ) , whereas 89 UCC completers lost -0.4 % + /- 0.7 % ( -0.5 + /- 0.9 kg ) ; ( P < .001 for all group differences ) . Many metabolic parameters improved . CONCLUSION Primary care practice s can initiate effective medical management for extreme obesity ; future efforts must target improving retention and weight loss maintenance . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00115063 BACKGROUND Type 2 diabetes mellitus is increasingly common , primarily because of increases in the prevalence of a sedentary lifestyle and obesity . Whether type 2 diabetes can be prevented by interventions that affect the lifestyles of subjects at high risk for the disease is not known . METHODS We r and omly assigned 522 middle-aged , overweight subjects ( 172 men and 350 women ; mean age , 55 years ; mean body-mass index [ weight in kilograms divided by the square of the height in meters ] , 31 ) with impaired glucose tolerance to either the intervention group or the control group . Each subject in the intervention group received individualized counseling aim ed at reducing weight , total intake of fat , and intake of saturated fat and increasing intake of fiber and physical activity . An oral glucose-tolerance test was performed annually ; the diagnosis of diabetes was confirmed by a second test . The mean duration of follow-up was 3.2 years . RESULTS The mean ( + /-SD ) amount of weight lost between base line and the end of year 1 was 4.2+/-5.1 kg in the intervention group and 0.8+/-3.7 kg in the control group ; the net loss by the end of year 2 was 3.5+/-5.5 kg in the intervention group and 0.8+/-4.4 kg in the control group ( P<0.001 for both comparisons between the groups ) . The cumulative incidence of diabetes after four years was 11 percent ( 95 percent confidence interval , 6 to 15 percent ) in the intervention group and 23 percent ( 95 percent confidence interval , 17 to 29 percent ) in the control group . During the trial , the risk of diabetes was reduced by 58 percent ( P<0.001 ) in the intervention group . The reduction in the incidence of diabetes was directly associated with changes in lifestyle . CONCLUSIONS Type 2 diabetes can be prevented by changes in the lifestyles of high-risk subjects OBJECTIVE To examine referral by primary care providers ( PCPs ) of preschool children with obesity ( ≥95th percentile for body mass index [ BMI ] ) to a weight management intervention when offered through a r and omized clinical trial ( RCT ) , and identify reasons for not referring children . STUDY DESIGN In phase I , 3 experts in obesity , psychology , and nutrition completed an open card sort and classified PCPs ' reasons for declining referral into groups based on similarity of reasons . Categories were then defined and labeled . In phase II , 2 independent sorters placed each decline into 1 of the categories defined in phase I. RESULTS PCPs referred 78 % of eligible children to the RCT . Compared with children declined for referral , referred children had a significantly higher weight ( 48.4 lb vs 46.1 lb ; P < .001 ) and BMI percentile ( 97.6 vs 97.0 ; P < .001 ) . Eleven categories for decline were identified in phase I. In phase II , excellent reliability was obtained between each independent sorter and the phase I categories , and also between the 2 independent sorters ( κ values , 0.72 - 1.0 ) . The most common reason for declining was " family not a good fit " ( 23.6 % ) , followed by " does n't believe weight is a problem " ( 13.9 % ) , " family would not be interested " ( 12 % ) , and " does n't believe measurement is accurate " ( 11.5 % ) . Appropriately , exclusionary criteria of the RCT was a reason as well ( 11.8 % ) . CONCLUSION The availability of weight management for preschoolers through RCTs appeared to overcome barriers of re sources , time , and credible treatment cited in previous studies . However , concerns about the family 's response or interest in a weight management program remained barriers , as did PCPs ' perceptions about obesity in young children . TRIAL REGISTRATION Clinical Trials.gov : NCT01546727 OBJECTIVE To determine whether a tailored weight management program , addressing the needs of obese , low-income African-American women , would produce greater weight loss than st and ard medical care . RESEARCH METHODS AND PROCEDURES A r and omized , controlled trial was conducted between 1999 and 2003 with 144 overweight or obese women ( predominantly African-American ) enrolled at two primary care clinics . Four physicians at each clinic were r and omly assigned to provide either tailored weight management interventions or st and ard care . The tailored condition consisted of six monthly outpatient visits lasting approximately 15 minutes each , which included personalized material s and messages . The main outcome was body weight change . RESULTS The intervention group lost more weight than the st and ard care group ( p = 0.03 ) . The tailored group lost a mean ( st and ard deviation ) of 2.0 ( 3.2 ) kg by Month 6 . The st and ard care group gained 0.2 ( 2.9 ) kg . More participants in the tailored group lost weight ( 79 % vs. 47 % ; p = 0.04 ) . DISCUSSION Obese , low-income , African-American women provided with 90 minutes of physician-delivered , tailored weight management instruction over 6 months achieved greater weight loss than those receiving st and ard medical care . The primary care physician can be effective in delivering weight loss interventions , and the primary care clinic may be a useful setting to implement weight management interventions The aim of this paper is to describe the design features and practicalities of conducting a cluster r and omized trial of obesity management in primary care . The aim of the trial is to assess the effectiveness of an obesity management educational intervention delivered to staff within primary care practice s ( unit of r and omization ) in terms of change in body weight of their patients ( unit of analysis ) at one year . The design features which merit particular attention in this cluster r and omized trial include st and ardization of intervention , sample size considerations , recruitment of patients prior to r and omization of practice s , method of r and omization to balance control and intervention practice s with respect to practice and patient level characteristics , and blinding of outcome assessment . The practical problems ( and our solutions ) associated with implementing these design features , particularly those that result in a time delay between baseline data collection , r and omization and intervention , are discussed BACKGROUND / AIMS Primary care is expected to develop strategies to manage obese patients as part of coronary heart disease and diabetes national service frameworks . Little is known about current management practice s for obesity in this setting . The aim of this study is to examine current approaches to obesity management in UK primary care and to identify potential gaps in care . METHOD A total of 141 general practitioners ( GPs ) and 66 practice nurses ( PNs ) from 40 primary care practice s participated in structured interviews to examine clinician self-reported approaches to obesity management . Medical records were also review ed for 100 r and omly selected obese patients from each practice [ body mass index ( BMI ) > /=30 kg m(-2 ) , n = 4000 ] to review rates of diet counselling , dietetic or obesity centre referrals , and use of anti-obesity medication . Computerized medical records for the total practice population ( n = 206 341 , 18 - 75 years ) were search ed to examine the proportion of patients with a weight/ BMI ever recorded . RESULTS Eighty-three per cent of GPs and 97 % of PNs reported that they would raise weight as an issue with obese patients ( P < 0.01 ) . Few GPs ( 15 % ) reported spending up to 10 min in a consultation discussing weight-related issues , compared with PNs ( 76 % ; P < 0.001 ) . Over 18 months , practice -based diet counselling ( 20 % ) , dietetic ( 4 % ) and obesity centre ( 1 % ) referrals , and any anti-obesity medication ( 2 % ) were recorded . BMI was recorded for 64.2 % of patients and apparent prevalence of obesity was less than expected . CONCLUSION Obesity is under-recognized in primary care even in these 40 practice s with an interest in weight management . Weight management appears to be based on brief opportunistic intervention undertaken mainly by PNs . While clinicians report the use of external sources of support , few patients are referred , with practice -based counselling being the most common intervention Objective : To compare the efficacy of a phone vs a traditional face-to-face clinic approach to achieve 10 % weight loss and weight maintenance . Design : Twenty-six week , r and omized , controlled trial . Subjects : Twenty-four men and 72 women , ages 25–68 years , with a body mass index ( BMI ) of 33.2±3.8 . Measurements : Weight loss at 12 weeks and weight maintenance at 26 weeks were the primary outcomes . Attendance , meal replacements ( MRs ) , fruits/vegetables ( F/V ) , and physical activity ( PA ) were measured weekly for process evaluation . Results : Median weight loss ( range ) from baseline at 12 weeks was significantly different for phone at 10.6 kg ( 16.6 ) or 10.4 % and clinic at 12.7 kg ( 19.9 ) or 13.7 % , and both were significantly different when compared with the control group with a weight loss of 0.25 kg ( 5.6 ) or 0.24 % . Median weight loss at 26 weeks was 12.8 kg ( 23.4 ) or 13.0 % from baseline for the phone group and 12.5 kg ( 35.2 ) or 12.6 % from baseline for the clinic group ( P>0.05 ) . Conclusion : The median weight loss for both phone and clinic groups at 12 and 26 weeks exceeded the NHLBI guideline of 10 % weight loss from baseline . The phone approach may be a viable option to the traditional weight management clinic for both service providers and participants The objective of this study was to evaluate the effects of two weight reduction programmes on moderately and severely obese subjects over a period of five years . The subjects were r and omly divided into a rehabilitation centre group ( RC group ) and a health centre group ( HC group ) . Treatment in the RC group consisted of a three-week in-patient weight reduction programme at a rehabilitation centre and in the HC group of a ten-week out-patient weight reduction course at a health centre . Treatment in both groups continued for up to 24 months with an individual follow-up at 1 - 2-month intervals by a general practitioner ( GP ) at the health centre . The subjects were 42 women and 10 men . The mean weight of women at the onset of the study was 104 kg and the mean BMI 39.5 kg/m2 and the respective means of men 121 kg and 40.1 kg/m2 . The mean age of both sexes was 40 years . In the RC group the mean weight loss at 6 , 12 and 24 months was 11.5 , 9.1 and 5.9 kg in women , and 19.0 , 18.3 and 11.2 kg in men , respectively . In the HC group the respective values were 5.5 , 4.8 and 3.2 kg in women and 12.2 , 6.7 and 2.8 kg in men . At the five-year follow-up the mean weight change from baseline was -6.8 kg in the men and $ 0.3 kg in the women of the RC group . In the HC group the mean weight returned to baseline level in both sexes . ( ABSTRACT TRUNCATED AT 250 WORDS PURPOSE Obesity is associated with a higher risk of breast cancer mortality . The gold st and ard approach to weight loss is in-person counseling , but telephone counseling may be more feasible . We examined the effect of in-person versus telephone weight loss counseling versus usual care on 6-month changes in body composition , physical activity , diet , and serum biomarkers . METHODS One hundred breast cancer survivors with a body mass index ≥ 25 kg/m(2 ) were r and omly assigned to in-person counseling ( n = 33 ) , telephone counseling ( n = 34 ) , or usual care ( UC ) ( n = 33 ) . In-person and telephone counseling included 11 30-minute counseling sessions over 6 months . These focused on reducing caloric intake , increasing physical activity , and behavioral therapy . Body composition , physical activity , diet , and serum biomarkers were measured at baseline and 6 months . RESULTS The mean age of participants was 59 ± 7.5 years old , with a mean BMI of 33.1 ± 6.6 kg/m(2 ) , and the mean time from diagnosis was 2.9 ± 2.1 years . Fifty-one percent of the participants had stage I breast cancer . Average 6-month weight loss was 6.4 % , 5.4 % , and 2.0 % for in-person , telephone , and UC groups , respectively ( P = .004 , P = .009 , and P = .46 comparing in-person with UC , telephone with UC , and in-person with telephone , respectively ) . A significant 30 % decrease in C-reactive protein levels was observed among women r and omly assigned to the combined weight loss intervention groups compared with a 1 % decrease among women r and omly assigned to UC ( P = .05 ) . CONCLUSION Both in-person and telephone counseling were effective weight loss strategies , with favorable effects on C-reactive protein levels . Our findings may help guide the incorporation of weight loss counseling into breast cancer treatment and care CONTEXT Implementation of the National Institutes of Health 's 1998 guidelines , which recommended that health care professionals advise obese patients to lose weight , required baseline data for evaluation . OBJECTIVES To describe the proportion and characteristics of obese persons advised to lose weight by their health care professional during the previous 12 months and to determine whether the advice was associated with reported attempts to lose weight . DESIGN The Behavioral Risk Factor Surveillance System , a r and om-digit telephone survey conducted in 1996 by state health departments . SETTING Population -based sample from 50 states and the District of Columbia . PARTICIPANTS A total of 12835 adults , 18 years and older , classified as obese ( body mass index > or = 30 kg/m2 ) , who had visited their physician for a routine checkup during the previous 12 months . MAIN OUTCOME MEASURES Reported advice from a health care professional to lose weight , and reported attempts to lose weight . RESULTS Forty-two percent of participants reported that their health care professional advised them to lose weight . Using multivariate logistic regression analysis , we found that the persons who were more likely to receive advice were female , middle aged , had higher levels of education , lived in the northeast , reported poorer perceived health , were more obese , and had diabetes mellitus . Persons who reported receiving advice to lose weight were significantly more likely to report trying to lose weight than those who did not ( OR , 2.79 ; 95 % CI , 2.53 - 3.08 ) . CONCLUSIONS Less than half of obese adults report being advised to lose weight by health care professionals . Barriers to counseling need to be identified and addressed BACKGROUND Evaluation for obesity management in primary care is limited , and successful outcomes are from intensive clinical trials in hospital setting s. AIM To determine to what extent measures of success seen in intensive clinical trials can be achieved in routine primary care . Primary outcome measures were weight change and percentage of patients achieving > or=5 % loss at 12 and 24 months . DESIGN OF STUDY Prospect i ve evaluation of a new continuous improvement model for weight management in primary care . SETTING Primary care , UK . METHOD Primary care practice nurses from 65 UK general practice s delivered interventions to 1906 patients with body mass index ( BMI ) > or=30 kg/m2 or > or=28 kg/m2 with obesity-related comorbidities . RESULTS Mean baseline weight was 101.2 kg ( BMI 37.1 kg/m2 ) ; 25 % of patients had BMI > or=40 kg/m2 and 74 % had > or=1 major obesity-related comorbidity . At final data capture 1419 patients were in the programme for > or=12 months , and 825 for > or=24 months . Mean weight change in those who attended and had data at 12 months ( n=642 ) was -3.0 kg ( 95 % CI=-3.5 to -2.4 kg ) and at 24 months ( n=357 ) was -2.3 kg ( 95 % CI=-3.2 to -1.4 kg ) . Among attenders at specific time-points , 30.7 % had maintained weight loss of > or=5 % at 12 months , and 31.9 % at 24 months . A total of 761 ( 54 % ) of all 1419 patients who had been enrolled in the programme for > 12 months provided data at or beyond 12 months . CONCLUSION This intervention achieves and maintains clinical ly valuable weight loss within routine primary care OBJECTIVE : To examine the impact of two styles of educational package on practice nurses ’ management of obesity . SUBJECTS AND MEASURES : A question naire was completed by 66 practice nurses concerning their obesity related beliefs and the content and style of their weight related practice s before and one month after being r and omly allocated to either the ‘ learner centred ’ group ( who received a leaflet and were invited to attend an interactive seminar ) , the ‘ expert group ’ ( who received the leaflet ) or the control group . At the one month follow up , practice nurses were also asked to give a brief question naire to five consecutive patients , who they saw for weight loss advice , concerning the content and style of the consultation . After 6 months , practice nurses , and patients were sent a question naire about their consultation style and weight loss , respectively . RESULTS : The packages had no differential effects on practice nurses ’ beliefs about obesity . However , practice nurses in the ‘ learner group ’ reported spending longer on their consultations and being more patient centred . Their patients rated themselves as more satisfied with the consultation and reported that they were offered calorie controlled diets less often . In contrast , practice nurses in the ‘ expert group ’ reported giving weight loss advice more frequently , being less patient centred and their patients reported greater confidence in , and likelihood of , weight loss and reported that they were more likely to be offered traditional weight loss interventions . The packages had no differential effects on patient weight . CONCLUSION : Practice nurses ’ and patients ' beliefs and behaviour and the style of their interactions can be changed by both expert and learner centred educational packages . The style of packages should be chosen in terms of both the available re sources and the desired outcomes BACKGROUND Lifestyle changes involving diet , behavior , and physical activity are the cornerstone of successful weight control . Incorporating meal replacements ( 1 - 2 per day ) into traditional lifestyle interventions may offer an additional strategy for overweight patients in the primary care setting . METHODS One hundred thirteen overweight premenopausal women ( mean + /- SD age , 40.4 + /- 5.5 years ; weight , 82 + /- 10 kg ; and body mass index , 30 + /- 3 kg/m(2 ) ) participated in a 1-year weight-reduction study consisting of 26 sessions . The women were r and omly assigned to 3 different traditional lifestyle-based groups : ( 1 ) dietitian-led group intervention ( 1 hour per session ) , ( 2 ) dietitian-led group intervention incorporating meal replacements ( 1 hour per session ) , or ( 3 ) primary care office intervention incorporating meal replacements with individual physician and nurse visits ( 10 - 15 minutes per visit ) . RESULTS For the 74 subjects ( 65 % ) completing 1 year , the primary care office intervention using meal replacements was as effective as the traditional dietitian-led group intervention not using meal replacements ( mean + /- SD weight loss , 4.3 % + /- 6.5 % vs 4.1 % + /- 6.4 % , respectively ) . Comparison of the dietitian-led groups showed that women using meal replacements maintained a significantly greater weight loss ( 9.1 % + /- 8.9 % vs 4.1 % + /- 6.4 % ) ( P = .03 ) . Analysis across groups showed that weight loss of 5 % to 10 % was associated with significant ( P = .01 ) reduction in percentage of body fat , body mass index , waist circumference , resting energy expenditure , insulin level , total cholesterol level , and low-density lipoprotein cholesterol level . Weight loss of 10 % or greater was associated with additional significant ( P = .05 ) improvements in blood pressure and triglyceride level . CONCLUSIONS A traditional lifestyle intervention using meal replacements can be effective for weight control and reduction in risk of chronic disease in the physician 's office setting as well as in the dietitian-led group setting Background Physicians often do not recognize when their patients are overweight and infrequently counsel them about weight loss . Objective To evaluate a set of electronic health record (EHR)-embedded tools to assist with identification and counseling of overweight patients . Design R and omized controlled trial . Participants Physicians at an academic general internal medicine clinic were r and omized to activation of the EHR tools ( n = 15 ) or to usual care ( n = 15 ) . Patients of these physicians were included in analyses if they had a body mass index ( BMI ) between 27 and 29.9 kg/m2.InterventionThe EHR tool set included : a physician point-of-care alert for overweight ( BMI 27–29 . 9 kg/m2 ) ; a counseling template to help physicians counsel patients on action plans ; and an order set to facilitate entry of overweight as a diagnosis and to order relevant patient h and outs . Main Measures Physician documentation of overweight as a problem ; documentation of weight-specific counseling ; physician perceptions of the EHR tools ; patient self-reported progress toward their goals and perspectives about counseling received . Key Results Patients of physicians receiving the intervention were more likely than those of usual care physicians to receive a diagnosis of overweight ( 22 % vs. 7 % ; p = 0.02 ) and weight-specific counseling ( 27 % vs. 15 % ; p = 0.02 ) . Most patients receiving counseling in the intervention group reported increased motivation to lose weight ( 90 % ) and taking steps toward their goal ( 93 % ) . Most intervention physicians agreed that the tool alerted them to patients they did not realize were overweight ( 91 % ) and improved the effectiveness of their counseling ( 82 % ) ; more than half ( 55 % ) reported counseling overweight patients more frequently ( 55 % ) . However , most physicians used the tool infrequently because of time barriers . Conclusions EHR-based alerts and management tools increased documentation of overweight and counseling frequency ; the majority of patients for whom the tools were used reported short-term behavior change To examine the effects of intensive patient and /or physician diabetes education on patient health outcomes , a controlled trial was conducted in which internal medicine residents and their 532 diabetic patients were r and omly assigned to : routine care ; patient education ; physician education ; or both patient and physician education . Patient outcome data were analyzed either by analysis of covariance on post intervention values ( 2-hour post-pr and ial plasma glucose [ PPG ] ; body weight [ BW ] ; blood pressure [ BP ] ; or analysis of variance conducted on change values ( fasting plasma glucose [ FPG ] and glycosylated hemoglobin [ A1Hgb ] ) . After patient education , significant improvements were observed in FPG , A1Hgb , BW , and systolic and diastolic BP . Physician education result ed in significant decreases in FPG , A1Hgb and BW . The combination of patient plus physician education result ed in the greatest improvements in patients ' health outcomes including FPG , A1Hgb , PPG , BW and diastolic BP . Adjusted systolic BPs were not significantly different in the two groups . While these physiologic improvements were statistically and probably clinical ly significant , hyperglycemia and obesity still persisted . Thus , achieving optimal patient outcomes for a chronic disease like diabetes mellitus may require a greater or more effective use of re sources than currently estimated BACKGROUND In obese adults , physicians often fail to identify obesity and recommend treatments for it . We sought to determine whether a computerized body mass index ( BMI ) chart prompt would increase the likelihood that patients of family physicians would be diagnosed with obesity and referred for obesity treatment . METHODS A total of 846 obese patients of 37 family physicians were r and omly assigned to either have a patient 's BMI chart prompt placed in their electronic medical record ( intervention group ) or not have a BMI prompt ( comparison group ) placed in the record . We then examined patient medical records for evidence of an obesity diagnosis and referral for specific obesity treatments . We also measured whether the presence of comorbidities in obese patients influenced the likelihood of diagnoses and treatments by the physicians . RESULTS Obese patients of physicians who had a BMI chart prompt in their medical records were significantly more likely than obese patients of physicians who did not receive a BMI chart prompt to receive a diagnosis of obesity ( 16.6 % versus 10.7 % ; P=.016 ) . Patients of physicians who were provided with a BMI chart prompt were also more likely than patients of physicians who did not get a chart prompt to receive a referral for diet treatment ( 14.0 % versus 7.3 % , P=.002 ) and exercise ( 12.1 % versus 7.1 % , P=.016 ) . Of the obesity comorbidities , only obstructive sleep apnea ( OSA ) was a predictor of a patient being diagnosed with obesity ( OR=.49 , 95 % CI=0.281 , 0.869 , P=.014 ) . CONCLUSIONS Inclusion of a computerized BMI chart prompt increased the likelihood that physicians would diagnose obesity in obese patients and refer them for treatment 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 OBJECTIVE To describe the theoretical basis , use , and satisfaction with Teen CHAT , an online educational intervention design ed to improve physician-adolescent communication about healthy weight . METHODS Routine health maintenance encounters between pediatricians and family practitioners and their overweight adolescent patients were audio recorded , and content was coded to summarize adherence with motivational interviewing techniques . An online educational intervention was developed using constructs from social cognitive theory and using personalized audio recordings . Physicians were r and omized to the online intervention or not , and completed post-intervention surveys . RESULTS Forty-six physicians were recruited , and 22 physicians were r and omized to view the intervention website . The educational intervention took an average of 54min to complete , and most physicians thought it was useful , that they would use newly acquired skills with their patients , and would recommend it to others . Fewer physicians thought it helped them address confidentiality issues with their adolescent patients . CONCLUSION The Teen CHAT online intervention shows potential for enhancing physician motivational interviewing skills in an acceptable and time-efficient manner . PRACTICE IMPLICATION S If found to be effective in enhancing motivational interviewing skills and changing adolescent weight-related behaviors , wide dissemination will be feasible and indicated This study tested the feasibility of a low-technology office-based approach to weight reduction in obese hypertensive patients . Family practice residents were r and omly assigned to either an experimental or a control group . Physicians in the experimental group were instructed in methods of weight reduction , which they then passed on to their patients . Patients of experimental physicians were seen monthly , their diets were discussed , and improvements were suggested . The control group patients received their usual care . After six months the experimental patients had lost significantly more weight than the controls and had significantly reduced the number of antihypertensive drugs while maintaining blood pressure control . After 12 months there was no significant difference between the two groups with respect to weight loss , blood pressure , or number of antihypertensive drugs . Experimental and control patients who lost weight had visited their physicians more frequently than those who did not and had reduced the number of antihypertensive medications they were taking . This educationally oriented intervention trial is an example of the type of research that is practical to perform in a family practice center and is applicable in family physicians ' offices IMPORTANCE Evidence of effective treatment of childhood obesity in primary care setting s is limited . OBJECTIVE To examine the extent to which computerized clinical decision support ( CDS ) delivered to pediatric clinicians at the point of care of obese children , with or without individualized family coaching , improved body mass index ( BMI ; calculated as weight in kilograms divided by height in meters squared ) and quality of care . DESIGN , SETTING , AND PARTICIPANTS We conducted a cluster-r and omized , 3-arm clinical trial . We enrolled 549 children aged 6 to 12 years with a BMI at the 95 % percentile or higher from 14 primary care practice s in Massachusetts from October 1 , 2011 , through June 30 , 2012 . Patients were followed up for 1 year ( last follow-up , August 30 , 2013 ) . In intent-to-treat analyses , we used linear mixed-effects models to account for clustering by practice and within each person . INTERVENTIONS In 5 practice s r and omized to CDS , pediatric clinicians received decision support on obesity management , and patients and their families received an intervention for self-guided behavior change . In 5 practice s r and omized to CDS + coaching , decision support was augmented by individualized family coaching . The remaining 4 practice s were r and omized to usual care . MAIN OUTCOMES AND MEASURES Smaller age-associated change in BMI and the Healthcare Effectiveness Data and Information Set ( HEDIS ) performance measures for obesity during the 1-year follow-up . RESULTS At baseline , mean ( SD ) patient age and BMI were 9.8 ( 1.9 ) years and 25.8 ( 4.3 ) , respectively . At 1 year , we obtained BMI from 518 children ( 94.4 % ) and HEDIS measures from 491 visits ( 89.4 % ) . The 3 r and omization arms had different effects on BMI over time ( P = .04 ) . Compared with the usual care arm , BMI increased less in children in the CDS arm during 1 year ( -0.51 [ 95 % CI , -0.91 to -0.11 ] ) . The CDS + coaching arm had a smaller magnitude of effect ( -0.34 [ 95 % CI , -0.75 to 0.07 ] ) . We found substantially greater achievement of childhood obesity HEDIS measures in the CDS arm ( adjusted odds ratio , 2.28 [ 95 % CI , 1.15 - 4.53 ] ) and CDS + coaching arm ( adjusted odds ratio , 2.60 [ 95 % CI , 1.25 - 5.41 ] ) and higher use of HEDIS codes for nutrition or physical activity counseling ( CDS arm , 45 % ; CDS + coaching arm , 25 % ; P < .001 compared with usual care arm ) . CONCLUSIONS AND RELEVANCE An intervention that included computerized CDS for pediatric clinicians and support for self-guided behavior change for families result ed in improved childhood BMI . Both interventions improved the quality of care for childhood obesity . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01537510 This study describes the influence of a computerized medical record summary system in three disease areas ( hypertension , obesity and renal disease ) observed in the course of a controlled , r and omized and prospect i ve study of 479 Northwestern University Clinic patients . Experimental patients , who had available automated record summaries , and control patients , who had available only the manual record , were compared on several medical tests and procedures whose yearly occurrence was considered good medical practice for this patient population , and were compared as well on several measures of outcome of medical care . Evidence suggesting better care and outcome of care among patients with computerized record summaries available is presented OBJECTIVE To examine the effectiveness of a primary care-based obesity intervention over the first year ( 6 intervention contacts ) of a planned 2-year study . DESIGN Cluster r and omized controlled trial . SETTING Ten pediatric practice s , 5 intervention and 5 usual care . PARTICIPANTS Four hundred seventy-five children aged 2 to 6 years with body mass index ( BMI ) in the 95th percentile or higher or 85th to less than 95th percentile if at least 1 parent was overweight ; 445 ( 93 % ) had 1-year outcomes . INTERVENTION Intervention practice s received primary care restructuring , and families received motivational interviewing by clinicians and educational modules targeting television viewing and fast food and sugar-sweetened beverage intake . OUTCOME MEASURES Change in BMI and obesity-related behaviors from baseline to 1 year . RESULTS Compared with usual care , intervention participants had a smaller , nonsignificant change in BMI ( -0.21 ; 95 % confidence interval [ CI ] , -0.50 to 0.07 ; P = .15 ) , greater decreases in television viewing ( -0.36 h/d ; 95 % CI , -0.64 to -0.09 ; P = .01 ) , and slightly greater decreases in fast food ( -0.16 serving/wk ; 95 % CI , -0.33 to 0.01 ; P = .07 ) and sugar-sweetened beverage ( -0.22 serving/d ; 95 % CI , -0.52 to 0.08 ; P = .15 ) intake . In post hoc analyses , we observed significant effects on BMI among girls ( -0.38 ; 95 % CI , -0.73 to -0.03 ; P = .03 ) but not boys ( 0.04 ; 95 % CI , -0.55 to 0.63 ; P = .89 ) and among participants in households with annual incomes of $ 50 000 or less ( -0.93 ; 95 % CI , -1.60 to -0.25 ; P = .01 ) but not in higher-income households ( 0.02 ; 95 % CI , -0.30 to 0.33 ; P = .92 ) . CONCLUSION After 1 year , the High Five for Kids intervention was effective in reducing television viewing but did not significantly reduce BMI This study evaluated the effectiveness of two posttreatment programs design ed to enhance the maintenance of weight loss . Eighty-five obese clients were r and omly assigned to either ( a ) behavior therapy plus a peer-support maintenance program , ( b ) behavior therapy plus a therapist-contact maintenance program , or ( c ) behavior therapy only . At a 7-month follow-up session , the therapist-contact program result ed in significantly greater maintenance of weight loss compared with the peer support and behavior therapy only conditions . However , by the time of an 18-month follow-up assessment , overall relapse rates were equivalent across conditions Objectives Prescribed medications represent a high and increasing proportion of UK health care funds . Our aim was to quantify the influence of body mass index ( BMI ) on prescribing costs , and then the potential savings attached to implementing a weight management intervention . Methods Paper and computer-based medical records were review ed for all drug prescriptions over an 18-month period for 3400 r and omly selected adult patients ( 18 - 75 years ) stratified by BMI , from 23 primary care practice s in seven UK regions . Drug costs from the British National Formulary at the time of the review were used . Multivariate regression analysis was applied to estimate the cost for all drugs and the ‘ top ten ’ drugs at each BMI point . This allowed the total and attributable prescribing costs to be estimated at any BMI . Weight loss outcomes achieved in a weight management programme ( Counterweight ) were used to model potential effects of weight change on drug costs . Anticipated savings were then compared with the cost programme delivery . Analysis was carried out on patients with follow-up data at 12 and 24 months as well as on an intention-to-treat basis . Outcomes from Counterweight were based on the observed lost to follow-up rate of 50 % , and the assumption that those patients would continue a generally observed weight gain of 1 kg per year from baseline . Results The minimum annual cost of all drug prescriptions at BMI 20 kg/m2 was £ 50.71 for men and £ 62.59 for women . Costs were greater by £ 5.27 ( men ) and £ 4.20 ( women ) for each unit increase in BMI , to a BMI of 25 ( men £ 77.04 , women £ 78.91 ) , then by £ 7.78 and £ 5.53 , respectively , to BMI 30 ( men £ 115.93 women £ 111.23 ) , then by £ 8.27 and £ 4.95 to BMI 40 ( men £ 198.66 , women £ 160.73 ) . The relationship between increasing BMI and costs for the top ten drugs was more pronounced . Minimum costs were at a BMI of 20 ( men £ 8.45 , women £ 7.80 ) , substantially greater at BMI 30 ( men £ 23.98 , women £ 16.72 ) and highest at BMI 40 ( men £ 63.59 , women £ 27.16 ) . Attributable cost of overweight and obesity accounted for 23 % of spending on all drugs with 16 % attributable to obesity . The cost of the programme was estimated to be approximately £ 60 per patient entered . Modelling weight reductions achieved by the Counterweight weight management programme would potentially reduce prescribing costs by £ 6.35 ( men ) and £ 3.75 ( women ) or around 8 % of programme costs at one year , and by £ 12.58 and £ 8.70 , respectively , or 18 % of programme costs after two years of intervention . Potential savings would be increased to around 22 % of the cost of the programme at year one with full patient retention and follow-up . Conclusion Drug prescriptions rise from a minimum at BMI of 20 kg/m2 and steeply above BMI 30 kg/m2 . An effective weight management programme in primary care could potentially reduce prescription costs and lead to substantial cost avoidance , such that at least 8 % of the programme delivery cost would be recouped from prescribing savings alone in the first year Obesity is one of the most common presenting chronic medical conditions in primary care , yet it is not adequately treated . Physicians are often reluctant to counsel patients because of their limited training in treating chronic weight problems and negative attitudes toward obese patients . This study evaluated the feasibility of training physicians to provide weight control counseling to their patients . Eleven physicians were r and omly assigned to either an obesity-counseling skills training group or to a control group . Physicians in the counseling skills group received training in behavioral and motivational weight control techniques using a five-step patient-centered model ; they were also given patient material s for use in their practice . To evaluate pretraining to posttraining changes in physician counseling behavior , independent sample s of patients with obesity were surveyed immediately after their visit to the physician 's office . Physicians in both the counseling skills training and the control groups discussed weight with 42 % to 47 % of their patients at baseline . This increased to 89 % in physicians who received training , whereas it remained at 42 % in control physicians . Scores on a counseling measure also significantly increased from a mean of 2.7 to 9.9 in the counseling group , whereas scores in the control group remained low and stable ( 2.3 and 1.9 , respectively ) . The training program was effective in improving the frequency and quality of counseling that physicians delivered to their patients with obesity . Future research is needed to evaluate the effect of physician counseling on the weight and physical activity level of their patients BACKGROUND Insufficient evidence exists to support obesity prevention in paediatric primary care . OBJECTIVES To test a theory-based behaviour modification intervention delivered by trained paediatric primary care providers for obesity prevention . METHODS Efficacy trial with cluster r and omization ( practice level ) and a 12-session 12-month sweetened beverages decrease intervention or a comprehensive dietary and physical activity intervention , compared with a control intervention among children ages 8 - 12 years . RESULTS A low recruitment rate was observed . The increase in body mass index z-score ( BMI z ) for the 139 subjects ( 11 practice s ) r and omized to any of the two obesity interventions ( combined group ) was less than that of the 33 subjects ( five practice s ) r and omized to the control intervention ( -0.089 , 95 % confidence interval [ CI ] : -0.170 to -0.008 , P = 0.03 ) with a -1.44 kg weight difference ( 95 % CI : -2.98 to + 0.10 kg , P = 0.095 ) . The incidences of obesity and excess weight gain were lower in the obesity interventions , but the number of subjects was small . Post hoc analyses comparing the beverage only to the control intervention also showed an intervention benefit on BMI z ( -0.083 , 95 % CI : -0.165 to -0.001 , P = 0.048 ) . CONCLUSIONS For participating families , an obesity prevention intervention delivered by paediatric primary care clinicians , who are compensated , trained and continuously supported by behavioural specialists , can impact children 's BMI Aims To compare health effects and risk reduction in two different strategies of nutritional counselling in primary health care for patients at high risk of ischaemic heart disease . Methods In a cluster-r and omized trial 60 general practitioners ( GPs ) in the Copenhagen County were r and omized to give nutritional counselling or to refer patients to a dietician . Patients were included after opportunistically screening ( n = 503 patients ) , and received nutritional counselling by GP or dietician over 12 months . Health effects were measured by changes in weight , waist circumference and blood lipids . Risk of cardiovascular disease was calculated by The Copenhagen Risk Score . Data on use of medicine and primary health care was obtained from central registers . Results Altogether 339 ( 67 % ) patients completed the intervention . Weight loss was larger in the dietician group ( mean 4.5 kg vs. 2.4 kg ) , and increase of HDL-cholesterol was larger in the GP group ( mean 0.13mmol/l vs. 0.03mmol/l ) . The reduction of the cardiovascular risk score was significantly larger in the GP group ( P = 0.0005 ) . Other health outcomes were not significantly different . Conclusions GPs were aware of substantial risk factors of cardiovascular disease and addressed these when counselling . The guidance from a GP was of significant importance for risk reduction in relation to IHD . However , a long-term lifestyle intervention by GP was difficult to implement . In the case of obesity it was effective to refer to long-term nutritional counselling by a dietician BACKGROUND / AIMS Obesity has become a global epidemic , and a major preventable cause of morbidity and mortality . Management strategies and treatment protocol s are however poorly developed and evaluated . The aim of the Counterweight Programme is to develop an evidence -based model for the management of obesity in primary care . METHODS The Counterweight Programme is based on the theoretical model of Evidence -Based Quality Assessment aim ed at improving the management of obese adults ( 18 - 75 years ) in primary care . The model consists of four phases : ( 1 ) practice audit and needs assessment , ( 2 ) practice support and training , ( 3 ) practice nurse-led patient intervention , and ( 4 ) evaluation . Patient intervention consisted of screening and treatment pathways incorporating evidence -based approaches , including patient-centred goal setting , prescribed eating plans , a group programme , physical activity and behavioural approaches , anti-obesity medication and weight maintenance strategies . Weight Management Advisers who are specialist obesity dietitians facilitated programme implementation . Eighty practice s were recruited of which 18 practice s were r and omized to act as controls and receive deferred intervention 2 years after the initial audit . RESULTS By February 2004 , 58 of the 62 ( 93.5 % ) intervention practice s had been trained to run the intervention programme , 47 ( 75.8 % ) practice s were active in implementing the model and 1256 patients had been recruited ( 74 % female , 26 % male , mean age 50.6 years , SD 14 ) . At baseline , 75 % of patients had at one or more co-morbidity , and the mean body mass index ( BMI ) was 36.9 kg/m(2 ) ( SD 5.4 ) . Of the 1256 patients recruited , 91 % received one of the core lifestyle interventions in the first 12 months . For all patients followed up at 12 months , 34 % achieved a clinical meaningful weight loss of 5 % or more . A total of 51 % of patients were classed as compliant in that they attended the required level of appointments in 3 , 6 , and 12 months . For fully compliant patients , weight loss improved with 43 % achieving a weight loss of 5 % or more at 12 months . CONCLUSION The Counterweight Programme is an evidence -based weight management model which is feasible to implement in primary care Objective To determine whether general practice surveillance for childhood obesity , followed by obesity management across primary and tertiary care setting s using a shared care model , improves body mass index and related outcomes in obese children aged 3 - 10 years . Design R and omised controlled trial . Setting 22 family practice s ( 35 participating general practitioners ) and a tertiary weight management service ( three paediatricians , two dietitians ) in Melbourne , Australia . Participants Children aged 3 - 10 years with body mass index above the 95th centile recruited through their general practice between July 2009 and April 2010 . Intervention Children were r and omly allocated to one tertiary appointment followed by up to 11 general practice consultations over one year , supported by shared care , web based software ( intervention ) or “ usual care ” ( control ) . Research ers collecting outcome measurements , but not participants , were blinded to group assignment . Main outcome measures Children ’s body mass index z score ( primary outcome ) , body fat percentage , waist circumference , physical activity , quality of diet , health related quality of life , self esteem , and body dissatisfaction and parents ’ body mass index ( all 15 months post-enrolment ) . Results 118 ( 60 intervention , 56 control ) children were recruited and 107 ( 91 % ) were retained and analysed ( 56 intervention , 51 control ) . All retained intervention children attended the tertiary appointment and their general practitioner for at least one ( mean 3.5 ( SD 2.5 , range 1 - 11 ) ) weight management consultation . At outcome , children in the two trial arms had similar body mass index ( adjusted mean difference −0.1 ( 95 % confidence interval −0.7 to 0.5 ; P=0.7 ) ) and body mass index z score ( −0.05 ( −0.14 to 0.03 ) ; P=0.2 ) . Similarly , no evidence was found of benefit or harm on any secondary outcome . Outcomes varied widely in the combined cohort ( mean change in body mass index z score −0.20 ( SD 0.25 , range −0.97 - 0.47 ) ; 26 % of children resolved from obese to overweight and 2 % to normal weight . Conclusions Although feasible , not harmful , and highly rated by both families and general practitioners , the shared care model of primary and tertiary care management did not lead to better body mass index or other outcomes for the intervention group compared with the control group . Improvements in body mass index in both groups highlight the value of untreated controls when determining efficacy . Trial registration Australian New Zeal and Clinical Trials Registry ACTRN12608000055303 Abstract Background : Practice -based studies are needed to assess how physicians communicate health messages about weight to overweight/obese adolescent patients , but successful recruitment to such studies is challenging . This paper describes challenges , solutions , and lessons learned to recruit physicians and adolescents to the Teen Communicating Health Analyzing Talk ( CHAT ) study , a r and omized controlled trial of a communication skills intervention for primary care physicians to enhance communication about weight with overweight/obese adolescents . Material s and methods : A “ peer-to-peer ” approach was used to recruit physicians , including the use of “ clinic champions ” who liaised between study leaders and physicians . Consistent rapport and cooperative working relationships with physicians and clinic staff were developed and maintained . Adolescent clinic files were review ed ( HIPAA waiver ) to assess eligibility . Parents could elect to opt-out for their children . To encourage enrollment , confidentiality of audio recordings was emphasized , and financial incentives were offered to all participants . Results : We recruited 49 physicians and audio-recorded 391 of their overweight/obese adolescents ’ visits . Recruitment challenges included 1 ) physician reticence to participate ; 2 ) variability in clinic operating procedures ; 3 ) variability in adolescent accrual rates ; 4 ) clinic open access scheduling ; and 5 ) establishing communication with parents and adolescents . Key solutions included the use of a “ clinic champion ” to help recruit physicians , pro-active , consistent communication with clinic staff , and adapting calling times to reach parents and adolescents . Conclusion : Recruiting physicians and adolescents to audio-recorded , practice -based health communication studies can be successful . Anticipated challenges to recruiting can be met with advanced planning ; however , optimal solutions to challenges evolve as recruitment progresses |
1,275 | 18,646,178 | Gliadel(R ) results in a prolongation of survival without an increased incidence of adverse events when used as primary therapy .
There is no evidence of enhanced progression free survival ( PFS ) or QOL .
In recurrent disease , Gliadel(R ) does not appear to confer any added benefit . | BACKGROUND St and ard treatment for high grade glioma ( HGG ) usually entails biopsy or surgical resection where possible followed by radiotherapy .
Systemic chemotherapy is usually only given in selected cases and its use is often limited by side effects .
Implanting wafers impregnated with chemotherapy agents into the resection cavity represents a novel means of delivering drugs to the central nervous system ( CNS ) with fewer side effects .
It is not clear how effective this modality is or whether it should be recommended as part of st and ard care for HGG .
OBJECTIVES To assess whether chemotherapeutic wafers have any advantage over conventional therapy for HGG . | High- quality cancer registry data are essential for assessing trends in incidence rates . This study evaluated the consistency of brain tumor surveillance data using a r and om sample of cases from the Connecticut Tumor Registry . Three neuropathologists independently and blindly review ed tumor slides from 204 cases and a nosologist blindly review ed and assigned International Classification of Diseases for Oncology ( ICD-O ) codes to 326 cases . For the pathology review , absolute concordance was as high as 81 % for all primary brain tumors . Absolute concordance rates were high for nerve sheath ( 89 % ) , meningioma ( 95 % ) , and pituitary ( 95 % ) tumors . Rates were much lower for malignant tumors . ICD-O coding of malignant brain tumors is of relatively high quality with the exception of mixed gliomas and unspecified tumors . A high level of consistency for nonmalignant brain tumor diagnoses suggests that rates for these tumors , when actively reported to a surveillance system , can be of high quality A controlled , prospect i ve , r and omized study evaluated the use of 1,3-bis(2-chloroethyl)-1-nitrosourea ( BCNU ) and /or radiotherapy in the treatment of patients who were operated on and had histological confirmation of anaplastic glioma . A total of 303 patients were r and omized into this study , of whom 222 ( 73 % ) were within the Valid Study Group ( VSG ) , having met the protocol criteria of neuropathology , corticosteroid control , and therapeutic approach . Patients were divided into four r and om groups , and received BCNU ( 80 mg/sq m/day on 3 successive days every 6 to 8 weeks ) , and /or radiotherapy ( 5000 to 6000 rads to the whole brain through bilateral opposing ports ) , or best conventional care but no chemotherapy or radiotherapy . Analysis was performed on all patients who received any amount of therapy ( VSG ) and on the Adequately Treated Group ( ATG ) , who had received 5000 or more rads radiotherapy , two or more courses of chemotherapy , and had a minimum survival of 8 or more weeks ( the interval that would have been required to have received either the radiotherapy or chemotherapy ) . Median survival of patients in the VSG was , best conventional care : 14 weeks ( ATG : 17.0 weeks ) ; BCNU : 18.5 weeks ( ATG : 25.0 weeks ) ; radiotherapy : 35 weeks ( ATG : 37.5 weeks ) ; and BCNU plus radiotherapy : 34.5 weeks ( ATG : 40.5 weeks ) . All therapeutic modalities showed some statistical superiority compared to best conventional care . There was no significant difference between the four groups in relation to age distribution , sex , location of tumor , diagnosis , tumor characteristics , signs or symptoms , or the amount of corticosteroid used . An analysis of prognostic factors indicates that the initial performance status ( Karnofsky rating ) , age , the use of only a surgical biopsy , parietal location , the presence of seizures , or the involvement of cranial nerves II , III , IV , and VI are all of significance . Toxicity included acceptable , reversible thrombocytopenia and leukopenia Abstract Objective : Recently a r and omized placebo-controlled phase III trial of biodegradable polymers containing carmustine has demonstrated a significant survival benefit for patients treated with local chemotherapy . A local chemotherapy applied directly to the resection cavity may act directly on residual tumor cells in adjacent brain possibly leading to a local control of the tumor and increased survival . Methods : We have analyzed the pattern of recurrence using serial MRI studies of 24 patients treated with GLIADEL ® Wafers or placebo wafers following resection of glioblastomas . Results : Of 24 patients 11 received carmustine wafers and 13 placebo . The age distribution and Karnowsky performance scores of the two population s were not different . However , the median survival ( 14.7 versus 9.5 months ; P = 0.007 ) and the time to neurological deterioration ( 12.9 ± 4.85 vs. 9.4 ± 2.73 months ; P = 0.035 ) was significantly longer in the treatment group versus the placebo treated control . Preoperative and follow up MRI studies were evaluated in a blinded fashion . Out of 24 patients that entered the analysis 11 showed clearance of all contrast enhancement following resection of glioblastomas . Seventeen tumors progressed locally and 7 showed different patterns of distant failure . Within the carmustine treated group 8 patients showed a local treatment failure with recurrent tumors immediately adjacent to the resection cavity or progression form a residual tumor . Three patients showed a multifocal distant and local pattern of failure after complete or subtotal removal . In no case the local chemotherapy result ed in a distant recurrence only . However , the time to radiographic progression was 165.1 ± 80.75 days for the GLIADEL ® Wafer group and 101.9 ± 43.06 days for the placebo group ( P = 0.023 ) . Conclusion : In this subgroup analysis of a phase III trial population both the clinical progression and radiological progression were significantly delayed in patients treated with local chemotherapy , result ing in an increased survival time . Local chemotherapy with carmustine containing wafer implants did not result in an altered pattern of recurrence and did not promote multifocal patterns of recurrence A previous placebo-controlled trial has shown that biodegradable 1,3-bis (2-chloroethyl)-1-nitrosourea ( BCNU ) wafers ( Gliadel wafers ) prolong survival in patients with recurrent glioblastoma multiforme . A previously completed phase 3 trial , also placebo controlled , in 32 patients with newly diagnosed malignant glioma also demonstrated a survival benefit in those patients treated with BCNU wafers . Because of the small number of patients in that trial , a larger phase 3 trial was performed to confirm these results . Two hundred forty patients were r and omized to receive either BCNU or placebo wafers at the time of primary surgical resection ; both groups were treated with external beam radiation postoperatively . The two groups were similar for age , sex , Karnofsky performance status ( KPS ) , and tumor histology . Median survival in the intent-to-treat group was 13.9 months for the BCNU wafer-treated group and 11.6 months for the placebo-treated group ( log-rank P -value stratified by country = 0.03 ) , with a 29 % reduction in the risk of death in the treatment group . When adjusted for factors affecting survival , the treatment effect remained positive with a risk reduction of 28 % ( P = 0.03 ) . Time to decline in KPS and in 10/11 neuroperformance measures was statistically significantly prolonged in the BCNU wafer-treated group ( P < /= 0.05 ) . Adverse events were comparable for the 2 groups , except for CSF leak ( 5 % in the BCNU wafer-treated group vs. 0.8 % in the placebo-treated group ) and intracranial hypertension ( 9.1 % in the BCNU wafer-treated group vs. 1.7 % in the placebo group ) . This study confirms that local chemotherapy with BCNU wafers is well tolerated and offers a survival benefit to patients with newly diagnosed malignant glioma The results of a multi-institutional phase I trial evaluating the safety of surgically implanted biodegradable 1,3-bis(chloro-ethyl)-1-nitrosourea ( BCNU ) impregnated polymer as theinitial therapy for malignant brain tumors are reported . This is the first study of locally delivered BCNU and st and ard external beam radiation therapy ( XRT ) given concurrently . Twenty-two patients were treated at three hospitals . The entry criteria were : single unilateral tumor focus larger than 1 cm3 ; age over 18 years ; Karnofsky Performance Score ( KPS ) of at least 60 h ; and an intra-operative diagnosis of malignant glioma . Twenty-one of twenty-two patients had glioblastoma multiforme . After surgery , seven or eight BCNU-loaded polyanhydride polymer discs ( 7.7 mg BCNU each ) were placed in the resection cavity . Postoperatively , all patients received st and ard radiation therapy ; none received additional chemotherapy in the first 6 months . Neurotoxicity , systemic toxicity , and survival were assessed . No perioperative mortality was seen . Neurotoxicity was equivalent to that occurring in other series of patients undergoing craniotomy and XRT without local chemotherapy . Systematic ally , no significant bone marrow suppression occurred , and there were no wound infections . Median survival in this group of older patients ( mean age=60 ) was 42 weeks , 8 patients survived 1 year , and 4 patients survived more than 18 months . Interstitial chemotherapy with BCNU-polymer with subsequent radiation therapy appears to be safe as an initial therapy . Several long-term survivors in this group of older patients with predominantly glioblastoma suggests efficacy in some patients . Dose escalation and efficacy trials are planned to further evaluate interstitial chemotherapy for the initial treatment of malignant gliomas This clinical study was design ed to evaluate the safety and efficacy of the sustained release form of dibutryl adenosine-3′,5′-cyclic monophosphate ( dB-cAMP , bucladesine ) placed in the tumor resection cavity at the time of recurrence of the de novo glioblastoma multiforme ( GBM ) patients .In a r and omized prospect i ve manner , 40 patients who were diagnosed as GBM in their first operations were included in this study . Four different therapy protocol s were used : First group of 10 patients had tumor resection only . Second group assessed had only systemic chemotherapy as six i.v . infusions of fotémustine after tumor resection . Third group had implantation of bucladesine-loaded biodegradable polymeric sustained release ( bcl-SR ) pellets while the last group received six i.v . infusions of systemic fotémustine as in the second group in addition to local implantation of bcl-SR pellets . A biodegradable polymer , poly-dl-lactide-co-glycolide with molecular weight of 80 000 , was used as carrier matrix for the drug with an approximately 4–5 months of release time . Maximal doses of 20 mg of bucladesine with a mean dose of 15.5 mg were implanted . No bone marrow suppression occurred and there were no wound infections as far as the local bucladesine-loaded polymer therapy is concerned . In this r and omized prospect i ve trial of local interstitial chemotherapy with long acting bcl-SR did show a statistically significant delay of recurrence on the treatment of GBM patients . Best treatment results obtained from the local bcl-SR + systemic fotémustine treated group in which survival rate estimated by the Kaplan – Meier method was 70 % in de novo GBM at 12 months OBJECTIVE To find out the effect of carmustine ( bischloroethyl-nitrosourea ) combined with a biodegradable polymer in the treatment of malignant ( Grade s III and IV ) gliomas , applied locally , at the time of the primary operation . METHODS Prospect i ve , r and omized double-blind study of an active treatment group versus a placebo group . Conducted at the Departments of Neurosurgery of the University Hospitals of Helsinki , Tampere , and Turku in Finl and and Trondheim in Norway . The study consisted of 32 patients ( 16 in each treatment group ) enrolled between March 23 , 1992 , and March 19 , 1993 . The study was planned to include 100 patients but had to be terminated prematurely , because the drug that was being used had become unobtainable . The main outcome measures included the survival times of patients after the operations and the application of an active drug or placebo . RESULTS The median time from surgery to death was 58.1 weeks for the active treatment group versus 39.9 weeks for the placebo group ( P = 0.012 ) . For 27 patients with Grade IV tumors , the corresponding times were 39.9 weeks for the placebo group and 53.3 weeks for the active treatment group ( P = 0.008 ) . At the end of the study , six patients were still alive , five of whom belonged to the active treatment group . CONCLUSION Carmustine applied locally in a biodegradable polymer at the time of primary operation , seems to have a favorable effect on the life span of patients with high- grade gliomas Abstract Glioblastoma multiforme ( GBM ) makes up as many as 30 % of all primary brain tumors . Despite the employment of multimodal antitumor treatment , the overall survival is less than one year . Between 06/01/1998 and 06/01/2000 17 patients ( Group A ) with GBM ( 11 males , 6 females ; median age 54.3 years ) were administered local chemotherapy with cisplatin incorporated into biodegradable 6-carboxylcellulose polymer ( cisplatin-depot ( CDDP-D ) ) . After the subtotal removal of GBM , twenty 1.5 × 1.5 cm polymer plates with a total area of 45 cm2 ( the density of cisplatin immobilization on 6-carboxylcellulose being 1 mg/cm2 , a total cisplatin dose of 45 mg ) were implanted into the tumor bed . Group B ( 21 patients with GBM ; 11 males , 10 females ; median age 53.2 years ) was control : the subtotal tumor ablation without CDDP-D implantation . Two to three weeks after the surgery all the patients of Groups A and B started a course of radiation therapy . A total dose of cranial irradiation was 20 Gy ( 1 fraction/day , 5 days/week ; a daily dose of 2 Gy ) followed by a boost tumor bed irradiation ( 1 fraction/day , 5 days/week ; a daily dose of 2 Gy ) up to the conventional dose of 60 Gy . Survival data for the patients were processed using the Kaplan – Meier method and analyzed by logrank test . All the patients of Group A tolerated surgical ablation of the brain tumor without side effects ( brain edema , seizures , etc . ) . No patient of Group A had a reduction in blood cell counts during six weeks that would indicate systemic exposure to cisplatin . Blood chemistry and urinalysis did not show evidence of renal injury . No side effects of radiotherapy were registered in Group B either , regarding both the psychoneurological status of the patients and the basic values of homeostasis . Karnofsky performance scale ( KPS ) score of Group A and Group B patients demonstrated no significant differences before and after the surgery . The median overall survivals for patients of Group A and Group B were 427.5 and 211.0 days respectively ( p=0.00001 ; overall logrank test ) . Conclusion . Local chemotherapy of GBM with CDDP-D followed by irradiation is well tolerated and effective BACKGROUND Glioblastoma , the most common primary brain tumor in adults , is usually rapidly fatal . The current st and ard of care for newly diagnosed glioblastoma is surgical resection to the extent feasible , followed by adjuvant radiotherapy . In this trial we compared radiotherapy alone with radiotherapy plus temozolomide , given concomitantly with and after radiotherapy , in terms of efficacy and safety . METHODS Patients with newly diagnosed , histologically confirmed glioblastoma were r and omly assigned to receive radiotherapy alone ( fractionated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 weeks , for a total of 60 Gy ) or radiotherapy plus continuous daily temozolomide ( 75 mg per square meter of body-surface area per day , 7 days per week from the first to the last day of radiotherapy ) , followed by six cycles of adjuvant temozolomide ( 150 to 200 mg per square meter for 5 days during each 28-day cycle ) . The primary end point was overall survival . RESULTS A total of 573 patients from 85 centers underwent r and omization . The median age was 56 years , and 84 percent of patients had undergone debulking surgery . At a median follow-up of 28 months , the median survival was 14.6 months with radiotherapy plus temozolomide and 12.1 months with radiotherapy alone . The unadjusted hazard ratio for death in the radiotherapy-plus-temozolomide group was 0.63 ( 95 percent confidence interval , 0.52 to 0.75 ; P<0.001 by the log-rank test ) . The two-year survival rate was 26.5 percent with radiotherapy plus temozolomide and 10.4 percent with radiotherapy alone . Concomitant treatment with radiotherapy plus temozolomide result ed in grade 3 or 4 hematologic toxic effects in 7 percent of patients . CONCLUSIONS The addition of temozolomide to radiotherapy for newly diagnosed glioblastoma result ed in a clinical ly meaningful and statistically significant survival benefit with minimal additional toxicity |
1,276 | 23,983,134 | CONCLUSION Low-dose RTX has similar effectiveness and met noninferiority criteria for most primary outcomes . | OBJECTIVE The approved dose of rituximab ( RTX ) for rheumatoid arthritis ( RA ) is 2 × 1,000 mg infusions given 2 weeks apart .
There is contradictory evidence regarding the effectiveness of a lower-dose regimen ( 2 × 500 mg ) of RTX .
Our aim was to compare the efficacy and safety of low- and high-dose RTX and to test the noninferiority of the low-dose regimen . | Objectives Rituximab is an effective treatment in patients with established rheumatoid arthritis ( RA ) . The objective of the IMAGE study was to determine the efficacy of rituximab in the prevention of joint damage and its safety in combination with methotrexate ( MTX ) in patients initiating treatment with MTX . Methods In this double-blind r and omised controlled phase III study , 755 MTX-naïve patients with active RA were r and omly assigned to MTX alone , rituximab 2 × 500 mg + MTX or rituximab 2 × 1000 mg + MTX . The primary end point at week 52 was the change in joint damage measured using a Genant-modified Sharp score . Results 249 , 249 and 250 patients were r and omly assigned to MTX alone , rituximab 2 × 500 mg + MTX or rituximab 2 × 1000 mg + MTX , respectively . At week 52 , treatment with rituximab 2 × 1000 mg + MTX compared with MTX alone was associated with a reduction in progression of joint damage ( mean change in total modified Sharp score 0.359 vs 1.079 ; p=0.0004 ) and an improvement in clinical outcomes ( ACR50 65 % vs 42 % ; p<0.0001 ) ; rituximab 2 × 500 mg + MTX improved clinical outcomes ( ACR50 59 % vs 42 % ; p<0.0001 ) compared with MTX alone but did not significantly reduce the progression of joint damage . Safety outcomes were similar between treatment groups . Conclusions Treatment with rituximab 2 × 1000 mg in combination with MTX is an effective therapy for the treatment of patients with MTX-naïve RA . CLinical Trials.gov identifier NCT00299104 Objectives This phase III study evaluated the efficacy and safety of rituximab plus methotrexate ( MTX ) in patients with active rheumatoid arthritis ( RA ) who had an inadequate response to MTX and who were naïve to prior biological treatment . Methods Patients with active disease on stable MTX ( 10–25 mg/week ) were r and omised to rituximab 2 × 500 mg ( n=168 ) , rituximab 2 × 1000 mg ( n=172 ) , or placebo ( n=172 ) . From week 24 , patients not in remission ( Disease Activity Score ( 28 joints ) ≥2.6 ) received a second course of rituximab ; patients initially assigned to placebo switched to rituximab 2 × 500 mg . The primary end point was American College of Rheumatology 20 ( ACR20 ) response at week 24 . All patients were followed until week 48 . Results At week 24 , both doses of rituximab showed statistically superior efficacy ( p<0.0001 ) to placebo ( ACR20 : 54 % , 51 % and 23 % ; rituximab ( 2 × 500 mg ) + MTX , rituximab ( 2 × 1000 mg ) + MTX and placebo + MTX , respectively ) . Secondary end points were also significantly improved for both rituximab groups compared with placebo . Further improvements in both rituximab arms were observed from week 24 to week 48 . Rituximab + MTX was well tolerated , demonstrating comparable safety to placebo + MTX through to week 24 , and between rituximab doses through to week 48 . Conclusions Rituximab ( at 2 × 500 mg and 2 × 1000 mg ) plus MTX significantly improved clinical outcomes at week 24 , which were further improved by week 48 . No significant differences in either clinical or safety outcomes were apparent between the rituximab doses BACKGROUND An open-label study indicated that selective depletion of B cells with the use of rituximab led to sustained clinical improvements for patients with rheumatoid arthritis . To confirm these observations , we conducted a r and omized , double-blind , controlled study . METHODS We r and omly assigned 161 patients who had active rheumatoid arthritis despite treatment with methotrexate to receive one of four treatments : oral methotrexate ( > or = 10 mg per week ) ( control ) ; rituximab ( 1000 mg on days 1 and 15 ) ; rituximab plus cyclophosphamide ( 750 mg on days 3 and 17 ) ; or rituximab plus methotrexate . Responses defined according to the criteria of the American College of Rheumatology ( ACR ) and the European League against Rheumatism ( EULAR ) were assessed at week 24 ( primary analyses ) and week 48 ( exploratory analyses ) . RESULTS At week 24 , the proportion of patients with 50 percent improvement in disease symptoms according to the ACR criteria , the primary end point , was significantly greater with the rituximab-methotrexate combination ( 43 percent , P=0.005 ) and the rituximab-cyclophosphamide combination ( 41 percent , P=0.005 ) than with methotrexate alone ( 13 percent ) . In all groups treated with rituximab , a significantly higher proportion of patients had a 20 percent improvement in disease symptoms according to the ACR criteria ( 65 to 76 percent vs. 38 percent , P < or = 0.025 ) or had EULAR responses ( 83 to 85 percent vs. 50 percent , P < or = 0.004 ) . All ACR responses were maintained at week 48 in the rituximab-methotrexate group . The majority of adverse events occurred with the first rituximab infusion : at 24 weeks , serious infections occurred in one patient ( 2.5 percent ) in the control group and in four patients ( 3.3 percent ) in the rituximab groups . Peripheral-blood immunoglobulin concentrations remained within normal ranges . CONCLUSIONS In patients with active rheumatoid arthritis despite methotrexate treatment , a single course of two infusions of rituximab , alone or in combination with either cyclophosphamide or continued methotrexate , provided significant improvement in disease symptoms at both weeks 24 and 48 R and omized controlled trials often suffer from two major complications , i.e. , noncompliance and missing outcomes . One potential solution to this problem is a statistical concept called intention-to-treat ( ITT ) analysis . ITT analysis includes every subject who is r and omized according to r and omized treatment assignment . It ignores noncompliance , protocol deviations , withdrawal , and anything that happens after r and omization . ITT analysis maintains prognostic balance generated from the original r and om treatment allocation . In ITT analysis , estimate of treatment effect is generally conservative . A better application of the ITT approach is possible if complete outcome data are available for all r and omized subjects . Per- protocol population is defined as a subset of the ITT population who completed the study without any major protocol violations Background In the IMAGE study , rituximab plus methotrexate ( MTX ) inhibited joint damage and improved clinical outcomes at 1 year in MTX-naïve patients with early active rheumatoid arthritis . Objective The aim of this study was to assess joint damage progression and clinical outcomes over 2 years . Methods Patients ( n=755 ) were r and omised to receive rituximab 2 × 500 mg+MTX , 2 × 1000 mg+MTX or placebo+MTX . The placebo-controlled period continued to week 104 . Two-year end points were defined as secondary or exploratory and included change in total Genant-modified Sharp score ( mTSS ) , total erosion score and joint space narrowing score from baseline to week 104 . Clinical efficacy and physical function end points were also assessed . Results At 2 years , rituximab 2 × 1000 mg+MTX maintained inhibition of progressive joint damage versus MTX alone ( mTSS change 0.41 vs 1.95 ; p<0.0001 ( 79 % inhibition ) ) , and a higher proportion of patients receiving rituximab 2 × 1000 mg+MTX had no radiographic progression over 2 years compared with those receiving MTX alone ( 57 % vs 37 % ; p<0.0001 ) . Contrary to 1-year results , exploratory analysis of rituximab 2 × 500 mg+MTX at 2 years showed that progressive joint damage was slowed by ∼61 % versus placebo+MTX ( mTSS , exploratory p=0.0041 ) . Improvements in clinical signs and symptoms and physical function seen after 1 year in rituximab-treated patients versus those receiving placebo were maintained at year 2 . Safety profiles were similar between groups . Conclusions Treatment with rituximab 2 × 1000 mg+MTX was associated with sustained improvements in radiographic , clinical and functional outcomes over 2 years . Clinical trials.gov identifier NCT00299104 Objective . To evaluate the efficacy and safety of three dosing and repeat treatment regimens of rituximab ( RTX ) plus MTX in patients with active RA . Methods . Patients with active RA despite stable MTX ( 10–25 mg/week ) were r and omly assigned to one of the three treatment regimens comprising two courses of RTX given 24 weeks apart : 2 × 500 and 2 × 500 mg ; 2 × 500 and 2 × 1000 mg ( dose escalation ) ; and 2 × 1000 and 2 × 1000 mg . The primary endpoint was proportion of patients achieving ACR20 at Week 48 . Results . At Week 48 , ACR20 responses were not statistically significantly different between the dose regimens . Compared with RTX 2 × 500 mg ( n = 134 ) or dose escalation ( n = 119 ) , ACR and European League Against Rheumatism ( EULAR ) outcomes in the RTX 2 × 1000 mg group ( n = 93 ) were consistently higher , with significantly more patients achieving EULAR responses ( P = 0.0495 ) . At Week 48 , rituximab 2 × 1000 mg was associated with a higher proportion of patients who , following retreatment , maintained or improved their Week 24 responses . Dose escalation from 2 × 500 to 2 × 1000 mg did not appear to be associated with improved outcomes compared with continual 2 × 500 mg . All RTX regimens demonstrated comparable safety . Conclusions . RTX 2 × 500 and 2 × 1000 mg could not be clearly differentiated , although some efficacy outcomes suggest improved outcomes in the rituximab 2 × 1000 mg group . Retreatment from Week 24 result ed in a sustained suppression of disease activity through to Week 48 . Trial registration . Clinical Trials.gov , http:// clinical trials.gov/ , NCT00422383 OBJECTIVE To define clinical ly meaningful changes in 2 widely used health-related quality of life ( HQL ) instruments in studies of patients with rheumatoid arthritis ( RA ) . METHODS Patients with RA ( n = 693 ) who were enrolled in 2 double-blind , placebo-controlled clinical trials completed the Short Form 36 ( SF-36 ) modified health survey and the Health Assessment Question naire ( HAQ ) disability index at baseline and 6-week followup assessment s. Data on 5 RA severity measures were also collected at baseline and at 6 weeks ( patient and physician global assessment s , joint swelling and tenderness counts , and global pain assessment ) . Comparison of changes in the SF-36 scales and HAQ scores was made between groups of patients known to differ in the level of change on each RA severity measure . RESULTS With few exceptions , changes in the SF-36 and HAQ scores were different between patients who differed in the level of change on each RA severity measure . Changes in the SF-36 and HAQ scores were more strongly related to changes in the patient and physician global assessment s and patient pain assessment than to changes in the joint swelling and tenderness counts . CONCLUSION Based on these results , minimally important changes in the SF-36 scales and HAQ disability scores were determined , which will be useful in interpreting HQL results in clinical trials OBJECTIVE To examine the efficacy and safety of different rituximab doses plus methotrexate ( MTX ) , with or without glucocorticoids , in patients with active rheumatoid arthritis ( RA ) resistant to disease-modifying antirheumatic drugs ( DMARDs ) , including biologic agents . METHODS A total of 465 patients were r and omized into 9 treatment groups : 3 rituximab groups ( placebo [ n = 149 ] , 500 mg [ n = 124 ] , or 1,000 mg [ n = 192 ] on days 1 and 15 ) each also taking either placebo glucocorticoids , intravenous methylprednisolone premedication , or intravenous methylprednisolone premedication plus oral prednisone for 2 weeks . All patients received MTX ( 10 - 25 mg/week ) ; no other DMARDs were permitted . RESULTS Significantly more patients who received 2 500-mg or 2 1,000-mg infusions of rituximab met the American College of Rheumatology 20 % improvement criteria ( achieved an ACR20 response ) at week 24 ( 55 % and 54 % , respectively ) compared with placebo ( 28 % ; P < 0.0001 ) . ACR50 responses were achieved by 33 % , 34 % , and 13 % of patients , respectively ( P < 0.001 ) , and ACR70 responses were achieved by 13 % , 20 % , and 5 % of patients ( P < 0.05 ) . Changes in the Disease Activity Score in 28 joints ( -1.79 , -2.05 , -0.67 ; P < 0.0001 ) and moderate to good responses on the European League Against Rheumatism criteria ( P < 0.0001 ) reflected the ACR criteria responses . Glucocorticoids did not contribute significantly to the primary efficacy end point , ACR20 response at 24 weeks . Intravenous glucocorticoid premedication reduced the frequency and intensity of first infusion-associated events ; oral glucocorticoids conferred no additional safety benefit . Rituximab was well tolerated ; the type and severity of infections was similar to those for placebo . CONCLUSION Both rituximab doses were effective and well tolerated when added to MTX therapy in patients with active RA . The primary end point ( ACR20 response ) was independent of glucocorticoids , although intravenous glucocorticoid premedication improved tolerability during the first rituximab infusion OBJECTIVE To determine the efficacy and safety of treatment with rituximab plus methotrexate ( MTX ) in patients with active rheumatoid arthritis ( RA ) who had an inadequate response to anti-tumor necrosis factor ( anti-TNF ) therapies and to explore the pharmacokinetics and pharmacodynamics of rituximab in this population . METHODS We evaluated primary efficacy and safety at 24 weeks in patients enrolled in the R and omized Evaluation of Long-Term Efficacy of Rituximab in RA ( REFLEX ) Trial , a 2-year , multicenter , r and omized , double-blind , placebo-controlled , phase III study of rituximab therapy . Patients with active RA and an inadequate response to 1 or more anti-TNF agents were r and omized to receive intravenous rituximab ( 1 course , consisting of 2 infusions of 1,000 mg each ) or placebo , both with background MTX . The primary efficacy end point was a response on the American College of Rheumatology 20 % improvement criteria ( ACR20 ) at 24 weeks . Secondary end points were responses on the ACR50 and ACR70 improvement criteria , the Disease Activity Score in 28 joints , and the European League against Rheumatism ( EULAR ) response criteria at 24 weeks . Additional end points included scores on the Functional Assessment of Chronic Illness Therapy-Fatigue ( FACIT-F ) , Health Assessment Question naire ( HAQ ) Disability Index ( DI ) , and Short Form 36 ( SF-36 ) instruments , as well as Genant-modified Sharp radiographic scores at 24 weeks . RESULTS Patients assigned to placebo ( n = 209 ) and rituximab ( n = 311 ) had active , longst and ing RA . At week 24 , significantly more ( P < 0.0001 ) rituximab-treated patients than placebo-treated patients demonstrated ACR20 ( 51 % versus 18 % ) , ACR50 ( 27 % versus 5 % ) , and ACR70 ( 12 % versus 1 % ) responses and moderate-to-good EULAR responses ( 65 % versus 22 % ) . All ACR response parameters were significantly improved in rituximab-treated patients , who also had clinical ly meaningful improvements in fatigue , disability , and health-related quality of life ( demonstrated by FACIT-F , HAQ DI , and SF-36 scores , respectively ) and showed a trend toward less progression in radiographic end points . Rituximab depleted peripheral CD20 + B cells , but the mean immunoglobulin levels ( IgG , IgM , and IgA ) remained within normal ranges . Most adverse events occurred with the first rituximab infusion and were of mild-to-moderate severity . The rate of serious infections was 5.2 per 100 patient-years in the rituximab group and 3.7 per 100 patient-years in the placebo group . CONCLUSION At 24 weeks , a single course of rituximab with concomitant MTX therapy provided significant and clinical ly meaningful improvements in disease activity in patients with active , longst and ing RA who had an inadequate response to 1 or more anti-TNF therapies OBJECTIVE To evaluate the effect of rituximab treatment on health-related quality of life ( HRQOL ) in patients with active rheumatoid arthritis ( RA ) , who have had an inadequate response to disease-modifying antirheumatic drugs , including biologic agents . METHODS A r and omized , multicenter , double-blind , placebo-controlled clinical trial involving 367 rheumatoid factor-positive patients was conducted . Patients received 2 infusions 2 weeks apart of placebo ( n = 122 ) , rituximab 500 mg ( n = 123 ) , or rituximab 1000 mg ( n = 122 ) , with or without glucocorticoids . All patients received stable doses of methotrexate ( 10 25 mg/wk ) . Measures included SF-36 , assessed at baseline and at 24 weeks , as well as the HAQ and FACIT-Fatigue scale assessed at baseline and monthly for 24 weeks . Patients exceeding prespecified minimal clinical ly important differences ( MCID ) were examined . Clinical efficacy measurements ( ACR20/50/70 and EULAR responses ) were compared with HRQOL outcomes . RESULTS At 24 weeks , the rituximab 500 mg and 1000 mg groups both reported statistically significantly greater improvements on the SF-36 physical component summary ( 4.37 and 4.89 points higher , respectively , vs placebo ; p < 0.001 ) . SF-36 physical function , bodily pain , vitality , social function , and role-physical subscale scores also statistically significantly improved vs placebo . At 24 weeks , 62.6 % and 67.2 % of the rituximab 500 mg and 1000 mg groups , respectively , exceeded the MCID of 0.22 in HAQ ( p < 0.001 ) . For FACIT-Fatigue , 55.3 % and 65.6 % of patients exceeded the MCID of 3.5 points compared with 35.2 % of placebo over 24 weeks ( p < 0.001 ) . ACR20/50/70 and EULAR responders demonstrated greater improvements in mean baseline to 24 week changes in SF-36 and FACIT-Fatigue scores compared with nonresponders ( p < 0.05 ) . CONCLUSION Both rituximab doses in combination with methotrexate were effective in improving all HRQOL outcomes in patients with active RA consistent with clinical efficacy To assess the effect of rituximab plus methotrexate ( MTX ) compared with MTX alone on patient‐reported outcomes ( PROs ) and health‐related quality of life ( HRQOL ) in patients with active early rheumatoid arthritis ( RA ) previously untreated with MTX OBJECTIVES This study assessed the utility of rituximab for the therapy of RA in a non-academic environment in a group of cases where anti-TNF was either not available or relatively contraindicated . METHODS Thirty-nine patients with active RA who had failed at least one DMARD received two rituximab infusions 2 weeks apart . Seventeen patients received two 1000 mg doses , and 22 received the 500 mg regimen . The 28-joint disease activity index ( DAS28 ) and European League against Rheumatism ( EULAR ) response criteria were recorded at baseline , 3 , 6 , 9 and 12 months . RF and ANA were recorded at baseline and at 6 and 12 months . RESULTS There was a significant improvement in the DAS28 at all time points , and EULAR response was observed in 29 of 33 patients ( 87.9 % ) at 3 months , 25 of 33 patients ( 75.8 % ) at 6 months , 22 of 29 patients ( 75.9 % ) at 9 months and 23 of 30 patients ( 76.7 ) at 12 months . Improvement was also noted in CRP , and both RF and ANA were generally reduced after treatment . Patients who were on the higher regimen of two 1000 mg doses appeared to respond slightly better compared with the lower dose regimen . CONCLUSIONS Rituximab is well tolerated in everyday clinical practice and may represent a good short-term treatment option where anti-TNF therapy is either unavailable or relatively contraindicated |
1,277 | 31,924,636 | There was no effect on progression to ESRF .
Somatostatin analogues were associated with known adverse effects such as gastrointestinal symptoms .
Conclusions The available RCT data show improvement in TLV with somatostatin analogue treatment .
There was no benefit to TKV or eGFR in patients with ADPKD , while being associated with various side effects . | Objectives A number of r and omised control trials ( RCTs ) investigating the effects of long-acting somatostatin analogues in autosomal dominant polycystic kidney disease ( ADPKD ) and polycystic liver disease ( PLD ) have been recently reported .
We sought to evaluate all available RCTs investigating the efficacy of somatostatin analogues treatment in ADPKD and PLD . | Background Symptoms in polycystic liver disease ( PLD ) are thought to be caused by compression of organs and structures by the enlarged liver . Aim The aim of this article is to assess the impact of liver volume on symptoms and quality of life ( QoL ) in PLD . Methods We included PLD patients from two prospect i ve studies that used the PLD- question naire ( PLD-Q ) for symptom assessment . QoL was assessed through SF-36 , summarized in a physical ( PCS ) and mental ( MCS ) component score . Liver volume was correlated with PLD-Q total scores . Patients were classified based on height-corrected liver volume in mild ( < 1600 ml ) , moderate ( 1600–3200 ml ) , and severe ( > 3200 ml ) disease . PLD-Q and QoL ( PCS and MCS ) scores were compared across disease stages . Results We included 82 of 131 patients from the original studies ( disease stages ; mild n = 26 , moderate n = 33 , and severe n = 23 ) . Patients with larger liver volume reported higher symptom burden ( r = 0.516 , p < 0.001 ) . Symptom scores increased with disease progression , except for abdominal pain ( p = 0.088 ) . PCS decreased with advancing disease ( p < 0.001 ) , in contrast to MCS ( p = 0.055 ) . Moderate ( p = 0.007 ) and severe ( p < 0.001 ) PLD patients had lower PCS scores than the general population . Conclusion PLD with larger liver volume is more likely to be symptomatic and is associated with lower BACKGROUND & AIMS Therapy for polycystic liver is invasive , expensive , and has disappointing long-term results . Treatment with somatostatin analogues slowed kidney growth in patients with polycystic kidney disease ( PKD ) and reduced liver and kidney volume in a PKD rodent model . We evaluated the effects of lanreotide , a somatostatin analogue , in patients with polycystic liver because of autosomal-dominant ( AD ) PKD or autosomal-dominant polycystic liver disease ( PCLD ) . METHODS We performed a r and omized , double-blind , placebo-controlled trial in 2 tertiary referral centers . Patients with polycystic liver ( n = 54 ) were r and omly assigned to groups given lanreotide ( 120 mg ) or placebo , administered every 28 days for 24 weeks . The primary end point was the difference in total liver volume , measured by computerized tomography at weeks 0 and 24 . Analyses were performed on an intention-to-treat basis . RESULTS Baseline characteristics were comparable for both groups , except that more patients with ADPKD were assigned to the placebo group ( P = .03 ) . The mean liver volume decreased 2.9 % , from 4606 mL ( 95 % confidence interval ( CI ) : 547 - 8665 ) to 4471 mL ( 95 % CI : 542 - 8401 mL ) , in patients given lanreotide . In the placebo group , the mean liver volume increased 1.6 % , from 4689 mL ( 95 % CI : 613 - 8765 mL ) to 4895 mL ( 95 % CI : 739 - 9053 mL ) ( P < .01 ) . Post hoc stratification for patients with ADPKD or PCLD revealed similar changes in liver volume , with statistically significant differences in patients given lanreotide ( P < .01 for both diseases ) . CONCLUSIONS In patients with polycystic liver , 6 months of treatment with lanreotide reduces liver volume There are no proven , effective therapies for polycystic kidney disease ( PKD ) or polycystic liver disease ( PLD ) . We enrolled 42 patients with severe PLD result ing from autosomal dominant PKD ( ADPKD ) or autosomal dominant PLD ( ADPLD ) in a r and omized , double-blind , placebo-controlled trial of octreotide , a long-acting somatostatin analogue . We r and omly assigned 42 patients in a 2:1 ratio to octreotide LAR depot ( up to 40 mg every 28+/-5 days ) or placebo for 1 year . The primary end point was percent change in liver volume from baseline to 1 year , measured by MRI . Secondary end points were changes in total kidney volume , GFR , quality of life , safety , vital signs , and clinical laboratory tests . Thirty-four patients had ADPKD , and eight had ADPLD . Liver volume decreased by 4.95%+/-6.77 % in the octreotide group but remained practically unchanged ( + 0.92%+/-8.33 % ) in the placebo group ( P=0.048 ) . Among patients with ADPKD , total kidney volume remained practically unchanged ( + 0.25%+/-7.53 % ) in the octreotide group but increased by 8.61%+/-10.07 % in the placebo group ( P=0.045 ) . Changes in GFR were similar in both groups . Octreotide was well tolerated ; treated individuals reported an improved perception of bodily pain and physical activity . In summary , octreotide slowed the progressive increase in liver volume and total kidney volume , improved health perception among patients with PLD , and had an acceptable side effect profile BACKGROUND The course of autosomal dominant polycystic kidney disease ( ADPKD ) is often associated with pain , hypertension , and kidney failure . Pre clinical studies indicated that vasopressin V(2)-receptor antagonists inhibit cyst growth and slow the decline of kidney function . METHODS In this phase 3 , multicenter , double-blind , placebo-controlled , 3-year trial , we r and omly assigned 1445 patients , 18 to 50 years of age , who had ADPKD with a total kidney volume of 750 ml or more and an estimated creatinine clearance of 60 ml per minute or more , in a 2:1 ratio to receive tolvaptan , a V(2)-receptor antagonist , at the highest of three twice-daily dose regimens that the patient found tolerable , or placebo . The primary outcome was the annual rate of change in the total kidney volume . Sequential secondary end points included a composite of time to clinical progression ( defined as worsening kidney function , kidney pain , hypertension , and albuminuria ) and rate of kidney-function decline . RESULTS Over a 3-year period , the increase in total kidney volume in the tolvaptan group was 2.8 % per year ( 95 % confidence interval [ CI ] , 2.5 to 3.1 ) , versus 5.5 % per year in the placebo group ( 95 % CI , 5.1 to 6.0 ; P<0.001 ) . The composite end point favored tolvaptan over placebo ( 44 vs. 50 events per 100 follow-up-years , P=0.01 ) , with lower rates of worsening kidney function ( 2 vs. 5 events per 100 person-years of follow-up , P<0.001 ) and kidney pain ( 5 vs. 7 events per 100 person-years of follow-up , P=0.007 ) . Tolvaptan was associated with a slower decline in kidney function ( reciprocal of the serum creatinine level , -2.61 [ mg per milliliter](-1 ) per year vs. -3.81 [ mg per milliliter](-1 ) per year ; P<0.001 ) . There were fewer ADPKD-related adverse events in the tolvaptan group but more events related to aquaresis ( excretion of electrolyte-free water ) and hepatic adverse events unrelated to ADPKD , contributing to a higher discontinuation rate ( 23 % , vs. 14 % in the placebo group ) . CONCLUSIONS Tolvaptan , as compared with placebo , slowed the increase in total kidney volume and the decline in kidney function over a 3-year period in patients with ADPKD but was associated with a higher discontinuation rate , owing to adverse events . ( Funded by Otsuka Pharmaceuticals and Otsuka Pharmaceutical Development and Commercialization ; TEMPO 3:4 Clinical Trials.gov number , NCT00428948 . ) BACKGROUND AND OBJECTIVES No medical treatment is available for polycystic liver disease , a frequent manifestation of autosomal-dominant polycystic kidney disease ( ADPKD ) . In a prospect i ve , r and omized , double-blind , crossover study , 6 months of octreotide ( 40 mg every 28 days ) therapy limited kidney volume growth more effectively than placebo in 12 patients with ADPKD . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS In this secondary , post hoc analysis of the above study , octreotide-induced changes in liver volumes compared with placebo and the relationship between concomitant changes in liver and kidney volumes were evaluated . Those analyzing liver and kidney volumes were blinded to treatment . RESULTS Liver volumes significantly decreased from 1595 + /- 478 ml to 1524 + /- 453 ml with octreotide whereas they did not appreciably change with placebo . Changes in liver volumes were significantly different between the two treatment periods ( -71 + /- 57 ml versus + 14 + /- 85 ml ) . Octreotide-induced liver volume reduction was fully explained by a reduction in parenchyma volume from 1506 + /- 431 ml to 1432 + /- 403 ml . Changes in liver volumes were significantly correlated with concomitant changes in kidney volumes ( r = 0.67 ) during octreotide but not during placebo treatment . Liver and kidney volume changes significantly differed with both treatments ( octreotide : -71 + /- 57 ml versus + 71 + /- 107 ; placebo : + 14 + /- 85 ml versus + 162 + /- 114 ) , but net reductions in liver ( -85 + /- 103 ml ) and kidney ( -91 + /- 125 ml ) volume growth on octreotide versus placebo were similar . CONCLUSIONS Octreotide therapy reduces liver volumes in patients with ADPKD and is safe Background In a previous trial involving patients with early autosomal dominant polycystic kidney disease ( ADPKD ; estimated creatinine clearance , ≥60 ml per minute ) , the vasopressin V2‐receptor antagonist tolvaptan slowed the growth in total kidney volume and the decline in the estimated glomerular filtration rate ( GFR ) but also caused more elevations in aminotransferase and bilirubin levels . The efficacy and safety of tolvaptan in patients with later‐stage ADPKD are unknown . Methods We conducted a phase 3 , r and omized withdrawal , multicenter , placebo‐controlled , double‐blind trial . After an 8‐week prer and omization period that included sequential placebo and tolvaptan run‐in phases , during which each patient 's ability to take tolvaptan without dose‐limiting side effects was assessed , 1370 patients with ADPKD who were either 18 to 55 years of age with an estimated GFR of 25 to 65 ml per minute per 1.73 m2 of body‐surface area or 56 to 65 years of age with an estimated GFR of 25 to 44 ml per minute per 1.73 m2 were r and omly assigned in a 1:1 ratio to receive tolvaptan or placebo for 12 months . The primary end point was the change in the estimated GFR from baseline to follow‐up , with adjustment for the exact duration that each patient participated ( interpolated to 1 year ) . Safety assessment s were conducted monthly . Results The change from baseline in the estimated GFR was ‐2.34 ml per minute per 1.73 m2 ( 95 % confidence interval [ CI ] , ‐2.81 to ‐1.87 ) in the tolvaptan group , as compared with ‐3.61 ml per minute per 1.73 m2 ( 95 % CI , ‐4.08 to ‐3.14 ) in the placebo group ( difference , 1.27 ml per minute per 1.73 m2 ; 95 % CI , 0.86 to 1.68 ; P<0.001 ) . Elevations in the alanine aminotransferase level ( to > 3 times the upper limit of the normal range ) occurred in 38 of 681 patients ( 5.6 % ) in the tolvaptan group and in 8 of 685 ( 1.2 % ) in the placebo group . Elevations in the aminotransferase level were reversible after stopping tolvaptan . No elevations in the bilirubin level of more than twice the upper limit of the normal range were detected . Conclusions Tolvaptan result ed in a slower decline than placebo in the estimated GFR over a 1‐year period in patients with later‐stage ADPKD . ( Funded by Otsuka Pharmaceuticals and Otsuka Pharmaceutical Development and Commercialization ; REPRISE Clinical Trials.gov number , NCT02160145 . BACKGROUND & AIMS Short-term studies have shown that somatostatin analogues are effective in patients with polycystic kidney and liver disease . We evaluated the long-term effects of long-acting release octreotide ( octreotide LAR ) , a somatostatin inhibitor , vs placebo in these patients . METHODS We performed a controlled study of adults with polycystic kidney and liver disease ( estimated glomerular filtration rate , 40 mL/min/1.73m(2 ) or more ) at a single center in Italy . We analyzed data from 27 patients r and omly assigned to groups given octreotide LAR ( 40 mg , n = 14 ) or placebo ( n = 13 ) each month for 3 years . The primary outcome was absolute and percentage change in total liver volume ( TLV ) , which was measured by magnetic resonance imaging at baseline , after 3 years of treatment , and then 2 years after treatment ended . RESULTS Baseline characteristics were similar between groups . After 3 years , TLV decreased by 130.2 ± 133.2 mL in patients given octreotide LAR ( 7.8 % ± 7.4 % ) ( P = .003 ) but increased by 144.3 ± 316.8 mL ( 6.1 % ± 14.1 % ) in patients given placebo . Change vs baseline differed significantly between groups ( P = .004 ) . Two years after treatment ended , TLV had decreased 14.4 ± 138.4 mL ( 0.8 % ± 9.7 % ) from baseline in patients given octreotide LAR but increased by 224.4 ± 331.7 mL ( 11.0 % ± 14.4 % ) in patients given placebo . Changes vs baseline still differed significantly between groups ( P = .046 ) . Decreases in TLV were similar in each sex ; the change in TLV was greatest among subjects with larger baseline TLV . No patient withdrew because of side effects . CONCLUSIONS In a placebo-controlled study of patients with polycystic kidney and liver disease , 3 years of treatment with octreotide LAR significantly reduced liver volume ; reductions were maintained for 2 years after treatment ended . Octreotide LAR was well-tolerated . Clinical Trials.gov number : NCT02119052 CONTEXT Reduced expression of somatostatin receptors ( SSTRs ) in somatotroph adenomas and their potential down-regulation after medical treatment may explain the unsatisfactory response to octreotide in particular acromegalic patients . The expression of SSTRs other than SSTR2a has not been studied in large , unselected cohorts using novel rabbit monoclonal antibodies . OBJECTIVE We aim ed to determine the expression of SSTRs 1 , 2a , 3 , and 5 in somatotroph adenomas , to correlate expression with clinical characteristics and the response to octreotide , and to ascertain whether preoperative octreotide treatment affected SSTR expression . DESIGN , SETTING , PATIENTS The study included 78 adenomas from patients operated on consecutively during 2000 to 2010 . After exclusion of 13 patients , immunohistochemical analysis with rabbit monoclonal antibodies against SSTRs 1 , 2a , 3 , and 5 ( clones UMB-7 , -1 , -5 , and -4 ) was performed on 65 adenomas . INTERVENTION Twenty-eight patients received preoperative octreotide , and 37 patients were operated on without pretreatment . Twenty-six patients were r and omized to direct surgery ( n = 13 ) or to octreotide pretreatment ( n = 13 ) . MAIN OUTCOME MEASURE SSTR expression was evaluated using a 12- grade scoring system . The responses to the octreotide test dose ( GH reduction ) and to 6 months of octreotide ( IGF-I reduction ) were measured . RESULTS The majority of adenomas showed membranous expression of SSTRs 2a and 5 . SSTR2a expression was reduced in the pretreated group and correlated with the acute octreotide test results and the effect of octreotide treatment . In a linear regression model with SSTR2a expression as the determinant , the correlation with the acute test response improved after adjustment for medical pretreatment . CONCLUSION Rabbit monoclonal antibodies are reliable markers of SSTRs in somatotroph adenomas . SSTR2a expression correlated with the response to octreotide and was reduced after octreotide treatment , indicating the need for adjustment when SSTR2a expression is correlated with baseline characteristics . Evaluation of SSTR subtypes may be an important aspect of improving the medical treatment for acromegaly Background Autosomal dominant polycystic kidney disease ( ADPKD ) is the most frequent genetically determined renal disease . In affected patients , renal function may progressively decline up to end-stage renal disease ( ESRD ) , and approximately 10 % of those with ESRD are affected by ADPKD . The somatostatin analog octreotide long-acting release ( octreotide-LAR ) slows renal function deterioration in patients in early stages of the disease . We evaluated the renoprotective effect of octreotide-LAR in ADPKD patients at high risk of ESRD because of later-stage ADPKD . Methods and findings We did an internally funded , parallel-group , double-blind , placebo-controlled phase III trial to assess octreotide-LAR in adults with ADPKD with glomerular filtration rate ( GFR ) 15–40 ml/min/1.73 m2 . Participants were r and omized to receive 2 intramuscular injections of 20 mg octreotide-LAR ( n = 51 ) or 0.9 % sodium chloride solution ( placebo ; n = 49 ) every 28 days for 3 years . Central r and omization was 1:1 using a computerized list stratified by center and presence or absence of diabetes or proteinuria . Co- primary short- and long-term outcomes were 1-year total kidney volume ( TKV ) ( computed tomography scan ) growth and 3-year GFR ( iohexol plasma clearance ) decline . Analyses were by modified intention-to-treat . Patients were recruited from 4 Italian nephrology units between October 11 , 2011 , and March 20 , 2014 , and followed up to April 14 , 2017 . Baseline characteristics were similar between groups . Compared to placebo , octreotide-LAR reduced median ( 95 % CI ) TKV growth from baseline by 96.8 ( 10.8 to 182.7 ) ml at 1 year ( p = 0.027 ) and 422.6 ( 150.3 to 695.0 ) ml at 3 years ( p = 0.002 ) . Reduction in the median ( 95 % CI ) rate of GFR decline ( 0.56 [ −0.63 to 1.75 ] ml/min/1.73 m2 per year ) was not significant ( p = 0.295 ) . TKV analyses were adjusted for age , sex , and baseline TKV . Over a median ( IQR ) 36 ( 24 to 37 ) months of follow-up , 9 patients on octreotide-LAR and 21 patients on placebo progressed to a doubling of serum creatinine or ESRD ( composite endpoint ) ( hazard ratio [ HR ] [ 95 % CI ] adjusted for age , sex , baseline serum creatinine , and baseline TKV : 0.307 [ 0.127 to 0.742 ] , p = 0.009 ) . One composite endpoint was prevented for every 4 treated patients . Among 63 patients with chronic kidney disease ( CKD ) stage 4 , 3 on octreotide-LAR and 8 on placebo progressed to ESRD ( adjusted HR [ 95 % CI ] : 0.121 [ 0.017 to 0.866 ] , p = 0.036 ) . Three patients on placebo had a serious renal cyst rupture/infection and 1 patient had a serious urinary tract infection/obstruction , versus 1 patient on octreotide-LAR with a serious renal cyst infection . The main study limitation was the small sample size . Conclusions In this study we observed that in later-stage ADPKD , octreotide-LAR slowed kidney growth and delayed progression to ESRD , in particular in CKD stage 4 . Trial registration Clinical Trials.gov NCT01377246 ; EudraCT : 2011 - 000138 - 12 BACKGROUND & AIMS Polycystic liver disease is the most common extrarenal manifestation of autosomal dominant polycystic kidney disease ( ADPKD ) . There is need for robust long-term evidence for the volume-reducing effect of somatostatin analogues . We made use of data from an open-label , r and omized trial to determine the effects of lanreotide on height-adjusted liver volume ( hTLV ) and combined height-adjusted liver and kidney volume ( hTLKV ) in patients with ADPKD . METHODS We performed a 120-week study comparing the reno-protective effects of lanreotide vs st and ard care in 305 patients with ADPKD ( the DIPAK-1 study ) . For this analysis , we studied the 175 patients with polycystic liver disease with hepatic cysts identified by magnetic resonance imaging and liver volume ≥2000 mL. Of these , 93 patients were assigned to a group that received lanreotide ( 120 mg subcutaneously every 4 weeks ) and 82 to a group that received st and ard care ( blood pressure control , a sodium-restricted diet , and antihypertensive agents ) . The primary endpoint was percent change in hTLV between baseline and end of treatment ( week 120 ) . A secondary endpoint was change in hTLKV . RESULTS At 120 weeks , hTLV decreased by 1.99 % in the lanreotide group ( 95 % confidence interval [ CI ] , -4.21 to 0.24 ) and increased by 3.92 % in the control group ( 95 % CI , 1.56 - 6.28 ) . Compared with the control group , lanreotide reduced the growth of hTLV by 5.91 % ( 95 % CI , -9.18 to -2.63 ; P < .001 ) . Growth of hTLV was still reduced by 3.87 % at 4 months after the last injection of lanreotide compared with baseline ( 95 % CI , -7.55 to -0.18 ; P = .04 ) . Lanreotide reduced growth of hTLKV by 7.18 % compared with the control group ( 95 % CI , -10.25 to -4.12 ; P < .001 ) . CONCLUSIONS In this sub analysis of a r and omized trial of patients with polycystic liver disease due to ADPKD , lanreotide for 120 weeks reduced the growth of liver and combined liver and kidney volume . This effect was still present 4 months after the last injection of lanreotide . Clinical Trials.gov , Number : NCT01616927 Importance Autosomal dominant polycystic kidney disease ( ADPKD ) is characterized by progressive cyst formation in both kidneys and loss of renal function , eventually leading to a need for kidney replacement therapy . There are limited therapeutic management options . Objective To examine the effect of the somatostatin analogue lanreotide on the rate of kidney function loss in patients with later-stage ADPKD . Design , Setting , and Participants An open-label r and omized clinical trial with blinded end point assessment that included 309 patients with ADPKD from July 2012 to March 2015 at 4 nephrology outpatient clinics in the Netherl and s. Eligible patients were 18 to 60 years of age and had an estimated glomerular filtration rate ( eGFR ) of 30 to 60 mL/min/1.73 m2 . Follow-up of the 2.5-year trial ended in August 2017 . Interventions Patients were r and omized to receive either lanreotide ( 120 mg subcutaneously once every 4 weeks ) in addition to st and ard care ( n = 153 ) or st and ard care only ( target blood pressure < 140/90 mm Hg ; n = 152 ) . Main Outcomes and Measures Primary outcome was annual change in eGFR assessed as slope through eGFR values during the 2.5-year treatment phase . Secondary outcomes included change in eGFR before vs after treatment , incidence of worsening kidney function ( start of dialysis or 30 % decrease in eGFR ) , change in total kidney volume and change in quality of life ( range : 1 [ not bothered ] to 5 [ extremely bothered ] ) . Results Among the 309 patients who were r and omized ( mean [ SD ] age , 48.4 [ 7.3 ] years ; 53.4 % women ) , 261 ( 85.6 % ) completed the trial . Annual rate of eGFR decline for the lanreotide vs the control group was −3.53 vs −3.46 mL/min/1.73 m2 per year ( difference , −0.08 [ 95 % CI , −0.71 to 0.56 ] ; P = .81 ) . There were no significant differences for incidence of worsening kidney function ( hazard ratio , 0.87 [ 95 % CI , 0.49 to 1.52 ] ; P = .87 ) , change in eGFR ( −3.58 vs −3.45 ; difference , −0.13 mL/min/1.73 m2 per year [ 95 % CI , −1.76 to 1.50 ] ; P = .88 ) , and change in quality of life ( 0.05 vs 0.07 ; difference , −0.03 units per year [ 95 % CI , −0.13 to 0.08 ] ; P = .67 ) . The rate of growth in total kidney volume was lower in the lanreotide group than the control group ( 4.15 % vs 5.56 % ; difference , −1.33 % per year [ 95 % CI , −2.41 % to −0.24 % ] ; P = .02 ) . Adverse events in the lanreotide vs control group included injection site discomfort ( 32 % vs 0.7 % ) , injection site papule ( 5.9 % vs 0 % ) , loose stools ( 91 % vs 6.6 % ) , abdominal discomfort ( 79 % vs 20 % ) , and hepatic cyst infections ( 5.2 % vs 0 % ) . Conclusions and Relevance Among patients with later-stage autosomal dominant polycystic kidney disease , treatment with lanreotide compared with st and ard care did not slow the decline in kidney function over 2.5 years of follow-up . These findings do not support the use of lanreotide for treatment of later-stage autosomal dominant polycystic kidney disease . Trial Registration Clinical Trials.gov Identifier : UNLABELLED Treatment of polycystic liver disease ( PLD ) focuses on symptom improvement . Generic question naires lack sensitivity to capture PLD-related symptoms , a prerequisite to determine effectiveness of therapy . We developed and vali date d a disease-specific question naire that assesses symptoms in PLD ( PLD-Q ) . We identified 16 PLD-related symptoms ( total score 0 - 100 points ) by literature review and interviews with patients and clinicians . The developed PLD-Q was vali date d in Dutch ( n = 200 ) and United States ( US ; n = 203 ) PLD patients . We assessed the correlation of PLD-Q total score with European Organization for Research and Treatment of Cancer ( EORTC ) symptom scale , global health visual analogue scale ( VAS ) of EQ-5D , and liver volume . To test discriminative validity , we compared PLD-Q total scores of patients with different PLD severity stages ( Gigot classification ) and PLD-Q total scores of PLD patients with general controls and polycystic kidney disease patients without PLD . Reproducibility was tested by comparing original test scores with 2-week retest scores . In total , 167 Dutch and 124 US patients returned the question naire . Correlation between PLD-Q total score and EORTC symptom scale ( The Netherl and s [ NL ] , r = 0.788 ; US , r = 0.811 ) and global health VAS ( NL , r = -0.517 ; US , r = -0.593 ) was good . There was no correlation of PLD-Q total score with liver volume ( NL , r = 0.138 ; P = 0.236 ; US , r = 0.254 ; P = 0.052 ) . Gigot type III individuals scored numerically higher than type II patients ( NL , 46 vs. 40 ; P = 0.089 ; US , 48 vs. 36 ; P = 0.055 ) . PLD patients scored higher on the PLD-Q total score than general controls ( NL , 42 vs. 17 ; US , 40 vs. 13 points ) and polycystic kidney disease patients without PLD ( 22 points ) . Reproducibility of PLD-Q was excellent ( NL , r = 0.94 ; US , 0.96 ) . CONCLUSION PLD-Q is a valid , reproducible , and sensitive disease-specific question naire that can be used to assess PLD-related symptoms in clinical care and future research . ( Hepatology 2016;64:151 - 160 ) |
1,278 | 23,307,298 | The predictive value of examining the presence of cervical motor dysfunctions was doubtful .
The course and predictive value of initial reduced cervical mobility was inconsistent .
Cervical motor dysfunctions are present soon after whiplash trauma persisting in those with moderate/severe symptoms .
However , these dysfunctions have limited predictive value , and hence may not explain the complex clinical picture of whiplash-associated disorders . | OBJECTIVE To study the presence of cervical motor dysfunctions in acute whiplash-associated disorders , evaluate their course and assess their predictive value for long-term recovery . | Hypersensitivity to a variety of sensory stimuli is a feature of persistent whiplash associated disorders ( WAD ) . However , little is known about sensory disturbances from the time of injury until transition to either recovery or symptom persistence . Quantitative sensory testing ( pressure and thermal pain thresholds , the brachial plexus provocation test ) , the sympathetic vasoconstrictor reflex and psychological distress ( GHQ‐28 ) were prospect ively measured in 76 whiplash subjects within 1 month of injury and then 2 , 3 and 6 months post‐injury . Subjects were classified at 6 months post‐injury using scores on the Neck Disability Index : recovered ( < 8 ) , mild pain and disability ( 10–28 ) or moderate/severe pain and disability ( > 30 ) . Sensory and sympathetic nervous system tests were also measured in 20 control subjects . All whiplash groups demonstrated local mechanical hyperalgesia in the cervical spine at 1 month post‐injury . This hyperalgesia persisted in those with moderate/severe symptoms at 6 months but resolved by 2 months in those who had recovered or reported persistent mild symptoms . Only those with persistent moderate/severe symptoms at 6 months demonstrated generalised hypersensitivity to all sensory tests . These changes occurred within 1 month of injury and remained unchanged throughout the study period . Whilst no significant group differences were evident for the sympathetic vasoconstrictor response , the moderate/severe group showed a tendency for diminished sympathetic reactivity . GHQ‐28 scores of the moderate/severe group were higher than those of the other two groups . The differences in GHQ‐28 did not impact on any of the sensory measures . These findings suggest that those with persistent moderate/severe symptoms at 6 months display , soon after injury , generalised hypersensitivity suggestive of changes in central pain processing mechanisms . This phenomenon did not occur in those who recover or those with persistent mild symptoms & NA ; Dysfunction in the motor system is a feature of persistent whiplash associated disorders . Little is known about motor dysfunction in the early stages following injury and of its progress in those persons who recover and those who develop persistent symptoms . This study measured prospect ively , motor system function ( cervical range of movement ( ROM ) , joint position error ( JPE ) and activity of the superficial neck flexors ( EMG ) during a test of cranio‐cervical flexion ) as well as a measure of fear of re‐injury ( TAMPA ) in 66 whiplash subjects within 1 month of injury and then 2 and 3 months post injury . Subjects were classified at 3 months post injury using scores on the neck disability index : recovered ( < 8 ) , mild pain and disability ( 10–28 ) or moderate/severe pain and disability ( > 30 ) . Motor system function was also measured in 20 control subjects . All whiplash groups demonstrated decreased ROM and increased EMG ( compared to controls ) at 1 month post injury . This deficit persisted in the group with moderate/severe symptoms but returned to within normal limits in those who had recovered or reported persistent mild pain at 3 months . Increased EMG persisted for 3 months in all whiplash groups . Only the moderate/severe group showed greater JPE , within 1 month of injury , which remained unchanged at 3 months . TAMPA scores of the moderate/severe group were higher than those of the other two groups . The differences in TAMPA did not impact on ROM , EMG or JPE . This study identifies , for the first time , deficits in the motor system , as early as 1 month post whiplash injury , that persisted not only in those reporting moderate/severe symptoms at 3 months but also in subjects who recovered and those with persistent mild symptoms There has been little investigation into whether or not differences exist in the nature of physical impairment associated with neck pain of whiplash and insidious origin . This study examined the neck flexor synergy during performance of the cranio-cervical flexion test , a test targeting the action of the deep neck flexors . Seventy-five volunteer subjects participated in this study and were equally divided between Group 1 , asymptomatic control subjects , Group 2 , subjects with insidious onset neck pain and Group 3 , subjects with neck pain following a whiplash injury . The cranio-cervical flexion test was performed in five progressive stages of increasing cranio-cervical flexion range . Subjects ' performance was guided by feedback from a pressure sensor inserted behind the neck which monitored the slight flattening of the cervical lordosis which occurs with the contraction of longus colli . Myoelectric signals ( EMG ) were detected from the muscles during performance of the test . The results indicated that both the insidious onset neck pain and whiplash groups had higher measures of EMG signal amplitude ( normalized root mean square ) in the sternocleidomastoid during each stage of the test compared to the control subjects ( all P<0.05 ) and had significantly greater shortfalls from the pressure targets in the test stages ( P<0.05 ) . No significant differences were evident between the neck pain groups in either parameter indicating that this physical impairment in the neck flexor synergy is common to neck pain of both whiplash and insidious origin Background : Exposure to a whiplash injury implies a risk for development of chronic disability and h and icap , with reported frequencies ranging from 0 % to 50 % in follow-up studies . The exact risk for development of chronic whiplash syndrome is not known . Objective : To prospect ively determine the sensitivity and specificity of five possible predictors for h and icap following a whiplash injury . Methods : In a 1-year prospect i ve study of persons with acute whiplash injury ( n = 141 ) and control subjects who had acute ankle distortion ( n = 40 ) , pain intensity , number of nonpainful neurologic complaints , cervical mobility , workload during extension and flexion of the neck , and results of psychometric assessment were recorded . The consecutively sample d injured persons were assessed with structured and semistructured question naires , and underwent neurologic examination after 1 week and 1 , 3 , 6 , and 12 months . After 3 to 4 years , participants with whiplash injury were question ed about legal issues . Results : After 1 year , 11 ( 7.8 % ) persons with whiplash injury had not returned to usual level of activity or work . The best single estimator of h and icap was the cervical range-of-motion test , which had a sensitivity of 73 % and a specificity of 91 % ( p < 0.01 , Cox regression analysis ) . Accuracy and specificity increased to 94 % and 99 % when combined with pain intensity and other complaints . This increase was gained at the expense of a reduced sensitivity . Initiation of lawsuit within first month after injury did not influence recovery . Conclusion : The cervical range-of-motion test has a high sensitivity in prediction of h and icap after acute whiplash injury . The value of cervical range-of-motion test is further improved by additional recording of symptoms and pain intensity & NA ; Predictors of outcome following whiplash injury are limited to socio‐demographic and symptomatic factors , which are not readily amenable to secondary and tertiary intervention . This prospect i ve study investigated the predictive capacity of early measures of physical and psychological impairment on pain and disability 6 months following whiplash injury . Motor function ( ROM ; kinaesthetic sense ; activity of the superficial neck flexors ( EMG ) during cranio‐cervical flexion ) , quantitative sensory testing ( pressure , thermal pain thresholds , brachial plexus provocation test ) , sympathetic vasoconstrictor responses and psychological distress ( GHQ‐28 , TSK , IES ) were measured in 76 acute whiplash participants . The outcome measure was Neck Disability Index scores at 6 months . Stepwise regression analysis was used to predict the final NDI score . Logistic regression analyses predicted membership to one of the three groups based on final NDI scores ( < 8 recovered , 10–28 mild pain and disability , > 30 moderate/severe pain and disability ) . Higher initial NDI score ( 1.007–1.12 ) , older age ( 1.03–1.23 ) , cold hyperalgesia ( 1.05–1.58 ) , and acute post‐traumatic stress ( 1.03–1.2 ) predicted membership to the moderate/severe group . Additional variables associated with higher NDI scores at 6 months on stepwise regression analysis were : ROM loss and diminished sympathetic reactivity . Higher initial NDI score ( 1.03–1.28 ) , greater psychological distress ( GHQ‐28 ) ( 1.04–1.28 ) and decreased ROM ( 1.03–1.25 ) predicted subjects with persistent milder symptoms from those who fully recovered . These results demonstrate that both physical and psychological factors play a role in recovery or non‐recovery from whiplash injury . This may assist in the development of more relevant treatment methods for acute whiplash Abstract Higher initial levels of pain and disability , older age , cold hyperalgesia , impaired sympathetic vasoconstriction and moderate post‐traumatic stress symptoms have been shown to be associated with poor outcome 6 months following whiplash injury . This study prospect ively investigated the predictive capacity of these variables at a long‐term follow‐up . Sixty‐five of an initial cohort of 76 acutely injured whiplash participants were followed to 2–3 years post‐accident . Motor function ( ROM ; kinaesthetic sense ; activity of the superficial neck flexors ( EMG ) during cranio‐cervical flexion ) , quantitative sensory testing ( pressure , thermal pain thresholds and brachial plexus provocation test ) , sympathetic vasoconstrictor responses and psychological distress ( GHQ‐28 , TSK and IES ) were measured . The outcome measure was Neck Disability Index ( NDI ) scores . Participants with ongoing moderate/severe symptoms at 2–3 years continued to manifest decreased ROM , increased EMG during cranio‐cervical flexion , sensory hypersensitivity and elevated levels of psychological distress when compared to recovered participants and those with milder symptoms . The latter two groups showed only persistent deficits in cervical muscle recruitment patterns . Higher initial NDI scores ( OR 1.00–1.1 ) , older age ( OR 1.00–1.13 ) , cold hyperalgesia ( OR 1.1–1.13 ) and post‐traumatic stress symptoms ( OR 1.03–1.2 ) remained significant predictors of poor outcome at long‐term follow‐up ( r2 = 0.56 ) . The robustness of these physical and psychological factors suggests that their assessment in the acute stage following whiplash injury will be important BACKGROUND AND PURPOSE Physical mechanisms are the possible factors involved in the development and maintenance of long-term h and icaps after acute whiplash injury . This study prospect ively examined the role of active neck mobility , cervical and extra-cervical pains , as well as non-painful complaints after a whiplash injury as predictors for subsequent h and icap . METHODS Consecutive acute whiplash patients ( n = 688 ) were interviewed and examined by a study nurse after the median of 5 days after injury , and divided into a high- or a low-risk group by an algorithm based on pain intensity , number of non-painful complaints and active neck mobility [ active cervical range of motion ( CROM ) ] . All 458 high-risk patients and 230 low-risk patients received mailed question naires after 3 , 6 and 12 months . Two examiners examined all high-risk patients ( n = 458 ) and 41 consecutive low-risk patients at median 11 , 109 , 380 days after injury . The main outcome measures were : h and icaps , severe headaches , neck pain and neck disability . RESULTS The relative risk for a 1-year disability increased by 3.5 with initial intense neck pain and headaches , by 4.6 times with reduced CROM and by four times with multiple non-painful complaints . CONCLUSION Reduced active neck mobility , immediate intense neck pain and headaches and the presence of multiple non-painful complaints are the important prognostic factors for a 1-year h and icap after acute whiplash Study Design . An experimental study of motor and sensory function and psychological distress in subjects with acute whiplash injury . Objectives . To characterize acute whiplash injury in terms of motor and sensory systems dysfunction and psychological distress and to compare subjects with higher and lesser levels of pain and disability . Summary of Background Data . Motor system dysfunction , sensory hypersensitivity , and psychological distress are present in chronic whiplash associated disorders ( WAD ) , but little is known of such factors in the acute stage of injury . As higher levels of pain and disability in acute WAD are accepted as signs of poor outcome , further characterization of this group from those with lesser symptoms is important . Material s and Methods . Motor function ( cervical range of movement [ ROM ] , joint position error [ JPE ] ; activity of the superficial neck flexors [ EMG ] during a test of cranio-cervical flexion ) , quantitative sensory testing ( pressure , thermal pain thresholds , and responses to the brachial plexus provocation test ) , and psychological distress ( GHQ-28 , TAMPA , IES ) were measured in 80 whiplash subjects ( WAD II or III ) within 1 month of injury , as were 20 control subjects . Results . Three subgroups were identified in the cohort using cluster analysis based on the Neck Disability Index : those with mild , moderate , or severe pain and disability . All whiplash groups demonstrated decreased ROM and increased EMG compared with the controls ( all P < 0.01 ) . Only the moderate and severe groups demonstrated greater JPE and generalized hypersensitivity to all sensory tests ( all P < 0.01 ) . The three whiplash subgroups demonstrated evidence of psychological distress , although this was greater in the moderate and severe groups . Measures of psychological distress did not impact on between group differences in motor or sensory tests . Conclusions . Acute whiplash subjects with higher levels of pain and disability were distinguished by sensory hypersensitivity to a variety of stimuli , suggestive of central nervous system sensitization occurring soon after injury . These responses occurred independently of psychological distress . These findings may be important for the differential diagnosis of acute whiplash injury and could be one reason why those with higher initial pain and disability demonstrate a poorer outcome STUDY DESIGN Clinical measurement , intrarater reliability study . OBJECTIVES To determine the intrarater reliability of cervical active range of motion ( AROM ) measurement of subjects with and without neck pain using the cervical range-of-motion device ( CROM ) . BACKGROUND Cervical spine AROM data are used by physical therapists to assist in identifying movement impairment , monitor patient progress , and evaluate the effectiveness of intervention . Presently , insufficient literature exists regarding the intrarater reliability of cervical AROM measurements using the CROM . METHODS AND MEASURES Twenty-five adult subjects without neck pain and 22 adult subjects with neck pain volunteered for the study . Two trials of cervical AROM measurement ( 6 movements ) were performed for each subject . Practice sessions , methods of measurement , and rest time between trials were st and ardized ; order of measurement was r and omized . RESULTS The intraclass correlation coefficients ( ICC3,1 ) for the subjects without neck pain ranged from 0.87 for flexion ( 95 % confidence interval [ CI ] : 0.76 - 0.95 ) to 0.94 for left rotation ( 95 % CI : 0.87 - 0.97 ) . The st and ard error of the measurement ranged from 2.3 degrees to 4.0 degrees . The ICCs for the subjects with neck pain ranged from 0.88 for flexion ( 95 % CI : 0.73 - 0.95 ) to 0.96 for left rotation ( 95 % CI : 0.91 - 0.98 ) . The st and ard error of the measurement ranged from 2.5 degrees to 4.1 degrees . Minimal detectable change ranged from 5.4 degrees for left rotation in the subjects without neck pain to 9.6 degrees for flexion in the subjects with neck pain . CONCLUSION Intrarater reliability for cervical AROM measurement of persons with and without neck pain is sufficient to consider use of the CROM in clinical practice , although changes between 5 degrees to 10 degrees are needed to feel confident that a real change in spine mobility has occurred OBJECTIVE To investigate the reliability and discriminative ability of a new test design ed to detect accuracy of neck movements . DESIGN Repeated- measures . Case-control . SETTING University musculoskeletal research clinic in Icel and . PARTICIPANTS Twenty women ( mean age + /- st and ard deviation [ SD ] , 30.8+/-9.1 y ; range , 18 - 49 y ) with chronic whiplash-associated disorders ( WAD ) grade s I and II ( duration , 6 mo-6 y ) , with current pain score on a visual analog scale of 46.8+/-21.8 , and a disability score on the Northwick Park Neck Pain Disability Index of 45%+/-14 % . Twenty asymptomatic women ( mean age + /- SD , 29.3+/-8.6 y ; range , 18 - 48 y ) with no history of whiplash or insidious onset neck pain served as controls . INTERVENTION A slowly moving object appeared on a computer screen and traced an unpredictable movement path that the subjects were required to follow by moving their heads . Three r and omly ordered movement patterns were tested . MAIN OUTCOME MEASURE A new software program connected to a 3Space Fastrak system was used to measure the mean absolute error ( in millimeters ) of 3 trials in each movement pattern . RESULTS The mean differences ( + /-2 SD ) between days 1 and 2 were.01+/-.64 mm for the asymptomatic group and .33+/-1.80 mm for the WAD group . The between-day intraclass correlation coefficients were between.60 and .77 for the asymptomatic group and .79 and .86 for the WAD group . Repeated- measures analysis of variance revealed a significant difference between groups ( P=.02 ) . The Tukey post hoc test showed significant between-group differences for each movement pattern ( P</=.05 ) . In each successive trial , a slight improvement for the asymptomatic group and a slight worsening for the WAD group were detected . CONCLUSIONS Better reliability was detected for the asymptomatic group than for the WAD group . The test could discriminate between the asymptomatic group versus the chronic WAD group Transition from acute whiplash injury to either recovery or chronicity and the development of chronic whiplash-associated disorders ( WAD ) remains a challenging issue for research ers and clinicians . The roles of social support and personality traits in long-term functioning following whiplash have not been studied concomitantly . The present study aim ed to examine whether social support and personality traits are related to long-term functioning following whiplash . One hundred forty-three subjects , who had experienced a whiplash injury in a traffic accident 10–26 months before the study took place , participated . The initial diagnoses were a ‘ sprain of the neck ’ ( ICD-9 code 847.0 ) ; only the outcome of grade s I – III acute WAD was studied . Long-term functioning was considered within the biopsychosocial model : it was expressed in terms of disability , functional status , quality of life and psychological well-being . Participants filled out a set of question naires to measure the long-term functioning parameters ( i.e. the Neck Disability Index , Medical Outcome Study Short-Form General Health Survey , Anamnestic Comparative Self- Assessment measure of overall well-being and the Symptom Checklist-90 ) and potential determinants of long-term functioning ( the Dutch Personality Question naire and the Social Support List ) . The results suggest that social support ( especially the discrepancies dimension of social support ) and personality traits ( i.e. inadequacy , self-satisfaction and resentment ) are related to long-term functioning following whiplash injury ( Spearman rho varied between 0.32 and 0.57 ; p < 0.01 ) . Within the discrepancy dimension , everyday emotional support , emotional support during problems , appreciative support and informative support were identified as important correlates of long-term functioning . Future prospect i ve studies are required to confirm the role of social support and personality traits in relation to long-term functioning following whiplash . For such studies , a broad view of long-term functioning within the biopsychological model should be applied Study Design . A 6-month prospect i ve study of neck mobility in patients with acute whiplash injury and a control group with acute ankle distortion was conducted . Objectives . To assess active neck mobility after acute whiplash and ankle distortion injuries , and to relate neck mobility to headache , neck pain , and speed of car at the time of collision . Summary of background data . A major problem after whiplash injury is restriction of neck mobility immediately subsequent to trauma . It is , however , unclear whether neck mobility changes after the acute injury are related to the associated headache and neck pain . Methods . Cervical range of neck motion , neck pain , and headache were assessed after 1 week , then 1 , 3 , and 6 months after injury in 141 patients with acute whiplash injury , and in 40 patients with acute nonsport ankle distortion . Results . Patients with whiplash injury had significantly reduced flexion , extension , lateral flexion , and rotation of the neck immediately after injury , as compared with patients with ankle distortion injury . Neck mobility , however , was similar in the two groups after 3 months . In patients with whiplash injury , neck pain and neck mobility were found to be related inversely to reported headache and neck mobility . Neck mobility was not significantly related to a difference in car speed at the time of collision . Conclusions . Neck mobility is reduced immediately after , but not 3 months after , a whiplash trauma . Headache and neck mobility are related inversely and neck pain and neck mobility are related inversely during the first 6 months after acute whiplash injury Study Design . Test-retest and case-control study design ed to detect accuracy of cervical spine movements by comparing 3 incrementally difficult movement patterns . An asymptomatic group , a nontrauma neck pain group , and a group with whiplash-associated disorders , Grade II , were tested ( n = 18 in each group ) . Objective . To determine the test-retest reliability and the discriminative validity of the new Fly method . Summary of Background Data . A lack of reliable and valid measures for grading the deficits of movement control in the cervical spine makes it impossible to prescribe treatment appropriate to each patient 's respective impairment level . Methods . Head tracking of a moving fly which appeared on a computer screen . Easy , medium , and difficult patterns , each of which was repeated 3 times in r and om order , were tested . Amplitude accuracy ( deviation of movements ) , directional accuracy ( time on target , undershoots vs. overshoots ) were compared across patterns and groups on 2 occasions , 1 week apart . Results . The intraclass correlation coefficient2,1 ranged from 0.53 to 0.82 for both variables , except for the subvariable “ overshoots ” ( 0.14–0.42 ) . The limits of agreement ( LOA ) were progressively wider across patterns ( easy – medium – difficult ) and groups ( asymptomatic – nontrauma – whiplash-associated disorder ) . Analysis of variance with repeated measures revealed significant differences between patterns within each group and between groups respectively for both outcome variables ( P < 0.001 ) . Conclusion . The Fly method provides reliable and valid measures for movement control of the cervical spine . Higher means and wider LOA across patterns and subject groups are reasoned to be inherent in the new Fly method and the subject groups tested . The wide LOA in the symptomatic groups supports the development of a normative data base . The new Fly method can be used both as an assessment and a treatment method and ensures gradual progression in the treatment for deficits of movement control in patients with neck pain A longitudinal study was conducted to observe persons with neck pain after motor vehicle collisions . The aims were to reveal the prospect i ve development of cervical kinaesthesia and to investigate the association between the test results and self-reported pain and disabilities . Two different cervical kinaesthetic tests , the Fly test and the Head-Neck Relocation test , measured movement control and the relocation accuracy of the cervical spine , respectively . Self- assessment measures included pain intensity ( VAS ) , neck pain and disability ( NDI ) , fear of re-injury ( TAMPA ) and psychological distress ( GHQ-28 ) . Seventy-four subjects entered the study , but 47 were eligible , as they participated in all 4 measurements at 1 , 3 , 6 and 12 months post-collision . According to the performances on the two kinaesthetic tests , the subjects could be classified into improvement and non-improvement groups , respectively . The result revealed , for the first time , two different courses of deficient cervical kinaesthesia . About half of the participants showed significant deteriorating performances in both kinaesthetic tests throughout the year ( p < 0.002 ) , while the other half improved their performances ( p < 0.02 ) . Generally , the relationships between the kinaesthetic tests and the self- assessment scores were not significant , irrespective of the performances on the two kinaesthetic tests . Accordingly , the results of the question naires correlated poorly or weakly with the kinaesthetic test results at all assessment points . The need for developing a new question naire , capturing the symptoms prevalent in patients with neck pain and cervical sensorimotor impairments is urgent . What determines the two different kinaesthetic courses need to be scrutinised in future research & NA ; The objective of our prospect i ve inception cohort study was to identify prognostic factors for poor recovery in patients with whiplash‐associated disorders grade 1 or 2 who still had neck pain and accompanying complaints 2 weeks after the accident . The study was carried out in a primary health care setting in The Netherl and s and included 125 patients . The primary outcome measure was functional recovery defined in terms of neck pain intensity or work disability without medication use . The secondary outcome measures included neck pain intensity , work disability and sick leave . The outcomes were assessed at 4 , 12 and 52 weeks after the accident . Prognostic factors were identified by logistic regression analyses . One year after the injury , 64 % of the patients were recovered . Factors related to poor recovery were female gender , a low level of education , high initial neck pain , more severe disability , higher levels of somatisation and sleep difficulties . Neck pain intensity and work disability proved to be the most consistent predictors for poor recovery . The accuracy of the predictions of the prognostic models was high , meaning that the models adequately distinguished patients with poor recovery from those regarded as recovered . These findings add to the growing body of evidence , indicating that socio‐demographic , physical and psychological factors affect short‐ and long‐term outcome after whiplash injury . Our findings also indicate that care providers can easily identify patients at risk for poor recovery with a visual analogue scale for initial pain intensity and work‐related activities Definition : To what extent does the study allow us to draw conclusions about a causal effect between two or more constructs ? Issues : Selection , maturation , history , mortality , testing , regression towrd the mean , selection by maturation , treatment by mortality , treatment by testing , measured treatment variables Increase : Eliminate the threats , above all do experimental manipulations , r and om assignment , and counterbalancing Study Design . One-year prospect i ve study of 141 acute whiplash patients ( WLP ) and 40 acute ankle-injured controls . Objective . This study investigates a priori determined potential risk factors to develop a risk assessment tool , for which the expediency was examined . Summary of Background Data . The whiplash-associated disorders ( WAD ) grading system that emerged from The Quebec Task-Force-on-Whiplash has been of limited value for predicting work-related recovery and for explaining biopsychosocial disability after whiplash and new predictive factors , for example , risk criteria that comprehensively differentiate acute WLP in a biopsychosocial manner are needed . Methods . Consecutively , 141 acute WLP and 40 ankle-injured recruited from emergency units were examined after 1 week , 1 , 3 , 6 , and 12 months obtaining neck/head visual analog scale score , number of nonpainful complaints , epidemiological , social , psychological data and neurological examination , active neck mobility , and furthermore muscle tenderness and pain response , and strength and duration of neck muscles . Risk factors derived ( reduced cervical range of motion , intense neck pain/headache , multiple nonpain complaints ) were applied in a risk assessment score and divided into seven risk strata . Results . A receiver operating characteristics curve for the Risk Assessment Score and 1-year work disability showed an area of 0.90 . Risk strata and number of sick days showed a log-linear relationship . In stratum 1 full recovery was encountered , but for high-risk patients in stratum 6 only 50 % and 7 only 20 % had returned to work after 1 year ( P < 5.4 × 10−5 ) . Strength measures , psychophysical pain measurements , and psychological and social data ( reported elsewhere ) showed significant relation to risk strata . Conclusion . The Risk Assessment score is suggested as a valuable tool for grading WLP early after injury . It has reasonable screening power for encountering work disability and reflects the biopsychosocial nature of whiplash injuries Head repositioning accuracy ( HRA ) after full range active motion was evaluated in 60 cervicalgic patients . The mean angular error was 7.7 degrees + /- 3.3 ( mean + /- SD ) and 82 % were outside a threshold value of 4.5 degrees . After r and omization 30 patients followed a rehabilitation program based on eye-head coupling ( RG ) and 30 served as a control group ( CG ) . At 10 week follow-up , a greater gain in HRA was observed in the RG ( 2 degrees + /- 2.7 , mean + /- SD ) than in the CG ( 0 + /- 2.6 , mean + /- SD ) ( p = 0.005 ) . Clinical parameters ( pain , drug intake , range of motion , and self assessed functional improvement ) were also more improved in the RG than in the CG . These data emphasize the role of a neck proprioception alteration in chronic neck pain and suggest that a rehabilitation program based on eye-head coupling should be included in most medical management of cervicalgic patients Objective : To compare head relocation accuracy in traumatic ( whiplash ) , insidious onset neck pain patients and asymptomatic subjects when targeting a natural head posture ( NHP ) and complex predetermined positions . Design : A case – control study . Setting : University-based musculoskeletal research clinic . Participants : Sixty-three volunteers divided into three groups of similar gender and age : Group 1 ( n = 21 ) an asymptomatic group ; group 2 ( n = 20 ) insidious onset neck pain ; group 3 ( n = 22 ) a history of whiplash injury . Intervention : Five r and omly ordered tests design ed to detect relocation accuracy of the head . Outcome measures : A 3-Space Fastrak system measured the mean absolute relocation error of three trials of each relocation test . Results : A significant difference was found between groups in one of the tests targeting the NHP ( p = 0.001 ) . Post-hoc pairwise comparisons revealed a significant difference ( p £ 0.05 ) between the asymptomatic group and each symptomatic group . The difference between the symptomatic groups just failed to reach significance ( p = 0.07 ) . None of the other four tests revealed significant differences . Conclusion : The test of targeting the NHP indicates that relocation inaccuracy exists in patients with neck pain with a trend to suggest that the deficit may be greater in whiplash patients . Tests employing unfamiliar postures or more complex movement were not successful in differentiating subject groups |
1,279 | 27,814,776 | The associations between lower compared with higher caloric intake and primary and secondary outcomes , including pneumonia , were not different between caloric restriction and non-caloric restriction trials , except for the hospital stay which was longer with lower caloric intake in the caloric restriction trials .
Conclusions We found no association between the dose of caloric intake in adult critically ill patients and hospital mortality .
Lower caloric intake was associated with lower risk of blood stream infections and incident renal replacement therapy ( five trials only ) . | Background There is conflicting evidence about the relationship between the dose of enteral caloric intake and survival in critically ill patients .
The objective of this systematic review and meta- analysis is to compare the effect of lower versus higher dose of enteral caloric intake in adult critically ill patients on outcome . | OBJECTIVE To compare the efficacy of combination therapy , with erythromycin and metoclopramide , to erythromycin alone in the treatment of feed intolerance in critically ill patients . DESIGN R and omized , controlled , double-blind trial . SETTING Mixed medical and surgical intensive care unit . PATIENTS Seventy-five mechanically ventilated , medical patients with feed intolerance ( gastric residual volume ≥250 mL ) . INTERVENTIONS Patients received either combination therapy ( n = 37 ; 200 mg of intravenous erythromycin twice daily + 10 mg of intravenous metoclopramide four times daily ) or erythromycin alone ( n = 38 ; 200 mg of intravenous erythromycin twice daily ) in a prospect i ve , r and omized fashion . Gastric feeding was re-commenced and 6-hourly gastric aspirates performed . Patients were studied for 7 days . Successful feeding was defined as a gastric residual volume < 250 mL with the feeding rate ≥40 mL/hr , over 7 days . Secondary outcomes included daily caloric intake , vomiting , postpyloric feeding , length of stay , and mortality . MEASUREMENTS AND MAIN RESULTS Demographic data ; use of inotropes , opioids , or benzodiazepines ; and pretreatment gastric residual volume were similar between the two groups . The gastric residual volume was significantly lower after 24 hrs of treatment with combination therapy , compared with erythromycin alone ( 136 ± 23 mL vs. 293 ± 45 mL , p = .04 ) . Over the 7 days , patients treated with combination therapy had greater feeding success , received more daily calories , and had a lower requirement for postpyloric feeding , compared with erythromycin alone . Tachyphylaxis occurred in both groups but was less with combination therapy . Sedation , higher pretreatment gastric residual volume , and hypoalbuminemia were significantly associated with a poor response . There was no difference in the length of hospital stay or mortality rate between the groups . Watery diarrhea was more common with combination therapy ( 20 of 37 vs. 10 of 38 , p = .01 ) but was not associated with enteric infections , including Clostridium difficile . CONCLUSIONS In critically ill patients with feed intolerance , combination therapy with erythromycin and metoclopramide is more effective than erythromycin alone in improving the delivery of nasogastric nutrition and should be considered as the first-line treatment . ( Crit Care Med . 2007;35:2561 - 2567 . ) NQ Nguyen , M Chapman , RJ Fraser , LK Bryant , C Burgstad , RH Holloway Introduction : Our aim was to evaluate the impact of hyperproteic hypocaloric enteral feeding on clinical outcomes in critically ill patients , particularly on severity of organic failure measured with the Sequential Organ Failure Assessment ( SOFA ) . Material s and Methods : In a double blind clinical trial , 80 critically ill adult patients were r and omized to hyperproteic hypocaloric or to isocaloric enteral nutrition ; all patients completed follow-up of at least 4 days . Prescribed caloric intake was : Hyperproteic hypocaloric enteral nutrition ( 15 kcal/kg with 1.7 g/kg of protein ) or isocaloric enteral nutrition ( 25 kcal/kg with 20 % of the calories as protein ) . The main outcome was the differences in delta SOFA at 48 h. Secondary outcomes were intensive care unit ( ICU ) length of stay , days on ventilator , hyperglycemic events , and insulin requirements . Results : There were no differences in SOFA score at baseline ( 7.5 ( st and ard deviation ( SD ) 2.9 ) vs 6.7 ( SD 2.5 ) P = 0.17 ) . The total amount of calories delivered was similarly low in both groups ( 12 kcal/kg in intervention group vs 14 kcal/kg in controls ) , but proteic delivery was significantly different ( 1.4 vs 0.76 g/kg , respectively P ≤ 0.0001 ) . The intervention group showed an improvement in SOFA score at 48 h ( delta SOFA 1.7 ( SD 1.9 ) vs 0.7 ( SD 2.8 ) P = 0.04 ) and less hyperglycemic episodes per day ( 1.0 ( SD 1.3 ) vs 1.7 ( SD 2.5 ) P = 0.017 ) . Discussion : Enteral hyperproteic hypocaloric nutrition therapy could be associated with a decrease in multiple organ failure measured with SOFA score . We also found decreased hyperglycemia and a trend towards less mechanical ventilation days and ICU length of stay This document represents the first collaboration between 2 organizations — the American Society for Parenteral and Enteral Nutrition and the Society of Critical Care Medicine — to describe best practice s in nutrition therapy in critically ill children . The target of these guidelines is intended to be the pediatric critically ill patient ( > 1 month and 2–3 days in a PICU admitting medical , surgical , and cardiac patients . In total , 2032 citations were scanned for relevance . The PubMed / MEDLINE search result ed in 960 citations for clinical trials and 925 citations for cohort studies . The EMBASE search for clinical trials culled 1661 citations . In total , the search for clinical trials yielded 1107 citations , whereas the cohort search yielded 925 . After careful review , 16 r and omized controlled trials and 37 cohort studies appeared to answer 1 of the 8 preidentified question groups for this guideline . We used the GRADE criteria ( Grading of Recommendations , Assessment , BACKGROUND Despite extensive use of enteral ( EN ) and parenteral nutrition ( PN ) in intensive care unit ( ICU ) population s for 4 decades , evidence to support their efficacy is extremely limited . METHODS A prospect i ve r and omized trial was conducted evaluate the impact on outcomes of intensive medical nutrition therapy ( IMNT ; provision of > 75 % of estimated energy and protein needs per day via EN and adequate oral diet ) from diagnosis of acute lung injury ( ALI ) to hospital discharge compared with st and ard nutrition support care ( SNSC ; st and ard EN and ad lib feeding ) . The primary outcome was infections ; secondary outcomes included number of days on mechanical ventilation , in the ICU , and in the hospital and mortality . RESULTS Overall , 78 patients ( 40 IMNT and 38 SNSC ) were recruited . No significant differences between groups for age , body mass index , disease severity , white blood cell count , glucose , C-reactive protein , energy or protein needs occurred . The IMNT group received significantly higher percentage of estimated energy ( 84.7 % vs 55.4 % , P < .0001 ) and protein needs ( 76.1 vs 54.4 % , P < .0001 ) per day compared with SNSC . No differences occurred in length of mechanical ventilation , hospital or ICU stay , or infections . The trial was stopped early because of significantly greater hospital mortality in IMNT vs SNSC ( 40 % vs 16 % , P = .02 ) . Cox proportional hazards models indicated the hazard of death in the IMNT group was 5.67 times higher ( P = .001 ) than in the SNSC group . CONCLUSIONS Provision of IMNT from ALI diagnosis to hospital discharge increases mortality BACKGROUND Nutritional support has been recognized as an essential part of intensive care unit management . However , the appropriate caloric intake for critically ill patients remains ill defined . OBJECTIVE We examined the effect of permissive underfeeding compared with that of target feeding and of intensive insulin therapy ( IIT ) compared with that of conventional insulin therapy ( CIT ) on the outcomes of critically ill patients . DESIGN This study had a 2 × 2 factorial , r and omized , controlled design . Eligible patients were r and omly assigned to permissive underfeeding or target feeding groups ( caloric goal : 60 - 70 % compared with 90 - 100 % of calculated requirement , respectively ) with either IIT or CIT ( target blood glucose : 4.4 - 6.1 compared with 10 - 11.1 mmol/L , respectively ) . RESULTS Twenty-eight-day all-cause mortality was 18.3 % in the permissive underfeeding group compared with 23.3 % in the target feeding group ( relative risk : 0.79 ; 95 % CI : 0.48 , 1.29 ; P = 0.34 ) . Hospital mortality was lower in the permissive underfeeding group than in the target group ( 30.0 % compared with 42.5 % ; relative risk : 0.71 ; 95 % CI : 0.50 , 0.99 ; P = 0.04 ) . No significant differences in outcomes were observed between the IIT and CIT groups . CONCLUSION In critically ill patients , permissive underfeeding may be associated with lower mortality rates than target feeding . This trial was registered at controlled-trials.com as IS RCT N96294863 IMPORTANCE Monitoring of residual gastric volume is recommended to prevent ventilator-associated pneumonia ( VAP ) in patients receiving early enteral nutrition . However , studies have challenged the reliability and effectiveness of this measure . OBJECTIVE To test the hypothesis that the risk of VAP is not increased when residual gastric volume is not monitored compared with routine residual gastric volume monitoring in patients receiving invasive mechanical ventilation and early enteral nutrition . DESIGN , SETTING , AND PATIENTS R and omized , noninferiority , open-label , multicenter trial conducted from May 2010 through March 2011 in adults requiring invasive mechanical ventilation for more than 2 days and given enteral nutrition within 36 hours after intubation at 9 French intensive care units ( ICUs ) ; 452 patients were r and omized and 449 included in the intention-to-treat analysis ( 3 withdrew initial consent ) . INTERVENTION Absence of residual gastric volume monitoring . Intolerance to enteral nutrition was based only on regurgitation and vomiting in the intervention group and based on residual gastric volume greater than 250 mL at any of the 6 hourly measurements and regurgitation or vomiting in the control group . MAIN OUTCOME MEASURES Proportion of patients with at least 1 VAP episode within 90 days after r and omization , as assessed by an adjudication committee blinded to patient group . The prestated noninferiority margin was 10 % . RESULTS In the intention-to-treat population , VAP occurred in 38 of 227 patients ( 16.7 % ) in the intervention group and in 35 of 222 patients ( 15.8 % ) in the control group ( difference , 0.9 % ; 90 % CI , -4.8 % to 6.7 % ) . There were no significant between-group differences in other ICU-acquired infections , mechanical ventilation duration , ICU stay length , or mortality rates . The proportion of patients receiving 100 % of their calorie goal was higher in the intervention group ( odds ratio , 1.77 ; 90 % CI , 1.25 - 2.51 ; P = .008 ) . Similar results were obtained in the per- protocol population . CONCLUSION AND RELEVANCE Among adults requiring mechanical ventilation and receiving early enteral nutrition , the absence of gastric volume monitoring was not inferior to routine residual gastric volume monitoring in terms of development of VAP . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01137487 Introduction To compare outcomes from early post-pyloric to gastric feeding in ventilated , critically ill patients in a medical intensive care unit ( ICU ) . Methods Prospect i ve r and omized study . Ventilated patients were r and omly assigned to receive enteral feed via a nasogastric or a post-pyloric tube . Post-pyloric tubes were inserted by the bedside nurse and placement was confirmed radiographically . Results A total of 104 patients were enrolled , 54 in the gastric group and 50 in the post-pyloric group . Bedside post-pyloric tube insertion was successful in 80 % of patients . Patients who failed post-pyloric insertion were fed via the nasogastric route , but were analysed on an intent-to treat basis . A per protocol analysis was also performed . Baseline characteristics were similar for all except Acute Physiology and Chronic Health Evaluation II ( APACHE II ) score , which was higher in the post-pyloric group . There was no difference in length of stay or ventilator days . The gastric group was quicker to initiate feed 4.3 hours ( 2.9 - 6.5 hours ) as compared to post-pyloric group 6.6 hours ( 4.5 - 13.0 hours ) ( P = 0.0002 ) . The time to reach target feeds from admission was also faster in gastric group : 8.7 hours ( 7.6 - 13.0 hours ) compared to 12.3 hours ( 8.9 - 17.5 hours ) . The average daily energy and protein deficit were lower in gastric group 73 Kcal ( 2 - 288 Kcal ) and 3.5 g ( 0 - 15 g ) compared to 167 Kcal ( 70 - 411 Kcal ) and 6.5 g ( 2.8 - 17.3 g ) respectively but was only statistically significant for the average energy deficit ( P = 0.035 ) . This difference disappeared in the per protocol analysis . Complication rates were similar . Conclusions Early post-pyloric feeding offers no advantage over early gastric feeding in terms of overall nutrition received and complicationsTrial Registration Clinical Trial : anzctr.org.au : A prospect i ve study was carried out over a 10-month period to compare nutritional status , gastric colonization , and rates of nosocomial pneumonia in intensive care unit ( ICU ) patients r and omized to either gastric tube feeding or feeding by an endoscopically placed jejunal tube . Sixty-nine patients were considered eligible for the study . Thirty-eight patients were enrolled from medical and surgical ICUs at two hospitals and were equally divided into two groups . The groups were similar in age , sex , race , underlying disease , type of surgical procedure , number of days fed , duration of ICU stay , duration of mechanical ventilation , days with fever , and days of antibiotic therapy . The jejunal tube ( JT ) group had more patients who were in circulatory shock on admission ( 79 % ) than the gastric feeding ( GT ) group ( 68.4 % ) . Additionally , the JT group had higher Acute Physiology Scores ( 24.0 vs 21.7 ) and fewer patients with pneumonia at the time of entry into the study ( 26.3 % us 31.6 % ) . The JT patients received a signi BACKGROUND Enteral nutrition ( EN ) is recommended for patients in the intensive-care unit ( ICU ) , but it does not consistently achieve nutritional goals . We assessed whether delivery of 100 % of the energy target from days 4 to 8 in the ICU with EN plus supplemental parenteral nutrition ( SPN ) could optimise clinical outcome . METHODS This r and omised controlled trial was undertaken in two centres in Switzerl and . We enrolled patients on day 3 of admission to the ICU who had received less than 60 % of their energy target from EN , were expected to stay for longer than 5 days , and to survive for longer than 7 days . We calculated energy targets with indirect calorimetry on day 3 , or if not possible , set targets as 25 and 30 kcal per kg of ideal bodyweight a day for women and men , respectively . Patients were r and omly assigned ( 1:1 ) by a computer-generated r and omisation sequence to receive EN or SPN . The primary outcome was occurrence of nosocomial infection after cessation of intervention ( day 8) , measured until end of follow-up ( day 28 ) , analysed by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00802503 . FINDINGS We r and omly assigned 153 patients to SPN and 152 to EN . 30 patients discontinued before the study end . Mean energy delivery between day 4 and 8 was 28 kcal/kg per day ( SD 5 ) for the SPN group ( 103 % [ SD 18 % ] of energy target ) , compared with 20 kcal/kg per day ( 7 ) for the EN group ( 77 % [ 27 % ] ) . Between days 9 and 28 , 41 ( 27 % ) of 153 patients in the SPN group had a nosocomial infection compared with 58 ( 38 % ) of 152 patients in the EN group ( hazard ratio 0·65 , 95 % CI 0·43 - 0·97 ; p=0·0338 ) , and the SPN group had a lower mean number of nosocomial infections per patient ( -0·42 [ -0·79 to -0·05 ] ; p=0·0248 ) . INTERPRETATION Individually optimised energy supplementation with SPN starting 4 days after ICU admission could reduce nosocomial infections and should be considered as a strategy to improve clinical outcome in patients in the ICU for whom EN is insufficient . FUNDING Foundation Nutrition 2000Plus , ICU Quality Funds , Baxter , and Fresenius Kabi 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 CONTEXT Responses to critical illness , such as excessive inflammation and hyperglycemia , may trigger detrimental chain reactions that damage cellular proteins and organelles . Such responses to illness contribute to the risk of ( nonresolving ) multiple organ dysfunction and adverse outcome . OBJECTIVE We studied autophagy as a bulk degradation pathway able to remove toxic protein aggregates and damaged organelles and how these are affected by preventing hyperglycemia with insulin during critical illness . DESIGN AND SETTING Patients participated in a r and omized study , conducted at a university hospital surgical/medical intensive care unit . PATIENTS We studied adult prolonged critically ill patients vs. controls . INTERVENTIONS Tolerating excessive hyperglycemia was compared with intensive insulin therapy targeting normoglycemia . MAIN OUTCOME MEASURES We quantified (ultra)structural abnormalities and hepatic and skeletal muscle protein levels of key players in autophagy . RESULTS Morphologically , both liver and muscle revealed an autophagy-deficiency phenotype . Proteins involved in initiation and elongation steps of autophagy were induced 1.3- to 6.5-fold by critical illness ( P ≤ 0.01 ) , but mature autophagic vacuole formation was 62 % impaired ( P = 0.05 ) and proteins normally de grade d by autophagy accumulated up to 97-fold ( P ≤ 0.03 ) . Mitophagy markers were unaltered or down-regulated ( P = 0.05 ) . Although insulin preserved hepatocytic mitochondrial integrity ( P = 0.05 ) , it further reduced the number of autophagic vacuoles by 80 % ( P = 0.05 ) . CONCLUSIONS Insufficient autophagy in prolonged critical illness may cause inadequate removal of damaged proteins and mitochondria . Such incomplete clearance of cellular damage , inflicted by illness and aggravated by hyperglycemia , could explain lack of recovery from organ failure in prolonged critically ill patients . These data open perspectives for therapies that activate autophagy during critical illness BACKGROUND This study compared an intermittent feeding regimen ( one-sixth of daily needs infused every 4 hours ) with a continuous ( drip ) feeding regimen for critically ill trauma patients . There were two outcome variables : time to reach goal volume and the days on 100 % of caloric needs via an enteral route in the first 10 days of the intensive care unit stay . Adverse events were also tallied . METHODS A prospect i ve r and omized trial was conducted in the trauma intensive care unit in a university Level I trauma center . A total of 164 trauma patients , 18 years of age and older were admitted to the trauma intensive care unit with a noninjured gastrointestinal tract and required more than 48 hours of mechanical ventilation . Patients were r and omized to receive enteral nutrition via an intermittent feeding regimen versus a continuous feeding regimen . A single nutritionist calculated caloric and protein goals . A strict protocol was followed where hourly enteral intake , interruptions and their causes , diarrhea , and pneumonia were recorded , as well as st and ard guidelines for intolerance . RESULTS A total of 164 patients were r and omized and 139 reached their calculated nutritional goal within 7 days . There were no statistical differences in complications of tube feeding . The patients intermittently fed reached the goal faster and by day 7 had a higher probability of being at goal than did the patients fed continuously ( chi = 6.01 , p = 0.01 ) . Intermittent patients maintained 100 % of goal for 4 of 10 days per patient ( 95 % CI = 3.5 - 4.4 ) as compared with the drip arm goal for only 3 of 10 days per patient ( 95 % CI = 2.7 - 3.6 ) . CONCLUSIONS Patients from both the intermittent and continuous feeding regimens reached the goal during the study period of 7 days but the intermittent regimen patients reached goal enteral calories earlier . The intermittent gastric regimen is logistically simple and has equivalent outcomes to a st and ard drip-feeding regimen OBJECTIVES To assess the consistency of caloric intake with American College of Chest Physicians ( ACCP ) recommendations for critically ill patients and to evaluate the relationship of caloric intake with clinical outcomes . DESIGN Prospect i ve cohort study . SETTING Adult intensive care units ( ICUs ) at 2 teaching hospitals . PARTICIPANTS Patients with an ICU length of stay of at least 96 hours . MEASUREMENTS AND RESULTS On ICU admission , severity of illness ( ie , simplified acute physiology score II ) and markers of nutritional status ( ie , serum albumin level and body mass index ) were recorded . The route of feeding ( ie , enteral or parenteral ) , actual caloric intake ( ie , percentage of ACCP recommendations : 0 % to 32 % [ tertile I ] ; 33 % to 65 % [ tertile II ] ; ≥66 % [ tertile III ] ) , and evidence of GI intolerance ( ie , gastric aspirate levels , ≥100 mL ) were recorded daily . The following outcomes were assessed : status on hospital discharge ( alive vs dead ) ; spontaneous ventilation before ICU discharge ( yes vs no ) ; and ICU discharge without developing nosocomial sepsis ( yes vs no ) . The average caloric intake among 187 participants was 50.6 % of the ACCP targets and was similar in both hospitals . Caloric intake was inversely related to the mean number of gastric aspirates≥ 100 mL/d ( Spearman ρ = -.04 ; p = .06 ) , but not to severity of illness , nutritional status , or route of feeding . After accounting for the number of gastric aspirates ≥100 mL , severity of illness , nutritional status , and route of feeding , tertile II of caloric intake ( vs tertile I ) was associated with a significantly greater likelihood of achieving spontaneous ventilation before ICU discharge . Tertile III of caloric intake ( vs tertile I ) was associated with a significantly lower likelihood of both hospital discharge alive and spontaneous ventilation before ICU discharge . CONCLUSIONS Study participants were underfed relative to ACCP targets . These targets , however , may overestimate needs because moderate caloric intake ( ie , 33 % to 65 % of ACCP targets ; approximately 9 to 18 kcal/kg per day ) was associated with better outcomes than higher levels of caloric intake BACKGROUND Early enteral feeding has been shown to be beneficial in improving outcome in critically injured trauma patients . Delayed gastric emptying occurs frequently in trauma patients , increasing the time to achieve nutritional goals , and limiting the benefit of early enteral feedings . Intravenous erythromycin is an effective agent for improving gastric motility in diabetics and postgastrectomy patients . The purpose of this study is to determine the effectiveness of erythromycin for improving gastric motility in critically injured trauma patients . METHODS All critically injured patients who received gastric feedings within 72 hours of admission were c and i date s for the study . Those patients who failed to tolerate feedings at 48 hours ( gastric residual > 150 mL ) were eligible for enrollment . Patients were prospect ively assigned to two treatment groups by r and omization to receive either erythromycin ( ERY ) or placebo ( PLA ) . Treatment was continued in patients who tolerated gastric feedings until the feedings were no longer required . Patients with continued intolerance for 48 hours after r and omization were considered failures of therapy and given metoclopramide . RESULTS Sixty-eight patients were enrolled and were well matched for age , sex , and Injury Severity Score . Mortality , intensive care unit length of stay , hospital length of stay , number of ventilator days , and rate of nosocomial infections were similar in each group . There was a significant difference between the ERY group and the PLA group in the amount of feedings tolerated at 48 hours ( 58 % vs. 44 % , p = 0.001 ) . There was no difference in the amount of feedings tolerated ( as a percentage of target goal volume ) throughout the entire duration of the study ( ERY [ 65 % of target ] vs. PLA [ 59 % ] , p = 0.061 ) . Overall success of therapy at 48 hours was 56 % in the ERY group versus 39 % in the PLA group , but this also did not reach statistical significance ( p = 0.22 ) . CONCLUSION Intravenous erythromycin improves gastric motility and enhances early nutritional intake in critically injured patients Objective : To determine whether medical intensive care unit ( ICU ) patients receiving nasoduodenal ( ND ) feedings achieve optimal nutritional support and better clinical outcomes compared with patients receiving nasogastric ( NG ) feedings . Design : A prospect i ve , r and omized , clinical study . Setting : Medical ICU of a university-affiliated tertiary medical center . Patients : One hundred twenty-one medical ICU patients required enteral feeding . Interventions : Patients were r and omized to receive enteral feeding . One group received ND feedings and the other group received NG feedings . All patients followed the same protocol . Measurements and Main Results : The primary outcome of optimal nutritional support was assessed by measurement of time to goal tube feed rate and daily calorie and protein intake . Secondary clinical outcomes included number of ICU , hospital and ventilator days , number of the days in the study , blood – glucose levels , incidence of vomiting , diarrhea , gastrointestinal bleeding , tube replaced , tube clogged , fever , bacteremia , and ventilator-associated pneumonia ( VAP ) , and mortality rate . Results showed that the ND group had a higher average daily calorie and protein intake compared with NG group and achieved nutritional goals earlier . In terms of clinical outcomes , patients in the ND group had a lower rate of vomiting and VAP . The other clinical outcomes such as number of ICU days , hospital days , ventilator days , blood – glucose level , tube replaced or clogged , diarrhea , gastrointestinal bleeding , fever , bacteremia , and mortality rate were not significantly different between two groups . Conclusions : Patients who received ND feedings achieved nutritional goals earlier than those who received NG feeding . ND feeding group also has a lower rate of vomiting and VAP in the medical ICU setting Objective To compare the incidence of enteral nutrition-related gastrointestinal complications , the efficacy of diet administration , and the incidence of nosocomial pneumonia in patients fed in the stomach or in the jejunum . Design Prospect i ve , r and omized multicenter study . Setting Intensive care units ( ICUs ) in 11 teaching hospitals . Patients Critically ill patients who could receive early enteral nutrition more than 5 days . Interventions Enteral nutrition was started in the first 36 hrs after admission . One group was fed with a nasogastric tube ( GEN group ) and the other in the jejunum through a dual-lumen nasogastrojejunal tube ( JEN group ) . Measurements and Main Results Gastrointestinal complications were previously defined . The efficacy of diet administration was calculated using the volume ratio ( expressed as the ratio between administered and prescribed volumes ) . Nosocomial pneumonia was defined according the Centers for Disease Control and Prevention ’s definitions . One hundred ten patients were included ( GEN : 51 , JEN : 50 ) . Both groups were comparable in age , gender , Acute Physiology and Chronic Health Evaluation II , and Multiple Organ Dysfunction Score . There were no differences in feeding duration , ICU length of stay , or mortality ( 43 % vs. 38 % ) . The JEN group had lesser gastrointestinal complications ( 57 % vs. 24 % , p < .001 ) , mainly because of a lesser incidence of increased gastric residuals ( 49 % vs. 2 % , p < .001 ) . Volume ratio was similar in both groups . A post hoc analysis showed that the JEN group had a higher volume ratio at day 7 than the GEN group ( 68 % vs. 82 % , p < .03 ) in patients from ICUs with previous experience in jejunal feeding . Both groups had a similar incidence of nosocomial pneumonia ( 40 % vs. 32 % ) . Conclusions Gastrointestinal complications are less frequent in ICU patients fed in the jejunum . Nevertheless , it seems to be a necessary learning curve to achieve better results with a postpyloric access . Early enteral nutrition using a nasojejunal route seems not to be an efficacious measure to decrease nosocomial pneumonia in critically ill patients OBJECTIVE To observe the impact of the diverse caloric energy intake on the outcomes and occurrence rate of complications in septic patients . METHODS A prospect i ve single-blind r and omized controlled trial was conducted . 158 cases of septic patients in intensive care unit ( ICU ) were enrolled and r and omly assigned to three groups according to their different target value of nutrition : group A [ measurements of resting energy expenditure ( MREE ) < 90 % J , B ( MREE 90%-110 % ) and C ( MREE > 110 % ) . The caloric intake , mechanical ventilation duration ( MVD),nosocomial infection rate , 28-day and 60-day mortality were analyzed . RESULTS Daily energy intake in 7 days after ICU admission was as follows : the difference in target value of nutrition ( kJ/d : 7 075.0 ± 1 046.5 , 5 667.8 ± 1 908.8,4 428.8 ± 1 377.8 ) , calory intake ( k]/d : 4 671.6 ± 1 205.6 , 5 655.3 ± 1 373.0 , 6 053.0 ± 1 557.2 ) , enteral nutrition value ( kJ/d : 2 051.1 ± 1 046.5 , 3 980.9 ± 1 586.5 , 5 337.1 ± 2 921.8 ) and average intake rate [ ( 66.0 ± 15.8 ) % , ( 100.0 ± 5.7 ) % , ( 134.0 ± 19.7)% J , and they were statistically significant difference among A , B , C groups ( all P<0.05 ) . The parenteral nutrition in group C were much higher than that in group A and group B ( kJ/d : 2 055.3 ± 273.4vs . 427.0 ± 273.4 , 473.0 ± 332.0 , both P<0.05 ) . The calories provided by glucose and diprivan were similar among three groups . The MVD and ICU stay were shorter in group B than that in groups A and C [ MVD ( days ) : 8.4 ± 6.3 vs.11.0 ± 8.2 , 17.8 ± 13.0 , P>0.05 and P<0.05 ; ICU stay ( days ) : 11.0 ± 6.4 vs. 14.9 ± 9.6 , 17.8 ± 13.0 , respectively , P>0.05 and P<0.05 ] . The total hospital stay ( days : 32.0 ± 22.5 , 26.8 ± 7.0 , 30.4 ± 21.4 ) and nosocomial infection rate [ 91.1 % ( 51156 ) , 84.0 % ( 42/50 ) , 90.4 % ( 4 7/52 ) J were similar among A , B , C groups ( all P>0.05 ) . There was no difference in survival rate at 28 days among three groups as shown by the Kaplan-Meier survival curve ( F=3.145,P=0.076 ) . The survival rate at 60 days showed a tendency of lowering in groups A and C , especially in group C ( F=9.284 , P=0.010 ) . CONCLUSION Both higher and lower caloric energy intake may be associated with an adverse impact , but appropriate caloric intake would improve the outcome and reduce the complication rate in septic patients BACKGROUND AND OBJECTIVE Unguided nasojejunal feeding tube insertion success rates are low . Controversy persists about how to safely and efficiently perform enteral nutrition ( EN ) in critically ill patients . This study explores an innovative blind nasointestinal tube ( NIT ) insertion method and compares nasogastric and nasointestinal feeding . METHODS Seventy critically ill patients admitted to the intensive care unit ( ICU ) were divided r and omly into a nasogastric tube group ( NGT ; n=35 ) and an NIT group ( NIT ; n=35 ) . After bedside NGT and blind-type NIT insertion , tube position was assessed and EN was started on day 1 . Patients ' nutritional status parameters , mechanical ventilation duration , average ICU stay , nutritional support costs , and feeding complications were compared . RESULTS Pre-albumin and transferrin levels on days 7 and 14 were significantly higher in the NIT group than in the NGT group ( p<0.01 , p<0.05 ) . Bloating , diarrhea , upper gastrointestinal bleeding , and liver damage did not differ significantly between groups ( p>0.05 ) . Interleukin-6 and tumor necrosis factor-α levels and APACHE II score were significantly lower in the NIT group than in the NGT group ( p<0.01 , p<0.05 ) . Reflux and pneumonia incidences , mechanical ventilation duration , average ICU stay length , and nutritional support costs were significantly lower in the NIT group than in the NGT group ( p<0.01 ) . CONCLUSION Blind bedside NIT insertion is convenient and its use can effectively improve nutritional status , reduce feeding complications , and decrease nutritional support costs of critically ill patients Introduction Current practice in the delivery of caloric intake ( DCI ) in patients with severe acute kidney injury ( AKI ) receiving renal replacement therapy ( RRT ) is unknown . We aim ed to describe calorie administration in patients enrolled in the R and omized Evaluation of Normal vs. Augmented Level of Replacement Therapy ( RENAL ) study and to assess the association between DCI and clinical outcomes . Methods We performed a secondary analysis in 1456 patients from the RENAL trial . We measured the dose and evolution of DCI during treatment and analyzed its association with major clinical outcomes using multivariable logistic regression , Cox proportional hazards models , and time adjusted models . Results Overall , mean DCI during treatment in ICU was low at only 10.9 ± 9 Kcal/kg/day for non-survivors and 11 ± 9 Kcal/kg/day for survivors . Among patients with a lower DCI ( below the median ) 334 of 729 ( 45.8 % ) had died at 90-days after r and omization compared with 316 of 727 ( 43.3 % ) patients with a higher DCI ( above the median ) ( P = 0.34 ) . On multivariable logistic regression analysis , mean DCI carried an odds ratio of 0.95 ( 95 % confidence interval ( CI ) : 0.91 - 1.00 ; P = 0.06 ) per 100 Kcal increase for 90-day mortality . DCI was not associated with significant differences in renal replacement ( RRT ) free days , mechanical ventilation free days , ICU free days and hospital free days . These findings remained essentially unaltered after time adjusted analysis and Cox proportional hazards modeling . Conclusions In the RENAL study , mean DCI was low . Within the limits of such low caloric intake , greater DCI was not associated with improved clinical outcomes .Trial registration Clinical Trials.gov number , Abstract Background There is much controversy around the optimal caloric intake in intensive care unit ( ICU ) patients , based on the diverging results of prospect i ve studies . Therefore , we assessed the presence of an association between caloric intake and outcome in a large cohort included in the Glucontrol study . Methods Patients ( n = 1004 ) were divided into four quartiles ( q1–q4 ) according to the daily caloric intake ( n = 251/quartile ) . ICU , hospital and 28-day mortality and the length of stay ( LOS ) in ICU and in the hospital were compared between each quartile , before and after adjustment in case of differences in baseline characteristics . Results Caloric intake averaged 0.5 ± 0.6 ( q1 ) , 3.0 ± 0.7 ( q2 ) , 13.4 ± 5.1 ( q3 ) and 32.4 ± 8.5 ( q4 ) kcal/kg/day ( p < 0.001 between quartiles ) . Comparisons among quartiles revealed that ICU , hospital and 28-day mortality were lower in q2 than in the other quartiles . ICU and hospital LOS were lower in q1 and q2 . After adjustment for age , type of admission and severity scores , hospital mortality was lower in q2 than in the other quartiles , and LOS was lower in q1 and q2 than in q3–q4 . Conclusions In this large and heterogeneous cohort of ICU short stayers , a J-shaped relationship between the amount of calories provided and outcome was found . These hypothesis generating findings are consistent with the concept of improved clinical outcome by early energy restriction . Trial registration # : Clinical Trials.gov # NCT00107601 , EUDRA-CT Number : BACKGROUND The provision of nutritional support for patients in intensive care units ( ICUs ) varies widely both within and between institutions . We tested the hypothesis that evidence -based algorithms to improve nutritional support in the ICU would improve patient outcomes . METHODS A cluster-r and omized controlled trial was performed in the ICUs of 11 community and 3 teaching hospitals between October 1997 and September 1998 . Hospital ICUs were stratified by hospital type and r and omized to the intervention or control arm . Patients at least 16 years of age with an expected ICU stay of at least 48 hours were enrolled in the study ( n = 499 ) . Evidence -based recommendations were introduced in the 7 intervention hospitals by means of in-service education sessions , reminders ( local dietitian , posters ) and academic detailing that stressed early institution of nutritional support , preferably enteral . RESULTS Two hospitals crossed over and were excluded from the primary analysis . Compared with the patients in the control hospitals ( n = 214 ) , the patients in the intervention hospitals ( n = 248 ) received significantly more days of enteral nutrition ( 6.7 v. 5.4 per 10 patient-days ; p = 0.042 ) , had a significantly shorter mean stay in hospital ( 25 v. 35 days ; p = 0.003 ) and showed a trend toward reduced mortality ( 27 % v. 37 % ; p = 0.058 ) . The mean stay in the ICU did not differ between the control and intervention groups ( 10.9 v. 11.8 days ; p = 0.7 ) . INTERPRETATION Implementation of evidence -based recommendations improved the provision of nutritional support and was associated with improved clinical outcomes Objective : To determine whether nasal bridling is a low-morbidity practice that decreases feeding tube dislodgment and results in improved caloric intake . Design : R and omized , controlled trial . Setting : Private , tertiary-care referral center . Patients : A total of 80 surgical intensive care unit patients requiring nasojejunal feeding . Intervention : Nasal bridling of feeding tubes . Measurements and Main Results : Between January 1 , 2008 and July 31 , 2008 , 80 patients were r and omized to have their nasojejunal feeding tubes secured with either a nasal bridle or an adhesive device . Baseline characteristics examined included age , sex , concurrent nasogastric tube presence , primary diagnosis , Acute Physiology and Chronic Health Evaluation III score , need for mechanical ventilation , need for emergent surgery , Riker Sedation Score , and Glascow Coma Scale . Patients were monitored daily for prevalence and cause of feeding tube removal , percentage of goal calories received , nasal ulceration , and sinusitis . Serum albumin and prealbumin levels were collected weekly . All patients were examined , using an intention-to-treat design . Except for a higher prevalence of emergent surgery in the bridled patients , the bridled and unbridled groups had no difference in baseline characteristics . Bridled tubes were less likely to be unintentionally dislodged than unbridled tubes ( 18 % vs. 63 % , p < .0001 ) result ing in bridled patients receiving a higher percentage of goal calories ( median 78 % [ interquartile range , 65%–86 % ] vs. 62 % [ interquartile range , 47%–80 % ] , p = .016 ) than unbridled patients . There were five cases of mild epistaxis upon bridle insertion and four cases of superficial nasal ulceration associated with the bridle . No bridled patients were diagnosed with sinusitis during the study period . Serum albumin and prealbumin levels did not differ between the groups . Conclusions : Bridling of nasoenteric feeding tubes in critically ill patients is a low-morbidity practice that reduces the rate of unintentional tube dislodgment and may result in improved caloric intake BACKGROUND Proper caloric intake goals in critically ill surgical patients are unclear . It is possible that overnutrition can lead to hyperglycemia and an increased risk of infection . OBJECTIVE This study was conducted to determine whether surgical infection outcomes in the intensive care unit ( ICU ) could be improved with the use of hypocaloric nutritional support . DESIGN Eighty-three critically ill patients were r and omly allocated to receive either the st and ard calculated daily caloric requirement of 25 - 30 kcal · kg(-1 ) · d(-1 ) ( eucaloric ) or 50 % of that value ( hypocaloric ) via enteral tube feeds or parenteral nutrition , with an equal protein allocation in each group ( 1.5 g · kg(-1 ) · d(-1 ) ) . RESULTS There were 82 infections in the hypocaloric group and 66 in the eucaloric group , with no significant difference in the mean ( ± SE ) number of infections per patient ( 2.0 ± 0.6 and 1.6 ± 0.2 , respectively ; P = 0.50 ) , percentage of patients acquiring infection [ 70.7 % ( 29 of 41 ) and 76.2 % ( 32 of 42 ) , respectively ; P = 0.57 ] , mean ICU length of stay ( 16.7 ± 2.7 and 13.5 ± 1.1 d , respectively ; P = 0.28 ) , mean hospital length of stay ( 35.2 ± 4.9 and 31.0 ± 2.5 d , respectively ; P = 0.45 ) , mean 0600 glucose concentration ( 132 ± 2.9 and 135 ± 3.1 mg/dL , respectively ; P = 0.63 ) , or number of mortalities [ 3 ( 7.3 % ) and 4 ( 9.5 % ) , respectively ; P = 0.72 ] . Further analyses revealed no differences when analyzed by sex , admission diagnosis , site of infection , or causative organism . CONCLUSIONS Among critically ill surgical patients , caloric provision across a wide acceptable range does not appear to be associated with major outcomes , including infectious complications . The optimum target for caloric provision remains elusive BACKGROUND Amyotrophic lateral sclerosis is a fatal neurodegenerative disease with few therapeutic options . Mild obesity is associated with greater survival in patients with the disease , and calorie-dense diets increased survival in a mouse model . We aim ed to assess the safety and tolerability of two hypercaloric diets in patients with amyotrophic lateral sclerosis receiving enteral nutrition . METHODS In this double-blind , placebo-controlled , r and omised phase 2 clinical trial , we enrolled adults with amyotrophic lateral sclerosis from participating centres in the USA . Eligible participants were aged 18 years or older with no history of diabetes or liver or cardiovascular disease , and who were already receiving percutaneous enteral nutrition . We r and omly assigned participants ( 1:1:1 ) using a computer-generated list of r and om numbers to one of three dietary interventions : replacement calories using an isocaloric tube-fed diet ( control ) , a high-carbohydrate hypercaloric tube-fed diet ( HC/HC ) , or a high-fat hypercaloric tube-fed diet ( HF/HC ) . Participants received the intervention diets for 4 months and were followed up for 5 months . The primary outcomes were safety and tolerability , analysed in all patients who began their study diet . This trial is registered with Clinical Trials.gov , number NCT00983983 . FINDINGS Between Dec 14 , 2009 , and Nov 2 , 2012 , we enrolled 24 participants , of whom 20 started their study diet ( six in the control group , eight in the HC/HC group , and six in the HF/HC group ) . One patient in the control group , one in the HC/HC group , and two in the HF/HC group withdrew consent before receiving the intervention . Participants who received the HC/HC diet had a smaller total number of adverse events than did those in the other groups ( 23 in the HC/HC group vs 42 in the control group vs 48 in the HF/HC group ; overall , p=0.06 ; HC/HC vs control , p=0.06 ) and significantly fewer serious adverse events than did those on the control diet ( none vs nine ; p=0.0005 ) . Fewer patients in the HC/HC group discontinued their study diet due to adverse events ( none [ 0 % ] of eight in the HC/HC group vs three [ 50 % ] of six in the control group ) . During the 5 month follow-up , no deaths occurred in the nine patients assigned to the HC/HC diet compared with three deaths ( 43 % ) in the seven patients assigned to the control diet ( log-rank p=0.03 ) . Adverse events , tolerability , deaths , and disease progression did not differ significantly between the HF/HC group and the control group . INTERPRETATION Our results provide preliminary evidence that hypercaloric enteral nutrition is safe and tolerable in patients with amyotrophic lateral sclerosis , and support the study of nutritional interventions in larger r and omised controlled trials at earlier stages of the disease . FUNDING Muscular Dystrophy Association , National Center for Research Re sources , National Institutes of Health , and Harvard NeuroDiscovery Center Objective : To determine the effect of a low-calorie parenteral nutrition ( PN ) regimen on the incidence and severity of hyperglycemia and insulin requirements . Design : Prospect i ve , r and omized , clinical trial . Setting : Urban , university-affiliated , level-I trauma center . Patients : Consecutive surgical patients requiring PN . Interventions : Patients were r and omized to receive either a low-calorie PN formulation ( 20 nonprotein kilocalories per kg per day ) or a st and ard PN formulation ( 30 nonprotein kilocalories per kg per day ) . Lipid-derived calories were st and ardized to 1000 kilocalories three times weekly for all patients ; consequently , the number of calories varied only by the amount of carbohydrate administered . Protein requirements were individualized on the basis of estimated metabolic stress . Hyperglycemia was defined as a blood glucose level ≥200 mg/dL. Measurements and Main Results : Forty patients were evaluated ( low-calorie PN , n = 20 ; st and ard PN , n = 20 ) . Demographics of the two groups were similar . The incidence of hyperglycemic events was significantly lower in the low-calorie group ( 0 % [ 0–0.5 ] vs. 33.1 % [ 0–58.4 ] ; p = .001 ] . Additionally , the severity of hyperglycemia was also lower in the low-calorie group ( mean glucose area under the curve = 118 ± 22 [mg·hr]/dL vs. 172 ± 44 [mg·hr]/dL ; p < .001 ) . This result ed in lower average daily insulin requirements ( 0 [ 0–0 ] units vs. 10.9 [ 0–25.6 ] units ; p < .001 . ) . The only predictor of hyperglycemia was a dextrose administration rate > 4 mg/kg/min . Conclusions : Administration of a low-calorie PN formulation result ed in fewer and less-severe hyperglycemic events and lower insulin requirements . PN regimens should not exceed a dextrose administration rate of 4 mg/kg/min to avoid hyperglycemic events BACKGROUND The optimal amount and type of fat in the nutrition support of burned patients have not been determined . The aim of this study was to test low-fat nutritional solutions , with or without fish oil , on protein metabolism , morbidity , and length of care in severely burned adults . METHODS In a prospect i ve r and omized clinical trial , 43 patients were assigned to one of the following groups : control ( 35 % fat ) , low-fat solution ( ie , 15 % of total calories as fat ) , low-fat with fish oil , given for 30 days . Nitrogen balance , urinary 3-methylhistidine excretion , urinary cortisol , and clinical status were measured daily . Corticosteroid-binding globulin and total and free serum cortisol were measured every 3 days . RESULTS Compared with controls , patients on low-fat support had fewer cases of pneumonia : 3/24 vs 7/13 ( p = .02 ) , better respiratory and nutrition status , and shorter time to healing : 1.2 vs 1.8 days/% burned area ( p = 0.01 ) . There was no difference in nitrogen balance between groups , and 3-methylhistidine excretion was higher and serum free cortisol was lower in log-fat -- fed patients than in controls . There was no difference between the two low-fat groups in any of the parameters measured . CONCLUSIONS This study showed that low-fat nutrition support decreases infectious morbidity and shortens length of stay in burn patients . Fish oil does not seem to add clinical benefit to low-fat solutions . In addition , this study provides the first evidence that nutrition intervention modulates cortisol-binding globulin and the concentration of free circulating cortisol after a severe stress BACKGROUND AND AIMS Critically ill patients with complicated evolution are frequently hypermetabolic , catabolic , and at risk of underfeeding . The study aim ed at assessing the relationship between energy balance and outcome in critically ill patients . METHODS Prospect i ve observational study conducted in consecutive patients staying > or = 5 days in the surgical ICU of a University hospital . Demographic data , time to feeding , route , energy delivery , and outcome were recorded . Energy balance was calculated as energy delivery minus target . Data in means+/-SD , linear regressions between energy balance and outcome variables . RESULTS Forty eight patients aged 57+/-16 years were investigated ; complete data are available in 669 days . Mechanical ventilation lasted 11+/-8 days , ICU stay 15+/-9 was days , and 30-days mortality was 38 % . Time to feeding was 3.1+/-2.2 days . Enteral nutrition was the most frequent route with 433 days . Mean daily energy delivery was 1090+/-930 kcal . Combining enteral and parenteral nutrition achieved highest energy delivery . Cumulated energy balance was between -12,600+/-10,520 kcal , and correlated with complications ( P < 0.001 ) , already after 1 week . CONCLUSION Negative energy balances were correlated with increasing number of complications , particularly infections . Energy debt appears as a promising tool for nutritional follow-up , which should be further tested . Delaying initiation of nutritional support exposes the patients to energy deficits that can not be compensated later on 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 Purpose To determine whether nutritional support guided by repeated measurements of resting energy requirements improves the outcome of critically ill patients . Methods This was a prospect i ve , r and omized , single-center , pilot clinical trial conducted in an adult general intensive care ( ICU ) unit . The study population comprised mechanically ventilated patients ( n = 130 ) expected to stay in ICU more than 3 days . Patients were r and omized to receive enteral nutrition ( EN ) with an energy target determined either ( 1 ) by repeated indirect calorimetry measurements ( study group , n = 56 ) , or ( 2 ) according to 25 kcal/kg/day ( control group , n = 56 ) . EN was supplemented with parenteral nutrition when required . Results The primary outcome was hospital mortality . Measured pre- study resting energy expenditure ( REE ) was similar in both groups ( 1,976 ± 468 vs. 1,838 ± 468 kcal , p = 0.6 ) . Patients in the study group had a higher mean energy ( 2,086 ± 460 vs. 1,480 ± 356 kcal/day , p = 0.01 ) and protein intake ( 76 ± 16 vs. 53 ± 16 g/day , p = 0.01 ) . There was a trend towards an improved hospital mortality in the intention to treat group ( 21/65 patients , 32.3 % vs. 31/65 patients , 47.7 % , p = 0.058 ) whereas length of ventilation ( 16.1 ± 14.7 vs. 10.5 ± 8.3 days , p = 0.03 ) and ICU stay ( 17.2 ± 14.6 vs. 11.7 ± 8.4 , p = 0.04 ) were increased . Conclusions In this single-center pilot study a bundle comprising actively supervised nutritional intervention and providing near target energy requirements based on repeated energy measurements was achievable in a general ICU and may be associated with lower hospital mortality Objective : Enteral nutrition is provided to mechanically ventilated patients who can not eat normally , yet the amount of support needed is unknown . We conducted this r and omized , open-label study to test the hypothesis that initial low-volume ( i.e. , trophic ) enteral nutrition would decrease episodes of gastrointestinal intolerance/complications and improve outcomes as compared to initial full-energy enteral nutrition in patients with acute respiratory failure . Design : R and omized , open-label study . Patients : A total of 200 patients with acute respiratory failure expected to require mechanical ventilation for at least 72 hrs . Interventions : Patients were r and omized to receive either initial trophic ( 10 mL/hr ) or full-energy enteral nutrition for the initial 6 days of ventilation . Measurements and Main Results : The primary outcome measure was ventilator-free days to day 28 . Baseline characteristics were similar between the 98 patients r and omized to trophic and the 102 patients r and omized to full-energy nutrition . At enrollment , patients had a mean Acute Physiology and Chronic Health Evaluation II score of 26.9 and a Pao2/Fio2 ratio of 182 and 38 % were in shock . Both groups received similar duration s of enteral nutrition ( 5.5 vs. 5.1 days ; p = .51 ) . The trophic group received an average of 15.8 % ± 11 % of goal calories daily through day 6 compared to 74.8 % ± 38.5 % ( p < .001 ) for the full-energy group . Both groups had a median of 23.0 ventilator-free days ( p = .90 ) and a median of 21.0 intensive-care-unit-free days ( p = .64 ) . Mortality to hospital discharge was 22.4 % for the trophic group vs. 19.6 % for the full-energy group ( p = .62 ) . In the first 6 days , the trophic group had trends for less diarrhea ( 19 % vs. 24 % of feeding days ; p = .08 ) and significantly fewer episodes of elevated gastric residual volumes ( 2 % vs. 8 % of feeding days ; p < .001 ) . Conclusion : Initial trophic enteral nutrition result ed in clinical outcomes in mechanically ventilated patients with acute respiratory failure similar to those of early full-energy enteral nutrition but with fewer episodes of gastrointestinal intolerance Objective : The optimal amount of calories required by critically ill patients continues to be controversial . The objective of this study is to examine the relationship between the amount of calories administered and mortality . Design : Prospect i ve , multi-institutional audit . Setting : Three hundred fifty-two intensive care units from 33 countries . Patients : A total of 7,872 mechanically ventilated , critically ill patients who remained in the intensive care unit for at least 96 hrs . Interventions : None . Measurements and Main Results : We evaluated the association between the amount of calories received and 60-day hospital mortality using various sample restriction and statistical adjustment techniques and demonstrate the influence of the analytic approach on the results . In the initial unadjusted analysis , we observe a significant association between increased caloric intake and increased mortality ( odds ratio 1.28 ; 95 % confidence interval 1.12–1.48 for patients receiving more than two-thirds of their caloric prescription vs. those receiving less than one-third of their prescription ) . Excluding days after permanent progression to oral intake attenuated the estimates of harm ( unadjusted analysis : odds ratio 1.04 ; 95 % confidence interval 0.90–1.20 ) . Restricting the analysis to patients with at least 4 days in the intensive care unit before progression to oral intake and excluding days of observation after progression to oral intake result ed in a significant benefit to increased caloric intake ( unadjusted odds ratio 0.73 ; 95 % confidence interval 0.63–0.85 ) . When further adjusting for both evaluable days and other important covariates , patients who received more than two-thirds of their caloric prescription are much less likely to die than those receiving less than one-third of their prescription ( odds ratio 0.67 ; 95 % confidence interval 0.56–0.79 ; p < .0001 ) . When treated as a continuous variable , the overall association between the percent of the caloric prescription received and mortality is highly statistically significant with increasing calories associated with decreasing mortality ( p < .0001 ) . Conclusions : The estimated association between the amount of calories and mortality is significantly influenced by the statistical methodology used . The most appropriate available analyses suggest that attempting to meet caloric targets may be associated with improved clinical outcomes in critically ill patients Objective : Increasing evidence implicates mitochondrial dysfunction as an early , important event in the pathogenesis of critical illness-induced multiple organ failure . We previously demonstrated that prevention of hyperglycemia limits damage to mitochondria in vital organs , thereby reducing morbidity and mortality . We now hypothesize that inadequate activation of mitochondrial repair processes ( clearance of damaged mitochondria by autophagy , mitochondrial fusion/fission , and biogenesis ) may contribute to accumulation of mitochondrial damage , persistence of organ failure , and adverse outcome of critical illness . Design : Prospect i ve , r and omized studies in a critically ill rabbit model . Setting : University laboratory . Subjects : Three-month-old male rabbits . Interventions : We studied whether vital organ mitochondrial repair pathways are differentially affected in surviving and nonsurviving hyperglycemic critically ill animals in relation to mitochondrial and organ damage . Next , we investigated the impact of preventing hyperglycemia over time and of administering rapamycin as an autophagy activator . Measurements and Main Results : In both liver and kidney of hyperglycemic critically ill rabbits , we observed signs of insufficient autophagy , including accumulation of p62 and a concomitant decrease in the microtubule-associated protein light-chain-3-II/microtubule-associated protein light-chain-3-I ratio . The phenotype of insufficient autophagy was more pronounced in nonsurviving than in surviving animals . Molecular markers of insufficient autophagy correlated with impaired mitochondrial function and more severe organ damage . In contrast , key players in mitochondrial fusion/fission or biogenesis were not significantly different regarding survival status . Therefore , we focused on autophagy to study the impact of preventing hyperglycemia . Both after 3 and 7 days of illness , autophagy was better preserved in normoglycemic than in hyperglycemic rabbits , which correlated with improved mitochondrial function and less organ damage . Stimulation of autophagy in kidney with rapamycin correlated with protection of renal function . Conclusions : Our findings put forward insufficient autophagy as a potentially important contributor to mitochondrial and organ damage in critical illness and open perspectives for therapies that activate autophagy during critical illness & NA ; Both gastric and duodenal feeding tubes are used to provide enteral nutrition . Most studies comparing the two methods have focused primarily on rates of complications , rather than on nutritional outcomes , and show no difference in complications between the two methods . It is not clear which feeding route provides the best nutritional outcomes . The primary purpose of this r and omized clinical pilot study was to compare the percentage of recommended calories and protein received by patients with neurological disease being fed enterally via gastric or duodenal feeding tubes . Secondary aims were to compare the following between groups : physiological effects of feeding , reasons for delay in feeding , volume of feeding residual , number of feeding tubes replaced , cost of feeding , and number and types of complications . A convenience sample of 25 neuro intensive care unit patients was r and omly assigned to gastric or duodenal feeding . Enteral feeding was ordered by using a st and ardized prescription formula and provided by the nursing staff . Serum albumin and prealbumin levels were measured at baseline , day 3 , and day 10 . Nitrogen balance was measured on day 10 . Enteral feeding data were collected daily . No significant differences were found between gastric and duodenal groups in nutritional outcomes , including percentage of recommended calories and protein received , physiological effects of feeding , reasons for delay in feeding , feeding residual , number of feeding tubes replaced , cost of feeding , and number and types of complications . Neither group achieved mean recommended caloric or protein intake during the 10 days of the study . Further research is needed to address how recommended nutrients can be provided enterally in a more timely and complete manner in critically ill NICU patients & NA ; This r and omized , controlled study employed two feeding protocol s for 107 participants in two intensive care units ( ICUs ) of a medical center to investigate the efficacy of intermittent nasogastric ( NG ) feeding in preventing aspiration pneumonia in critically ill patients on ventilators . The participants were r and omly assigned to receive continuous ( 51 patients ) or intermittent ( 56 patients ) feeding . The primary outcomes , including gastric emptiness index and pulmonary aspiration index , were examined on Day 0 and Day 7 of the intervention . In addition , patients were followed up to the 21st day to evaluate the secondary outcomes , which included length of stay ( LOS ) in the ICU and airway status . The results showed that the patients in the intermittent feeding group had a higher total intake volume at Day 7 ( p = .000 ) , had been extubated earlier at Day 21 ( p = .002 ) , and had a lower risk of aspiration pneumonia ( odds ratios : 0.146 , 95 % CI = 0.062 - 0.413 , p = .000 ) than the patients in the control group . Participants being treated with a high dose of dopamine were 2.95 times more likely to get aspiration pneumonia than those receiving a low dose of dopamine ( 95 % CI = 1.076 - 8.107 , p = .035 ) . However , there was no significant difference between the two groups ' LOS . The results of this study provide evidence that clinical caregivers may use to make better decisions in terms of feeding methods for critically ill patients Objective To evaluate the effect of intravenous erythromycin on gastric emptying and the success of enteral feeding in mechanically ventilated , critically ill patients with large volume gastric aspirates . Design Prospect i ve , double-blind , r and omized , and placebo-controlled trial . Setting General intensive care unit in a university hospital . Patients Twenty critically ill , mechanically ventilated patients intolerant of nasogastric feeding ( indicated by a residual gastric volume of ≥250 mL during feed administration at ≥40 mL/hr ) . Interventions After a gastric aspirate of ≥250 mL , which was discarded , the enteral feeding was continued at the previous rate for 3 hrs . Intravenous erythromycin ( 200 mg ) or placebo was then administered over 20 mins . The residual gastric contents were again aspirated and the volume was recorded 1 hr after the infusion began . Measurements and Main Results Gastric emptying was calculated as volume of feed infused into the stomach over 4 hrs minus the residual volume aspirated . Mean gastric emptying was 139 ± 37 ( ±sem ) mL after erythromycin and −2 ± 46 mL after placebo ( p = .027 ) . Nasogastric feeding was successful in nine of ten patients treated with erythromycin and five of ten who received placebo 1 hr after infusion ( chi-square p = .05 ) . Conclusion In critically ill patients who have large volumes of gastric aspirates indicating a failure to tolerate nasogastric feeding , a single small dose of intravenous erythromycin allows continuation of feed in the short term Objective To compare the effects of increasing the limit for gastric residual volume ( GRV ) in the adequacy of enteral nutrition . Frequency of gastrointestinal complications and outcome variables were secondary goals . Design An open , prospect i ve , r and omized study . Setting Twenty-eight intensive care units in Spain . Patients Three hundred twenty-nine intubated and mechanically ventilated adult patients with enteral nutrition ( EN ) . Interventions EN was administered by nasogastric tube . A protocol for management of EN-related gastrointestinal complications was used . Patients were r and omized to be included in a control ( GRV = 200 ml ) or in study group ( GRV = 500 ml ) . Measurements and results Diet volume ratio ( diet received/diet prescribed ) , incidence of gastrointestinal complications , ICU-acquired pneumonia , days on mechanical ventilation and ICU length of stay were the study variables . Gastrointestinal complications were higher in the control group ( 63.6 vs. 47.8 % , P = 0.004 ) , but the only difference was in the frequency of high GRV ( 42.4 vs. 26.8 % , P = 0.003 ) . The diet volume ratio was higher for the study group only during the 1st week ( 84.48 vs. 88.20 % ) ( P = 0.0002 ) . Volume ratio was similar for both groups in weeks 3 and 4 . Duration of mechanical ventilation , ICU length of stay or frequency of pneumonia were similar . Conclusions Diet volume ratio of mechanically ventilated patients treated with enteral nutrition is not affected by increasing the limit in GRV . A limit of 500 ml is not associated with adverse effects in gastrointestinal complications or in outcome variables . A value of 500 ml can be equally recommended as a normal limit for GRV A.S.P.E.N. and SCCM are both nonprofit organizations composed of multidisciplinary healthcare professionals . The mission of A.S.P.E.N. is to improve patient care by advancing the science and practice of clinical nutrition and metabolism . The mission of SCCM is to secure the highest quality care for all critically ill and injured patients . Guideline Limitations : These A.S.P.E.N.−SCCM Clinical Guidelines are based on general conclusions of health professionals who , in developing such guidelines , have balanced potential benefits to be derived from a particular mode of medical therapy against certain risks inherent with such therapy . However , practice guidelines are not intended as absolute requirements . The use of these practice guidelines does not in any way project or guarantee any specific benefit in outcome or survival . The judgment of the healthcare professional based on individual circumstances of the patient must always take precedence over the recommendations in these guidelines . The guidelines offer basic recommendations that are supported by review and analysis of the current literature , other national and international guidelines , and a blend of expert opinion and clinical practicality . The population of critically ill patients in an intensive care unit ( ICU ) is not homogeneous . Many of the studies on which the guidelines are based are limited by sample size , patient heterogeneity , variability in disease severity , lack of baseline nutritional status , and insufficient statistical power for analysis . Periodic Guideline Review and Up date : This particular report is an up date and expansion of guidelines published by A.S.P.E.N. and SCCM in 2009 ( 1 ) . Governing bodies of both A.S.P.E.N. and SCCM have m and ated that these guidelines be up date d every three to five years . The data base of r and omized controlled trials ( RCTs ) that served as the platform for the analysis of the literature was assembled in a joint “ harmonization process ” with the Canadian Clinical Guidelines group . Once completed , each group operated separately in their interpretation of the studies and derivation of guideline recommendations ( 2 ) . The current A.S.P.E.N. and SCCM guidelines included in this paper were derived from data obtained via literature search es by the authors through December 31 , 2013 . Although the committee was aware of l and mark studies published after this date , these data were not included in this manuscript . The process by which the literature was evaluated necessitated a common end date for the search review . Adding a last-minute l and mark trial would have introduced bias unless a formalized literature search was re-conducted for all sections of the manuscript . Target Patient Population for Guideline : The target of these guidelines is intended to be the adult ( ≥ 18 years ) critically ill patient expected to require a length of stay ( LOS ) greater than 2 or 3 days in a medical ICU ( MICU ) or surgical ICU ( SICU ) . The current guidelines were exp and ed to include a number of additional subsets of patients who met the above criteria , but were not included in the previous 2009 guidelines . Specific patient population s addressed by these exp and ed and up date d guidelines include organ failure ( pulmonary , renal , and liver ) , acute pancreatitis , surgical subsets ( trauma , traumatic brain injury [ TBI ] , open abdomen [ OA ] , and burns ) , sepsis , postoperative major surgery , chronic critically ill , and critically ill obese . These guidelines are directed toward generalized patient population s but , like any other management strategy in the ICU , nutrition therapy should be tailored to the individual patient . Target Audience : The intended use of these guidelines is for all healthcare providers involved in nutrition therapy of the critically ill , primarily physicians , nurses , dietitians , and pharmacists . Methodology : The authors compiled clinical questions reflecting key management issues in nutrition therapy . A committee of multidisciplinary experts in clinical nutrition composed of physicians , nurses , pharmacists , and dietitians was jointly convened by the two societies Malnutrition is well recognized as a potential cause of increased morbidity and mortality in surgical patients . Early postoperative enteral nutrition through a feeding jejunostomy has been shown to improve results in patients undergoing major resections for gastrointestinal malignancies , trauma , and perforation peritonitis . We conducted a prospect i ve study to assess the feasibility and short-term efficacy of early enteral feeding through a nasoenteric tube placed intraoperatively in patients with nontraumatic perforation peritonitis with malnutrition . One hundred patients with nontraumatic perforation peritonitis with malnutrition undergoing exploratory laparotomy were r and omly divided into a test group ( TG ) and a control group ( CG ) of 50 patients each . TG patients had a nasoenteric tube placed at the time of surgery and were started on an enteral feeding regime 24 hours postoperatively . Patients in CG were allowed to eat orally once they passed flatus . The differences between the two groups with respect to nutritional intake in terms of energy and protein , changes in nutritional status as assessed by anthropometric , biochemical , and hematological values , amount of nasogastric aspirate , return of bowel motility , and complication rates were analyzed . The nasoenteric feeding was well tolerated . Total calorie and protein intake in TG was significantly higher than in CG : 981 vs. 505 kcal ( p < 0.01 ) , protein 24 vs. 0 g on day 3 and 1498 vs. 846 kcal ( p < 0.01 ) , protein 44 vs. 23 g ( p < 0.01 ) on day 7 , respectively . There was reduction in the amount of nasogastric aspirate in TG compared with that in CG : 431 vs. 545 ml/24 h on day 2 and 301 vs. 440 ml/24 h on day 3 , respectively . There was much faster recovery of bowel motility in TG than in CG at 3.34 vs. 4.4 days ( p < 0.01 ) . Complications developed in 39 of 50 patients in TG and in 47 of 50 in CG . The major complications occurred in 6 patients in TG and 12 patients in CG ( p < 0.05 ) . Patients with perforation peritonitis with malnutrition are likely to develop large energy deficits postoperatively , result ing in higher incidence of infective complications . Early enteral feeding through a nasoenteric tube is well tolerated by these patients and helps to improve energy and protein intake , reduces the amount of nasogastric aspirate , reduces the duration of postoperative ileus , and reduces the risk of serious complications BACKGROUND Critically ill patients typically receive ∼60 % of estimated calorie requirements . OBJECTIVES We aim ed to determine whether the substitution of a 1.5-kcal/mL enteral nutrition solution for a 1.0-kcal/mL solution result ed in greater calorie delivery to critically ill patients and establish the feasibility of conducting a multicenter , double-blind , r and omized trial to evaluate the effect of an increased calorie delivery on clinical outcomes . DESIGN A prospect i ve , r and omized , double-blind , parallel-group , multicenter study was conducted in 5 Australian intensive care units . One hundred twelve mechanically ventilated patients expected to receive enteral nutrition for ≥2 d were r and omly assigned to receive 1.5 ( n = 57 ) or 1.0 ( n = 55 ) kcal/mL enteral nutrition solution at a rate of 1 mL/kg ideal body weight per hour for 10 d. Protein and fiber contents in the 2 solutions were equivalent . RESULTS The 2 groups had similar baseline characteristics ( 1.5 compared with 1.0 kcal/mL ) . The mean ( ±SD ) age was 56.4 ± 16.8 compared with 56.5 ± 16.1 y , 74 % compared with 75 % were men , and the Acute Physiology and Chronic Health Evaluation II score was 23 ± 9.1 compared with 22 ± 8.9 . The groups received similar volumes of enteral nutrition solution [ 1221 mL/d ( 95 % CI : 1120 , 1322 mL/d ) compared with 1259 mL/d ( 95 % CI : 1143 , 1374 mL/d ) ; P = 0.628 ] , which led to a 46 % increase in daily calories in the group given the 1.5-kcal/mL solution [ 1832 kcal/d ( 95 % CI : 1681 , 1984 kcal/d ) compared with 1259 kcal/d ( 95 % CI : 1143 , 1374 kcal/d ) ; P < 0.001 ] . The 1.5-kcal/mL solution was not associated with larger gastric residual volumes or diarrhea . In this feasibility study , there was a trend to a reduced 90-d mortality in patients given 1.5 kcal/mL [ 11 patients ( 20 % ) compared with 20 patients ( 37 % ) ; P = 0.057 ] . CONCLUSIONS The substitution of a 1.0- with a 1.5-kcal/mL enteral nutrition solution administered at the same rate result ed in a 46 % greater calorie delivery without adverse effects . The results support the conduct of a large-scale trial to evaluate the effect of increased calorie delivery on clinical ly important outcomes in the critically ill Objective To assess gastrointestinal function in critically ill patients receiving muscle relaxant and to test clinical tolerance to enteral nutrition . Design and setting Prospect i ve study in an intensive care unit . Patients 20 critically ill patients requiring sedation with muscle relaxant to obtain adequate mechanical ventilation . Measurements and results Patients were r and omly selected to receive infusions of opioid sedation during the first session ( session 1 ) and the same sedation with muscle relaxation ( cisatracurium ) during the second session ( session 2 ) . Gastric emptying was assessed by the paracetamol absorption technique . Following the paracetamol absorption 200 ml enteral feed was given , and the residual gastric volume was measured 1 and 2 h after feeding . The maximum plasma concentration ( Cmax ) was 14 mg/l ( range 5–26 ) when patients received sedation , and 12 mg/l ( range 5–30 ) when they received muscle relaxant . The target time for reaching the maximum plasma concentration ( Tmax ) was 30 min ( range 20–60 ) and 35 min ( range 20–60 ) , respectively , in sessions 1 and 2 . There was no significant difference between the two session as regards Tmax , Cmax , or AUC0–120 . The residual volumes were 110±65 ml ( H1 ) and 95±76 ml ( H2 ) during session 1 and 125±85 ml ( H1 ) and 105±90 ml ( H2 ) during session 2 . Conclusions Enteral feeding is one of the most effective methods of supporting nutritional needs in the critically ill patient . We conclude that in critically ill patients requiring sedation gastric emptying is not improved by neuromuscular blocking agent OBJECTIVE To determine the effect of early enhanced enteral nutrition ( EN ) on clinical outcome of head-injured patients . DESIGN Prospect i ve , r and omized , controlled trial . SETTING Tertiary neurosurgical and trauma center . PATIENTS Eighty-two patients suffering head injury and requiring mechanical ventilation . INTERVENTIONS Patients were r and omized to receive st and ard EN ( gradually increased from 15 mL/hr up to estimated energy and nitrogen requirements ) or enhanced EN ( started at a feeding rate that met estimated energy and nitrogen requirements ) from day 1 . Good neurologic outcome ( Glasgow Outcome Scale score of 4 or 5 ) was determined at 3 and 6 months after injury , and the incidence of infective and total complications was determined during the hospital stay up to 6 months . MEASUREMENTS AND MAIN RESULTS Disease severity assessed by best preintubation Glasgow Coma Scale score , pupillary responses , Injury Severity Score , Acute Physiology and Chronic Health Evaluation II score , computed tomographic scan categorization , and age was similar in both groups . Intervention patients had a higher percentage of energy ( p = .0008 ) and nitrogen ( p<.0001 ) requirements met by EN in the first week after injury . Neurologic outcome at 6 months was similar between groups , but there was a tendency for more intervention patients to have a good neurologic outcome at 3 months than control patients ( 61 % vs. 39 % , p = .08 ) . Fewer intervention patients had an infective complication ( 61 % vs. 85 % , p = .02 ) or more than one total complication ( 37 % vs. 61 % , p = .046 ) compared with control patients . Enhanced EN was associated with a reduction in the ratio of serum concentration of C-reactive protein to albumin up to day 6 after injury ( p = .004 ) . CONCLUSIONS Enhanced EN appears to accelerate neurologic recovery and reduces both the incidence of major complications and postinjury inflammatory responses Objective To compare the initial ( D7 ) calorie intake and tolerability of two early enteral nutrition protocol s in which the optimal flow rate was introduced either immediately or gradually . Design Open , prospect i ve , r and omized study . Setting Two medical-surgical intensive care units . Patients One hundred consecutive intubated and mechanically ventilated patients . Interventions Early enteral nutrition was started within 24 h following intubation , and the optimal flow rate ( 25 Kcal/kg day−1 ) was either introduced immediately or reached in increments . Flow rate of the nutritional solution was adapted to the residual gastric volume , measured every 8 h , and the use of prokinetic agents was encouraged . Vomiting , regurgitation , colectasia , and suspected aspiration were defined as serious adverse events requiring withdrawal of enteral nutrition . Measurements and results When introduced immediately at optimal flow rate , early enteral nutrition led to a significant improvement in actual calorie supply ( p < 0.0001 ) . Although high residual gastric volume ( > 300 ml ) was more frequent when optimal flow rate was introduced immediately ( p = 0.04 ) , frequency of serious adverse events necessitating withdrawal of enteral nutrition was similar in the two groups ( p = 0.64 ) . Conclusions When residual gastric volume is measured regularly and prokinetic agents are used , enteral nutrition can be started early and be introduced at optimal dose regimen , thereby providing better calorie intake . Serious adverse events required early enteral nutrition withdrawal in only 15 patients , with no difference in frequency between the groups A modular tube feeding recipe ( MTF ) was design ed to meet the unique nutritional needs of burn patients , applying principles previously documented in our burned guinea pig model . MTF , a high-protein , low-fat , linoleic acid-restricted formulation is enriched with omega-3 fatty acids , arginine , cysteine , histidine , vitamin A , zinc , and ascorbic acid . Fifty patients , 3 to 76 years of age with burns ranging from 10 to 89 % total body surface area were prospect ively r and omized into three groups which blindly compared MTF to two enteral regimens widely utilized in the nutritional support of burns . Age , percent total and third-degree burn , resting energy expenditure , and calorie and protein intake were similar in all groups . Data analysis demonstrated significant superiority of MTF in the reduction of wound infection ( p less than 0.03 ) and length of stay/percent burn ( p less than 0.02 ) . MTF was also associated with a decreased incidence of diarrhea , improved glucose tolerance , lower serum triglycerides , reduced total number of infectious episodes and trends toward improved preservation of muscle mass , although statistical significance was not achieved . Seventy percent of deaths occurred in the group supported with an inherently large dose of fat and linoleic acid . Combining these observations , it is believed that MTF is effective in modulating an improved response to burn injury Purpose To evaluate the efficacy of transpyloric feeding ( TPF ) compared with gastric feeding ( GF ) with regard to the incidence of ventilator-associated pneumonia in severe traumatic brain injury patients ( TBI ) . Design and setting Prospect i ve , open-label , r and omized study in an intensive care unit of a university hospital . Patients One hundred and four CHI adult patients admitted for TBI between April 2007 and December 2008 . Patients were included within the first 24 h after ICU admission and were followed until discharge or 30 days after admission . Intervention Patients were r and omized to TPF or GF groups . They received the same diet , with 25 kcal kg−1 day−1 of calculated energy requirements and a nitrogen intake of 0.2 g N kg−1 day−1 . Primary outcome was the incidence of early and ventilatory-associated pneumonia . Secondary outcomes were enteral nutrition-related gastrointestinal complications ( GIC ) , days on mechanical ventilation , length of ICU stay and hospital stay , and sequential organ failure assessment score ( SOFA ) . Results The TPF group had a lower incidence of pneumonia , OR 0.3 ( 95 % CI 0.1–0.7 , P = 0.01 ) . There were no significant differences in other nosocomial infections . The TPF group received higher amounts of diet compared to the GF group ( 92 vs. 84 % , P < 0.01 ) and had lesser incidence of increased gastric residuals , OR 0.2 ( 95 % CI 0.04–0.6 , P = 0.003 ) . Conclusions Enteral nutrition delivered through the transpyloric route reduces the incidence of overall and late pneumonia and improves nutritional efficacy in severe TBI patients INTRODUCTION Critically ill patients placed on enteral nutrition ( EN ) are usually underfed . A volume-based feeding ( VBF ) protocol design ed to adjust the infusion rate to make up for interruptions in delivery should provide a greater volume of EN than the more common fixed hourly rate-based feeding ( RBF ) method . METHODS This single-center , r and omized ( 3:1 ; VBF/RBF ) prospect i ve study evaluated critically ill patients on mechanical ventilation expected to receive EN for ≥ 3 days . Once goal rate was achieved , the r and omized feeding strategy was implemented . In the VBF group , physicians used a total goal volume of feeds to determine an hourly rate . For the RBF group , physicians determined a constant hourly rate of infusion to meet goal feeds . RESULTS Sixty-three patients were enrolled in the study with a mean age of 52.6 years ( 60 % male ) . Six patients were excluded after r and omization because of early extubation . The VBF group ( n = 37 ) received 92.9 % of goal caloric requirements with a mean caloric deficit of -776.0 kcal compared with the RBF group ( n = 20 ) , which received 80.9 % of goal calories ( P = .01 ) and a caloric deficit of -1933.8 kcal ( P = .01 ) . Uninterrupted EN was delivered for 51.7 % of all EN days in VFB patients compared with 54.5 % in RBF patients . On days when feeding was interrupted , VFB patients overall received a mean 77.6 % of goal calories ( while RBF patients received 61.5 % of goal calories , P = .001 ) . No vomiting , regurgitation , or feeding intolerance occurred due to VBF . CONCLUSIONS A VBF strategy is safe and improves delivery to better meet caloric requirements than the st and ard more commonly used rate-based strategy BACKGROUND Few trials have studied the influence of illness severity on clinical outcomes of different tube-feeding routes . Whether gastric or postpyloric feeding route is more beneficial to patients receiving enteral nutrition remains controversial . OBJECTIVE To test whether illness severity influences the efficacy of enteral feeding route on clinical outcomes in patients with critical illness . DESIGN A 2-year prospect i ve , r and omized , clinical study was conducted to assess the differences between the nasogastric ( NG ) and nasoduodenal ( ND ) tube feedings on clinical outcomes . PARTICIPANTS / SETTING One hundred one medical adult intensive care unit ( ICU ) patients requiring enteral nutrition were enrolled in this study . INTERVENTION Patients were r and omly assigned to the NG ( n=51 ) or ND ( n=50 ) feeding route during a 21-day study period . Illness severity was dichotomized as " less severe " and " more severe , " with the cutoff set at Acute Physiology and Chronic Health Evaluation II score of 20 . MAIN OUTCOME MEASURES Daily energy and protein intake , feeding complications ( eg , gastric retention/vomiting/diarrhea/gastrointestinal bleeding ) , length of ICU stay , hospital mortality , nitrogen balance , albumin , and prealbumin . STATISTICAL ANALYSES PERFORMED Two-tailed Student t tests and Mann-Whitney U tests were used to analyze significant differences between variables in the study groups . Multiple regression was used to assess the effects of illness severity and enteral feeding routes on clinical outcomes . RESULTS Among less severely ill patients , no differences existed between the NG and ND groups in daily energy and protein intake , feeding complications , length of ICU stay , and nitrogen balance . Among more severely ill patients , the NG group experienced lower energy and protein intake , more tube feeding complications , longer ICU stay , and poorer nitrogen balance than the ND group . CONCLUSIONS To optimize nutritional support and taking medical re sources into account , the gastric feeding route is recommended for less severely ill patients and the postpyloric feeding route for more severely ill patients Objective : This study aim ed to a ) compare the efficacy of metoclopramide and erythromycin in the treatment of feed intolerance in critical illness ; and b ) determine the effectiveness of “ rescue ” combination therapy in patients who fail monotherapy . Design : R and omized controlled trial . Setting : Level III mixed medical and surgical intensive care unit . Patients : Ninety mechanically ventilated , medical patients with feed-intolerance ( gastric residual volume ≥250 mL ) . Interventions : Patients received either metoclopramide 10 mg intravenously four times daily ( n = 45 ) or erythromycin 200 mg intravenously twice a day ( n = 45 ) in a double-blind , r and omized fashion . After the first dose , nasogastric feeding was commenced and 6-hourly nasogastric aspirates were performed . If a gastric residual volume ≥250 mL recurred on treatment , open-label , combination therapy was given . Patients were studied for 7 days . Successful feeding was defined as 6-hourly gastric residual volume < 250 mL with a feeding rate ≥40 mL/hr . Measurements and Main Results : Demographic data , blood glucose levels , and use of inotropes , opioids , and benzodiazepines were similar between the two groups . After 24 hrs of treatment , both monotherapies reduced the mean gastric residual volume ( metoclopramide , 830 ± 32 mL to 435 ± 30 mL , p < .0001 ; erythromycin , 798 ± 33 mL to 201 ± 19 mL , p < .0001 ) and improved the proportion of patients with successful feeding ( metoclopramide = 62 % and erythromycin = 87 % ) . Treatment with erythromycin was more effective than metoclopramide , but the effectiveness of both treatments declined rapidly over time . In patients who failed monotherapy , rescue combination therapy was highly effective ( day 1 = 92 % ) and maintained its effectiveness for the study duration ( day 6 = 67 % ) . High pretreatment gastric residual volume was associated with poor response to prokinetic therapy . Conclusions : In critical illness , erythromycin is more effective than metoclopramide in treating feed intolerance , but the rapid decline in effectiveness renders both treatments suboptimal . Rescue combination therapy is highly effective , and further study is required to examine its role as the first-line therapy OBJECTIVE Critically ill patients often develop large gastric residual volumes during nasogastric feeding as a result of poor gastroduodenal motility . Nasojejunal feeding may decrease the severity of this complication . The aim of this study was to determine whether nasojejunal feeding improved tolerance of enteral nutrition by reducing gastric residual volumes . DESIGN R and omized , prospect i ve , clinical study . SETTING Intensive care unit of a university-affiliated hospital . PATIENTS Seventy-three intensive care unit patients expected to require nutritional support for at least 3 days . INTERVENTIONS Patients were r and omized to receive enteral nutrition via a nasojejunal tube ( placed endoscopically ) ( 34 patients ) or a nasogastric tube ( 39 patients ) . A strict protocol was followed , which included regular gastric residual volume measurement ( in both groups ) , the use of predetermined criteria for intolerance , and an attempt at nasojejunal feeding for those nasogastrically fed patients who were intolerant of enteral nutrition . MEASUREMENTS AND MAIN RESULTS Endoscopic placement of nasojejunal tubes was successful in 98 % with no complications of insertion . Patients fed via a nasojejunal tube had 1 ) a reduced total gastric residual volume in both the first 24 ( 197 vs. 491 mL , p = .02 ) and 48 hrs ( 517 vs. 975 mL , p = .02 ) ; 2 ) a reduced incidence of a single gastric residual volume > 150 mL ( 32 % vs. 74 % , p = .001 ) ; and 3 ) a trend toward a reduced incidence of intolerance of enteral nutrition ( 13 % vs. 31 % , p = .09 ) . Only 13 % of those nasogastrically fed patients who were initially intolerant of enteral nutrition remained intolerant once fed via a nasojejunal tube , and only 1.4 % of all patients met criteria for commencement of parenteral nutrition . CONCLUSIONS Enteral nutrition delivered via a nasojejunal tube is associated with a significant reduction in gastric residual volume , a strong trend toward improved tolerance of enteral nutrition , and an extremely low requirement for parenteral nutrition BACKGROUND To evaluate the effect of enteral feeding protocol s on key indicators of enteral nutrition in the critical care setting . METHODS International , prospect i ve , observational , cohort studies conducted in 2007 and 2008 in 269 intensive care units ( ICUs ) in 28 countries were combined for the purpose s of this analysis . The study included 5497 consecutively enrolled , mechanically ventilated , adult patients who stayed in the ICU for at least 3 days . Sites recorded the presence or absence of a feeding protocol operational in their ICU . They provided selected nutritional data on enrolled patients from ICU admission to ICU discharge for a maximum of 12 days . Sites that used a feeding protocol were compared with those that did not . RESULTS On average , protocol ized sites used more enteral nutrition ( EN ) alone ( 70.4 % of patients vs 63.6 % , P = .0036 ) , started EN earlier ( 41.2 hours from admission to ICU vs 57.1 , P = .0003 ) , and used more motility agents in patients with high gastric residual volumes ( 64.3 % of patients vs 49.0 % , P = .0028 ) compared with sites that did not use a feeding protocol . Overall nutritional adequacy ( 61.2 % of patients ' caloric requirements vs 51.7 % , P = .0003 ) and adequacy from EN were higher in protocol ized sites compared with non protocol ized sites ( 45.4 % of requirements vs 34.7 % , P < .0001 ) . EN adequacy remained significantly higher after adjustment for pertinent patient and ICU level baseline characteristics . CONCLUSIONS The presence of an enteral feeding protocol is associated with significant improvements in nutrition practice compared with sites that do not use such a protocol Objectives : To determine the effect of the enhanced protein-energy provision via the enteral route feeding protocol , combined with a nursing educational intervention on nutritional intake , compared to usual care . Design : Prospect i ve , cluster r and omized trial . Setting : Eighteen ICUs from United States and Canada with low baseline nutritional adequacy . Patients : One thous and fifty-nine mechanically ventilated , critically ill patients . Interventions : A novel feeding protocol combined with a nursing educational intervention . Measurements and Main Results : The two primary efficacy outcomes were the proportion of the protein and energy prescriptions received by study patients via the enteral route over the first 12 days in the ICU . Safety outcomes were the prevalence of vomiting , witnessed aspiration , and ICU-acquired pneumonia . The proportion of prescribed protein and energy delivered by enteral nutrition was greater in the intervention sites compared to the control sites . Adjusted absolute mean difference between groups in the protein and energy increases were 14 % ( 95 % CI , 5–23 % ; p = 0.005 ) and 12 % ( 95 % CI , 5–20 % ; p = 0.004 ) , respectively . The intervention sites had a similar improvement in protein and calories when appropriate parenteral nutrition was added to enteral sources . Use of the enhanced protein-energy provision via the enteral route feeding protocol was associated with a decrease in the average time from ICU admission to start of enteral nutrition compared to the control group ( 40.7–29.7 hr vs 33.6–35.2 hr , p = 0.10 ) . Complication rates were no different between the two groups . Conclusions : In ICUs with low baseline nutritional adequacy , use of the enhanced protein-energy provision via the enteral route feeding protocol is safe and results in modest but statistically significant increases in protein and calorie intake Objective To determine whether adding erythromycin to a gastric feeding regimen could render it as effective in meeting nutritional needs as transpyloric feeding . Design R and omized , controlled study . Setting University hospital medical , surgical , and neurologic care intensive care units . Patients Critically ill patients , requiring a projected 96 hrs of enteral feeding , who had no specific indication for tube location ( gastric or transpyloric ) . Eighty patients were r and omized . Interventions Patients were r and omized to gastric feeding with erythromycin ( 200 mg iv ) given every 8 hrs or feeding through a transpylorically placed feeding tube . Goal rate and feeding advancement were determined by protocol . Measurements and Main Results During the 96-hr period , the gastric group received 74 % of their goal calories and the transpyloric group received 67 % . The only day on which gastric feedings were superior was the first study day , where the gastric group attained 55 % of their goal , compared with 44 % in the transpyloric group . This 1-day difference was the result of an initial failure of tube placement in some subjects . Exclusion of these patients did not change overall results . Nutritional indexes , length of stay in the intensive care unit , ventilator dependence , and survival were not different between the two groups . Conclusions Gastric feeding with erythromycin as a prokinetic is equivalent to transpyloric feeding in meeting the nutritional goals of the critically ill BACKGROUND Optimal nutrition for patients in the intensive care unit has been proposed to be the provision of energy as determined by indirect calorimetry and the provision of protein of at least 1.2 g/kg . METHODS Prospect i ve observational cohort study in a mixed medical-surgical intensive care unit in an academic hospital . In total , 886 consecutive mechanically ventilated patients were included . Nutrition was guided by indirect calorimetry and protein provision of at least 1.2 g/kg . Cumulative intakes were calculated for the period of mechanical ventilation . Cox regression was used to analyze the effect of protein + energy target achieved or energy target achieved versus neither target achieved on 28-day mortality , with adjustments for sex , age , body mass index , Acute Physiology and Chronic Health Evaluation II , diagnosis , and hyperglycemic index . RESULTS Patients ' mean age was 63 ± 16 years ; body mass index , 26 ± 6 ; and Acute Physiology and Chronic Health Evaluation II , 23 ± 8 . For neither target , energy target , and protein + energy target , energy intake was 75 % ± 15 % , 96 % ± 5 % , and 99 % ± 5 % of target , and protein intake was 72 % ± 20 % , 89 % ± 10 % , and 112 % ± 12 % of target , respectively . Hazard ratios ( 95 % confidence interval ) for energy target and protein + energy target were 0.83 ( 0.67 - 1.01 ) and 0.47 ( 0.31 - 0.73 ) for 28-day mortality . CONCLUSIONS Optimal nutritional therapy in mechanically ventilated , critically ill patients , defined as protein and energy targets reached , is associated with a decrease in 28-day mortality by 50 % , whereas only reaching energy targets is not associated with a reduction in mortality BACKGROUND Specific morbidity related to underfeeding and overfeeding necessitates the design of nutrition support regimens that provide calories equal to those required on the basis of energy expenditure . This prospect i ve multicenter trial was design ed to determine what percent of patients in long-term acute care facilities receive feeding appropriate to their needs and whether accuracy of feeding has an impact on patient clinical status . METHODS Patients on mechanical ventilation who were hospitalized at 32 Vencor Hospitals over a 9-week period and who were receiving only enteral nutrition by continuous infusion at a presumed goal rate were evaluated once by indirect calorimetry ( IC ) while on feeding . Caloric intake over the preceding 24 hours was determined by physician orders and by patient intake/output ( I/O ) record . Caloric requirements were defined by measured resting energy expenditure ( REE ) + 10 % for activity . Degree of metabolism was defined by the ratio : ( measured REE/Harris-Benedict predicted REE ) x 100 , and the degree of feeding by the ratio : ( calories provided/calories required ) x 100 . RESULTS IC was performed on 335 patients ( mean , 11.2 patients per center ; range , 1 to 32 ) , of which 72 were excluded for nonphysiological results or failure to achieve steady state , 21 for receiving parenteral nutrition , and 29 for not being on mechanical ventilation at time of testing . The 213 study patients were 58.7 % male with mean age 70.1 years ( range , 20 to 90 years ) . Measured REE was < 25 kcal/kg in 66.2 % of patients and 25 to 35 kcal/kg in 28.6 % . Barely half ( 48.4 % ) of this patient population was hypermetabolic . Based on physician orders , the majority of patients ( 58.2 % ) were overfed , receiving > 110 % of required calories , and 12.2 % were underfed , receiving < 90 % of requirements . Discrepancies based on I/O records , however , suggested that 36.1 % of patients received < 90 % of those calories ordered . By either basis , only about 25 % of patients received feeding within 10 % of required calories . The percent of patients being overfed varied between centers , ranging from 32.2 % to 92.8 % , and was not affected by years of facility IC experience or volume of IC studies per month . The pattern of caloric provision as measured by degree of feeding correlated inversely to degree of metabolism ( p < .0001 , R2 = .24 ) . Accuracy of feeding had an impact on ventilatory status , as degree of feeding correlated inversely with minute ventilation ( p = .001 , R2 = .05 ) . Degree of overfeeding also led to significant increases in azotemia ( p = .033 , R2 = .02 ) . Extrapolating study data over 1 year , reduction in excess volume of enteral formula would have result ed in a cost savings of up to $ 1.3 million for the Vencor system . CONCLUSIONS Because energy expenditure is difficult to predict on the basis of conventional equations , patients in long-term acute care facilities routinely are overfed and underfed , with only 25 % receiving calories within 10 % of required needs . Measuring a patient 's energy requirement at least once by IC is important , because the degree of metabolism predicts how easily a patient will be underfed or overfed . The amount of infused calories should be compared with caloric requirements measured by IC , because the accuracy or degree of underfeeding or overfeeding has an impact on ventilatory status and the likelihood for developing azotemia . Although physician practice or bias may reduce the optimal clinical effect , the use of IC to determine caloric requirements may result in significant cost savings BACKGROUND This study sought to compare 2 strategies for the administration of enteral feeding to mechanically ventilated medical patients . METHODS The prospect i ve , controlled , clinical trial was carried out in a medical intensive care unit ( 19 beds ) in a university-affiliated , urban teaching hospital . Between May 1999 and December 2000 , 150 patients were enrolled . Patients were scheduled to receive their estimated total daily enteral nutritional requirements on either day 1 ( early-feeding group ) or day 5 ( late-feeding group ) of mechanical ventilation . Patients in the late-feeding group were also scheduled to receive 20 % of their estimated daily enteral nutritional requirements during the first 4 days of mechanical ventilation . RESULTS Seventy-five ( 50 % ) consecutive eligible patients were entered into the early-feeding group and 75 ( 50 % ) patients were enrolled in the late-feeding group . During the 5 five days of mechanical ventilation , the total intake of calories ( 2370 + /- 2000 kcal versus 629 + /- 575 kcal ; p < .001 ) and protein ( 93.6 + /- 77.2 g versus 26.7 + /- 26.6 g ; p < .001 ) were statistically greater for patients in the early-feeding group . Patients in the early-feeding group had statistically greater incidences of ventilator-associated pneumonia ( 49.3 % versus 30.7 % ; p = .020 ) and diarrhea associated with Clostridium difficile infection ( 13.3 % versus 4.0 % ; p = .042 ) . The early-feeding group also had statistically longer intensive care unit ( 13.6 + /- 14.2 days versus 9.8 + /- 7.4 days ; p = .043 ) and hospital lengths of stay ( 22.9 + /- 19.7 days versus 16.7 + /- 12.5 days ; p = .023 ) compared with patients in the late-feeding group . No statistical difference in hospital mortality was observed between patients in the early-feeding and late-feeding groups ( 20.0 % versus 26.7 % ; p = .334 ) . CONCLUSIONS The administration of more aggressive early enteral nutrition to mechanically ventilated medical patients is associated with greater infectious complications and prolonged lengths of stay in the hospital . Clinicians must balance the potential for complications result ing from early enteral feeding with the expected benefits of such therapy BACKGROUND Optimal nutrition of critically ill patients is still a matter of debate . This pilot trial aim ed to compare the impact of normocaloric vs hypocaloric feeding in critically ill patients in the first 7 days in the intensive care unit ( ICU ) . The primary end point was the rate of nosocomial infections during the ICU stay . METHODS Critically ill patients requiring artificial nutrition for at least 72 hours were included within 24 hours of ICU admission and r and omized into a normocaloric group ( receiving 100 % of their daily energy expenditure ) and a hypocaloric group ( receiving 50 % of their daily energy expenditure ) . RESULTS One hundred patients were included ( 54 in the normocaloric group and 46 in the hypocaloric group ) . There were 66 male and 34 female patients with a mean age of 65.8 ± 11.6 years . The mean daily caloric supply was 19.7 ± 5.7 kcal/kg for the normocaloric group and 11.3 ± 3.1 kcal/kg for the hypocaloric group ( P = .0001 ) . Insulin dem and was significantly higher and gastrointestinal intolerance more frequent in the normocaloric group than in the hypocaloric group . Nosocomial infections were detected more frequently in the hypocaloric group than in the normocaloric group ( 26.1 % vs 11.1 % , respectively ) . The ICU mortality rate was 22.2 % in the normocaloric group and 21.7 % in the hypocaloric group ( not significant ) . The hospital mortality rate was 31.5 % in the normocaloric group and 37.0 % in the hypocaloric group ( P = .67 ) . CONCLUSION Hypocaloric feeding in the first 7 days in critically ill patients was associated with more nosocomial infections but less insulin dem and and less gastrointestinal intolerance compared with normocaloric feeding . TRIAL REGISTRATION NUMBER DRKS00000104 ( German Clinical Trials Register ) OBJECTIVE This study was conducted to develop evidence -based clinical practice guidelines for nutrition support ( ie , enteral and parenteral nutrition ) in mechanically ventilated critically ill adults . OPTIONS The following interventions were systematic ally review ed for inclusion in the guidelines : enteral nutrition ( EN ) versus parenteral nutrition ( PN ) , early versus late EN , dose of EN , composition of EN ( protein , carbohydrates , lipids , immune-enhancing additives ) , strategies to optimize delivery of EN and minimize risks ( ie , rate of advancement , checking residuals , use of bedside algorithms , motility agents , small bowel versus gastric feedings , elevation of the head of the bed , closed delivery systems , probiotics , bolus administration ) , enteral nutrition in combination with supplemental PN , use of PN versus st and ard care in patients with an intact gastrointestinal tract , dose of PN and composition of PN ( protein , carbohydrates , IV lipids , additives , vitamins , trace elements , immune enhancing substances ) , and the use of intensive insulin therapy . OUTCOMES The outcomes considered were mortality ( intensive care unit [ ICU ] , hospital , and long-term ) , length of stay ( ICU and hospital ) , quality of life , and specific complications . EVIDENCE We systematic ally search ed MEDLINE and CINAHL ( cumulative index to nursing and allied health ) , EMBASE , and the Cochrane Library for r and omized controlled trials and meta-analyses of r and omized controlled trials that evaluated any form of nutrition support in critically ill adults . We also search ed reference lists and personal files , considering all articles published or unpublished available by August 2002 . Each included study was critically appraised in duplicate using a st and ard scoring system . VALUES For each intervention , we considered the validity of the r and omized trials or meta-analyses , the effect size and its associated confidence intervals , the homogeneity of trial results , safety , feasibility , and the economic consequences . The context for discussion was mechanically ventilated patients in Canadian ICUs . BENEFITS , HARMS , AND COSTS The major potential benefit from implementing these guidelines is improved clinical outcomes of critically ill patients ( reduced mortality and ICU stay ) . Potential harms of implementing these guidelines include increased complications and costs related to the suggested interventions . SUMMARIES OF EVIDENCE AND RECOMMENDATIONS : When considering nutrition support in critically ill patients , we strongly recommend that EN be used in preference to PN . We recommend the use of a st and ard , polymeric enteral formula that is initiated within 24 to 48 hours after admission to ICU , that patients be cared for in the semirecumbent position , and that arginine-containing enteral products not be used . Strategies to optimize delivery of EN ( starting at the target rate , use of a feeding protocol using a higher threshold of gastric residuals volumes , use of motility agents , and use of small bowel feeding ) and minimize the risks of EN ( elevation of the head of the bed ) should be considered . Use of products with fish oils , borage oils , and antioxidants should be considered for patients with acute respiratory distress syndrome . A glutamine-enriched formula should be considered for patients with severe burns and trauma . When initiating EN , we strongly recommend that PN not be used in combination with EN . When PN is used , we recommend that it be supplemented with glutamine , where available . Strategies that maximize the benefit and minimize the risks of PN ( hypocaloric dose , withholding lipids , and the use of intensive insulin therapy to achieve tight glycemic control ) should be considered . There are insufficient data to generate recommendations in the following areas : use of indirect calorimetry ; optimal pH of EN ; supplementation with trace elements , antioxidants , or fiber ; optimal mix of fats and carbohydrates ; use of closed feeding systems ; continuous versus bolus feedings ; use of probiotics ; type of lipids ; and mode of lipid delivery . VALIDATION This guideline was peer- review ed and endorsed by official representatives of the Canadian Critical Care Society , Canadian Critical Care Trials Group , Dietitians of Canada , Canadian Association of Critical Care Nurses , and the Canadian Society for Clinical Nutrition . SPONSORS This guideline is a joint venture of the Canadian Critical Care Society , the Canadian Critical Trials Group , the Canadian Society for Clinical Nutrition , and Dietitians of Canada . The Canadian Critical Care Society and the Institute of Nutrition , Metabolism , and Diabetes of the Canadian Institutes of Health Research provided funding for development of this guideline OBJECTIVE To evaluate transpyloric feeds as they have been proposed as a means of providing enteric nutrition more rapidly and minimizing morbidity in ventilated trauma patients . METHODS Between July of 1994 and June of 1997 , 80 adult ventilated trauma patients were enrolled in a r and omized controlled trial of duodenal versus gastric feeds . Feeding was initiated within 72 hours of injury . RESULTS Forty-three patients received gastric feeds ( G ) , and 37 patients received duodenal feeds ( D ) . Mean age was 34.7+/-15.7 years ( G ) and 33.6+/-17.5 years ( D ) ; the difference in age was not significant ( NS ) . Mean Injury Severity Score was 30.0+/-11 ( G ) , 33.0+/-9.7 ( D ) , NS . Mean Acute Physiology and Chronic Health Evaluation ( APACHE II ) score was 18.0+/-6.0 ( G ) and 18.0+/-7.4 ( D ) , NS . Thirty-four of 43 patients were men ( G ) and 28 of 37 patients were men ( D ) , NS . Use of narcotics and paralytics between the two groups was not significantly different . Energy requirements were 1.4 times basal energy expenditure at 2,127+/-304 Kcal ( G ) and 2,089+/-274 Kcal ( D ) , NS . Intensive care unit length of stay was a median of 7 days ( range , 3 - 32 days ) ( G ) and 10 days ( range , 3 - 24 days ) ( D ) , NS . Number of days on ventilator was a median of 5 days ( range , 3 - 15 days ) ( G ) and 9 days ( range , 2 - 13 days ) ( D ) , NS . Hospital length of stay was a median of 25 days ( range , 9 - 88 days ) ( G ) and 30 days ( range , 16 - 47 days ) ( D ) , NS . Recorded morbidity was not significantly different . Pneumonia rates were 42 % ( G ) and 27 % ( D ) , NS . Time to tolerate full-strength feeds for 24 consecutive hours was 43.8 hours + /-22.6 ( G ) and 34.3 hours + /-7.1 ( D ) , difference significant at p = 0.02 . CONCLUSION Length of stay and ventilator days were not significantly different . A larger trial would be required to determine differences in the rates of pneumonia < 20 % . Transpyloric-duodenal feeds significantly reduce the time required to achieve targeted enteric nutrition Objective To compare the outcomes of intensive care unit patients fed through a nasogastric vs. a nasal – small-bowel tube including the time from tube placement to feeding , time to reach goal rate , and adverse events . Design Sixty patients were prospect ively r and omized to receive gastric or small-bowel tube feedings . Nursing staff attempted to place a feeding tube in the desired position , and placement was confirmed radiographically after each bedside attempt . After two unsuccessful attempts , the feeding tube was placed under fluoroscopy . Feedings were started at 30 mL/hr and advanced to the patient ’s specific goal rate . Setting Twenty-bed medical intensive care unit . Patients Sixty medical patients admitted/transferred to the intensive care unit . Interventions Tube feeds were held for 2 hrs if any residual was > 200 mL. Measurements Times were recorded at the initial tube insertion , onset of feeding , achievement of goal rate , and termination of feeding . Adverse outcomes included witnessed aspiration , vomiting , and clinical /radiographic evidence of aspiration . Patients were followed up for the duration of feeding , until leaving the intensive care unit , or for a maximum of 14 days . Main Results Patients fed in the stomach received nutrition sooner from initial placement attempt ( 11.2 hrs vs. 27.0 hrs ) and with fewer attempts ( one vs. two ) than those fed in the small bowel . Patients achieve goal rate sooner ( 28.8 hrs vs. 43.0 hrs ) with gastric feeding compared with small-bowel feeding . There was no difference in aspiration events . Conclusions Gastric feeding demonstrates no increase in aspiration or other adverse outcomes compared with small-bowel feeding in the intensive care unit . Gastric feeding can be started and advanced to goal sooner with fewer placement attempts than small-bowel feeding Objective To compare nutritional status , gastric colonization , and rates of nosocomial pneumonia in ICU patients r and omized to gastric tube feeding vs. patients fed by an endoscopically placed jejunal tube . Design R and omized , prospect i ve study . Setting Medical and surgical ICUs at Boston City Hospital ; surgical ICU at University Hospital . Patients Of the 38 study patients , 19 were r and omized to gastric tube feeding and 19 were r and omized to an endoscopically placed jejunal tube . The two groups were similar in age , sex , race , underlying disease , and type of surgery . Results The two patient groups were similar in number of days fed , duration of ICU stay , duration of mechanical ventilation , days of antibiotic therapy , and days with fever . Compared with the gastric group , the jejunal group had more patients with circulatory shock on admission ( 79 % vs. 68.4 % ) , higher admission Acute Physiology Score ( 24.0 vs. 21.7 ) , and fewer patients with pneumonia at r and omization ( 26.3 % vs. 31.6 % ) . The jejunal group received a significantly higher percentage of their daily goal caloric intake ( p = .05 ) , and had greater increases in serum prealbumin concentrations ( p < .05 ) than the patients with gastric tube feeding . Although the jejunal tube group had more days of diarrhea ( 3.3 ±PT 6.6 vs. 1.8 ±PT 2.9 ) , this difference was not statistically significant . Nosocomial pneumonia was diagnosed clinical ly in two ( 10.5 % ) patients in the gastric tube group and in no patients in the jejunal tube group . Conclusions Patients fed by jejunal tube received a significantly higher proportion of their daily goal caloric intake , had a significantly greater increase in serum prealbumin concentrations , and had a lower rate of pneumonia than patients fed by continuous gastric tube feeding OBJECTIVE To investigate the effect of cisapride , a relatively new prokinetic agent , on gastric emptying in critically ill patients . DESIGN Prospect i ve , r and omized , controlled study . SETTING Adult medical/surgical intensive care unit in a university hospital . PATIENTS Twenty-one consecutively enrolled patients , requiring prolonged mechanical ventilation and enteral feeding . INTERVENTIONS Patients were r and omized to receive either no cisapride or 10 mg of cisapride four times daily , which was added to a st and ard enteral nutrition feeding protocol . MEASUREMENTS AND MAIN RESULTS Gastric emptying was evaluated by daily measurements of gastric residue and on days 5 through 7 by bedside scintigraphy . Normal values for gastric clearance of a tracer-labeled test meal and for measurements obtained in the supine position were determined in ten healthy volunteers . The mean time at which 50 % of the technetium 99m-labeled test meal was eliminated from the stomach ( T 1/2 ) in this control group was 31 + /- 15 mins . In ten critically ill patients ( enteral nutrition group ) , gastric emptying was markedly delayed after 5 to 7 days of enteral feeding ( mean T 1/2 = 78 + /- 40 mins ; p < .002 as compared with the control group ) . In contrast , patients treated with cisapride ( cisapride group ) showed an accelerated gastric emptying ( mean T 1/2 = 18 + /- 7 mins ; p > .05 as compared with controls ; p < .005 as compared with enteral nutrition group ) . The mean gastric residue over a 1-wk period was also significantly lower in the cisapride group than in the enteral nutrition group ( 17.7 + /- 8.9 vs. 94.5 + /- 33.4 mL ; p < .001 ) . CONCLUSIONS The data indicate that gastric emptying in critically ill , se date d , and mechanically ventilated patients can be significantly improved by adding cisapride to a routine enteral feeding protocol CONTEXT The amount of enteral nutrition patients with acute lung injury need is unknown . OBJECTIVE To determine if initial lower-volume trophic enteral feeding would increase ventilator-free days and decrease gastrointestinal intolerances compared with initial full enteral feeding . DESIGN , SETTING , AND PARTICIPANTS The EDEN study , a r and omized , open-label , multicenter trial conducted from January 2 , 2008 , through April 12 , 2011 . Participants were 1000 adults within 48 hours of developing acute lung injury requiring mechanical ventilation whose physicians intended to start enteral nutrition at 44 hospitals in the National Heart , Lung , and Blood Institute ARDS Clinical Trials Network . INTERVENTIONS Participants were r and omized to receive either trophic or full enteral feeding for the first 6 days . After day 6 , the care of all patients who were still receiving mechanical ventilation was managed according to the full feeding protocol . MAIN OUTCOME MEASURES Ventilator-free days to study day 28 . RESULTS Baseline characteristics were similar between the trophic-feeding ( n = 508 ) and full-feeding ( n = 492 ) groups . The full-feeding group received more enteral calories for the first 6 days , about 1300 kcal/d compared with 400 kcal/d ( P < .001 ) . Initial trophic feeding did not increase the number of ventilator-free days ( 14.9 [ 95 % CI , 13.9 to 15.8 ] vs 15.0 [ 95 % CI , 14.1 to 15.9 ] ; difference , -0.1 [ 95 % CI , -1.4 to 1.2 ] ; P = .89 ) or reduce 60-day mortality ( 23.2 % [ 95 % CI , 19.6 % to 26.9 % ] vs 22.2 % [ 95 % CI , 18.5 % to 25.8 % ] ; difference , 1.0 % [ 95 % CI , -4.1 % to 6.3 % ] ; P = .77 ) compared with full feeding . There were no differences in infectious complications between the groups . Despite receiving more prokinetic agents , the full-feeding group experienced more vomiting ( 2.2 % vs 1.7 % of patient feeding days ; P = .05 ) , elevated gastric residual volumes ( 4.9 % vs 2.2 % of feeding days ; P < .001 ) , and constipation ( 3.1 % vs 2.1 % of feeding days ; P = .003 ) . Mean plasma glucose values and average hourly insulin administration were both higher in the full-feeding group over the first 6 days . CONCLUSION In patients with acute lung injury , compared with full enteral feeding , a strategy of initial trophic enteral feeding for up to 6 days did not improve ventilator-free days , 60-day mortality , or infectious complications but was associated with less gastrointestinal intolerance . TRIAL REGISTRATION clinical trials.gov Identifiers : NCT00609180 and NCT00883948 UNLABELLED Enteral nutrition ( EN ) for the critically ill and mechanically ventilated patients can be administered either via the continuous or bolus methods . However , there is insufficient evidence supporting which of these methods may have a lower risk of aspiration and gastrointestinal ( GI ) complications . This study was conducted in order to identify the incidence of aspiration and GI complications using continuous enteral nutrition ( CEN ) and bolus enteral nutrition ( BEN ) in critically ill patients at the Rafik Hariri University Hospital ( RHUH ) , Beirut , Lebanon . METHODS A pseudo-r and omised controlled trial was conducted on 30 critically ill mechanically ventilated patients receiving EN for more than 72 h. Patients were r and omly assigned into the following groups : an experimental group that received CEN and a control group that received BEN . Furthermore , patients ' health characteristics data as well as the incidence of aspiration and GI complications ( high gastric residual volume " HGRV " , vomiting , diarrhoea , and constipation ) were subsequently collected . RESULTS There were no statistically significant differences between the effects of CEN versus BEN groups on the occurrence of aspiration , HGRV , diarrhoea , or vomiting ( P>0.05 ) . However , constipation was significantly greater in patients receiving CEN ( 10 patients ( 66.7 % ) ) as compared with those receiving BEN ( 3 patients ( 20 % ) ) ( P=0.025 ) . CONCLUSION CEN versus BEN methods did not affect the incidence of aspiration , HGRV , vomiting or diarrhoea . However , the incidence of constipation was significantly greater in patients receiving CEN This study is a r and omized controlled trial aim ed at determining the effects of abdominal massage on high gastric residual volume seen in patients intermittently fed with enteral nutrition through a nasogastric tube . The study also investigated consequent abdominal distension and vomiting complications . The study was carried out in a university hospital between January and December 2009 . The sample included 40 intervention ( abdominal massage ) and 40 control subjects . Findings demonstrated that 2.5 % of the subjects in the massage group and 30.0 % of the subjects in the control group developed high gastric residual volume from enteral nutrition through a nasogastric tube . Abdominal circumference measurements of subjects on the first and last days demonstrated that 20 % of the subjects in the control group and only 2.5 % of the subjects in the massage group developed abdominal distension ( p = .044 ) . Vomiting was observed in 10 % of the control subjects ; no vomiting was observed in the intervention group . Findings suggest that nurses should apply abdominal massage to subjects receiving enteral feedings intermittently to prevent high gastric residual volume and abdominal distension Background : The therapeutic use of the antineoplastic drug cisplatin ( DDP ) in the elderly is limited by its nephrotoxic effects . The aim of this study was to examine the effect of short-term calorie restriction ( CR ) on DDP-induced nephrotoxicity in aged rats . Methods : A group of 25-month-old male Sprague-Dawley rats were divided into two groups : ad libitum ( AL ) and CR , which were fed 60 % of the food consumed by AL rats for 8 weeks . The two groups were each further r and omly divided into two subgroups : OAL control , OAL+DDP , OCR control , and OCR+DDP . A single dose of DDP ( 6 mg/kg ) was injected intraperitoneally . Functional and structural changes of the kidneys were evaluated quantitatively by biochemical , histopathological , and morphometric analyses . Results : At the end of the 8 weeks , rats in the OCR group lost 14.8 % more body mass than rats in the OAL group . Pretreatment with CR had several effects : ( 1 ) it reduced the levels of blood urea nitrogen and serum creatinine , ( 2 ) it reduced the magnitude of the renal tubular epithelial damage , and ( 3 ) it significantly reduced the incidence of activated caspase-3 and TUNEL-positive cells in kidneys injured by DDP . However , SIRT1 had the opposite trend after DDP application between the two groups . Conclusions : Short-term CR exhibits a renoprotective effect in experimental DDP-induced renal injury , the mechanism of which may involve CR antiapoptotic effects and promotion of SIRT1 |
1,280 | 24,115,131 | RESULTS There is no evidence in favor of 1 treatment modality when considering likelihood of local control or overall survival .
There is a suggestion that RT may be associated with less measureable perturbation of voice as compared to surgery , but no significant differences were seen in patient perception .
The likelihood of laryngeal preservation may be higher when surgery can be offered as initial treatment .
For patients with early ( T1 ) glottic cancer , treatment options include the equally effective endolaryngeal surgery , with or without laser , or radiation therapy . | BACKGROUND Treatment options for early glottic cancer include transoral microsurgery or radiotherapy ( RT ) .
There is continuing debate about which is the superior treatment . | Carcinoma of the larynx is the most common cancer affecting the head and neck region . In Northern Europe , early laryngeal cancer is almost universally treated by irradiation , but elsewhere it is treated by surgery . The main aim of this study was to determine whether there was any difference in survival between the two main therapeutic options . The secondary aim was to assess speech and voice quality in a small , r and omized sample of patients from each treatment group Cancer of the larynx is the most prevalent non-cutaneous malignancy of the head neck region and its treatment presents a threat to both natural speech and survival . This study examines the manner in which two separate specialties in the same and different geographic regions vary in their opinions about the treatment of glottic laryngeal cancer . The goal was to define options available to patients and to classify controversies about optimal treatment which might be resolved in clinical trials . Question naires depicting different presentations of glottic larynx cancer were mailed to 1649 otolaryngologists and radiation oncologists in North America , Europe and Australasia . Half the doctors were asked to describe their preferred treatment for a patient while the others were asked to imagine that they themselves were the patient . In all the disease situations opinions varied significantly with respect to the treatment modality advised ( whether to employ surgical or radiotherapy approaches ) and in more extensive disease situations the intention of treatment also varied depending on whether a curative approach should involve conservation or loss of the larynx . Doctors also recommended similar treatment for their patients as they would for themselves . Apart from disease extent the most significant variables influencing recommendations were the physicians ' specialty ( P = 0.0001 ) and where they practice ( P = 0.0001 ) . These findings demonstrate diversity of opinion which is influenced more profoundly by the traditions of the specialties and geographic location of practice than by the reported results of treatments for laryngeal cancer . Convictions about optimal management have become barriers to the assessment of the relative value of different treatments and to ensuring that patients are fully informed about management options . The profession should regard as a high priority efforts to resolve these therapeutic conflicts which are associated with major differences in quality of life Both radiotherapy and laser surgery give excellent results in the treatment of T1a glottic carcinoma . In this study , we compared the outcome of these treatment options . Demographic details and continuous follow-up with exact cause of death have been recorded prospect ively for 351 patients with T1a glottic carcinoma at a tertiary referral centre in two consecutive decennia 1986–2005 . Patients were treated with radiotherapy ( 163 patients ) until 1996 when laser surgery was adopted as primary treatment ( 188 patients ) . The minimum follow-up time was 29 months . Neither the estimated 5-year disease-free survival , the disease-specific survival nor the crude survival differ between the two treatment options . The incidence of mainly local recurrences was equal during the first 3 years , followed by an increase in number of recurrences in the laser-operated patients . The odds ratio for a laryngectomy was 13.5 in patients treated with radiotherapy ( P = 0.002 ) , but mortality due to recurrence did not differ between the groups . The incidence of second primaries was equal ( 11 % ) but death due to second primaries differed significantly , favouring laser-treated patients ( P = 0.003 ) . In conclusion , the relative risk for a laryngectomy when a tumour recurs is 12.7 times higher in patients primarily treated with irradiation for T1a laryngeal carcinoma , compared with patients treated with laser surgery . Regarding the treatment costs , treatment impact on patients and organ preservation , we consider laser therapy to be the better treatment option for patients with T1a glottic cancer as no difference in survival could be observed OBJECTIVE To compare the functional and oncologic outcomes of transoral CO₂ laser microsurgery relative to radiotherapy for early-stage glottic carcinoma . DESIGN Functional analysis : population -based , prospect i ve , nonr and omized consecutive series of stage 1 and 2 glottic carcinoma treated with laser surgery ( n = 54 ) or radiotherapy ( n = 25 ) . Oncologic analysis : population -based , historical cohort comparing laser surgery ( n = 54 ) and radiotherapy ( n = 76 ) . SETTING Academic cancer centre . METHODS AND OUTCOME MEASURES Functional results were prospect ively collected prior to treatment and at 3 , 6 , 12 , and 24 months following treatment using vali date d performance scales assessing general level of function , speech , and swallowing . Oncologic results were collected from a larger cohort from the cancer registry of CancerCare MB . RESULTS Laser surgery result ed in a voice that was less likely to be understood all the time ( Performance Status Scale for Head and Neck Cancer Patients : underst and ability score < 100 ; OR = 12.2 ; p = .03 ) and a higher likelihood of having a Voice H and icap Index ( VHI-10 ) score of 10 or more ( OR = 16.2 ; p = .001 ) . Five-year laryngectomy-free survival rates for laser versus radiation were 87 versus 76 % ( p = .16 ) . Subset analysis revealed that stage 1 5-year laryngeal preservation rates for laser ( n = 51 ) versus radiation ( n = 46 ) were 100 versus 86 % ( p = .02 ) . CONCLUSIONS There is a higher likelihood of hoarseness after laser surgery , but the severity of this h and icap is mild in most patients . Laser microsurgery results in excellent laryngeal preservation rates , which may exceed those of radiation In 1980 - 1987 , a cooperative r and omized study of 363 patients with stage III laryngeal cancer ( T1 - 3N0 - 1M0 ) was carried out . In 249 patients tumor was located in the vestibular space and in 114 in the vocal cord area ; 78.5 % of the patients had no regional metastases ( N0 ) and 21.5 % had metastases ( N1 ) . Combined therapy was applied to 251 patients , 135 of which were first exposed to radiotherapy and then to surgery and 116 were first exposed to surgery and then radiotherapy . In 71 patients , regional zones underwent preventive treatment ( in 24 patients elective radiotherapy and in 47 preventive removal of the cervical fat were used ) . In 112 patients , the therapeutic protocol was modified due to different reasons ( 69 patients underwent only surgery and 43 radical radiotherapy ) . The therapeutic results were assessed in terms of three parameters : incidence of relapses and regional metastases , relapse-free time , and survival . This approach revealed no significant differences in the efficacy of the different protocol s of the combined treatment . The 5-year survival rate of the patients with vestibular and cord space tumor was 77.9 % and 80.7 % respectively , when treated according to the radiotherapy + surgery protocol , and 82.8 % and 89.2 % , respectively , when treated according to the surgery + radiotherapy protocol . Comparison of preventive approaches showed that the 5-year survival rate increased by 92 % as a result of removal of the subcutaneous fat from the neck area Background : Transoral laser assisted microsurgical resection of early glottic laryngeal cancer is a relatively new treatment modality that is practised in many centres across the UK . In the absence of the results from r and omised clinical trials , clinicians may be guided by an expert panel consensus statement on transoral laser assisted microsurgical resection of early squamous cell cancer of the larynx |
1,281 | 28,375,430 | In general , modest positive effects were found but interventions were limited by a short follow-up duration . | Background Unhealthy lifestyle behaviors and childhood overweight are more common among children from families with a low socioeconomic position and ethnic minority children ( referred to as social disadvantaged children ) .
: This systematic review evaluates the effectiveness of interventions aim ed to improve lifestyle behaviours and /or prevent overweight among socially disadvantaged children in Europe . | OBJECTIVE . The study tested whether a combined environmental and educational intervention solely promoting water consumption was effective in preventing overweight among children in elementary school . METHODS . The participants in this r and omized , controlled cluster trial were second- and third- grade rs from 32 elementary schools in socially deprived areas of 2 German cities . Water fountains were installed and teachers presented 4 prepared classroom lessons in the intervention group schools ( N = 17 ) to promote water consumption . Control group schools ( N = 15 ) did not receive any intervention . The prevalence of overweight ( defined according to the International Obesity Task Force criteria ) , BMI SD scores , and beverage consumption ( in glasses per day ; 1 glass was defined as 200 mL ) self-reported in 24-hour recall question naires , were determined before ( baseline ) and after the intervention . In addition , the water flow of the fountains was measured during the intervention period of 1 school year ( August 2006 to June 2007 ) . RESULTS . Data on 2950 children ( intervention group : N = 1641 ; control group : N = 1309 ; age , mean ± SD : 8.3 ± 0.7 years ) were analyzed . After the intervention , the risk of overweight was reduced by 31 % in the intervention group , compared with the control group , with adjustment for baseline prevalence of overweight and clustering according to school . Changes in BMI SD scores did not differ between the intervention group and the control group . Water consumption after the intervention was 1.1 glasses per day greater in the intervention group . No intervention effect on juice and soft drink consumption was found . Daily water flow of the fountains indicated lasting use during the entire intervention period , but to varying extent . CONCLUSION . Our environmental and educational , school-based intervention proved to be effective in the prevention of overweight among children in elementary school , even in a population from socially deprived areas OBJECTIVE A multidimensional lifestyle intervention performed in 652 preschoolers ( 72 % of migrant , 38 % of low educational level ( EL ) parents ) reduced body fat , but not BMI and improved fitness . The objective of this study is to examine whether the intervention was equally effective in children of migrant and /or low EL parents . METHODS Cluster-r and omized controlled single blinded trial , conducted in 2008/09 in 40 r and omly selected preschools in Switzerl and . The culturally tailored intervention consisted of a physical activity program and lessons on nutrition , media use and sleep . Primary outcomes included BMI and aerobic fitness . Secondary outcomes included % body fat , waist circumference and motor agility . RESULTS Children of migrant parents benefitted similarly from the intervention compared to their counterparts ( p for interaction≥ 0.09 ) . However , children of low EL parents benefitted less , although these differences did not reach statistical significance ( p for interaction≥ 0.06 ) . Average intervention effect sizes for BMI were -0.10 , -0.05 , -0.11 and 0.04 kg/m(2 ) and for aerobic fitness were 0.55 , 0.20 , 0.37 and -0.05 stages for children of non-migrant , migrant , middle/high EL and low EL parents , respectively . CONCLUSIONS This intervention was similarly effective among preschoolers of migrant parents compared to their counterparts , while children of low EL parents benefitted less PURPOSE A positive outcome in self-reported behavior could be detected erroneously if an intervention caused over-reporting of the targeted behavior . Data collected from a multi-site r and omized trial were examined to determine if adolescent girls who received a physical activity intervention over-reported their activity more than girls who received no intervention . METHODS Activity was measured using accelerometers and self-reports ( 3-Day Physical Activity Recall , 3DPAR ) in cross-sectional sample s preintervention ( 6th grade , n = 1,464 ) and post-intervention ( 8th grade , n = 3,114 ) . Log-transformed accelerometer minutes were regressed on 3DPAR blocks , treatment group , and their interaction , while adjusting for race , body mass index , and timing of data collection . RESULTS Preintervention , the association between measures did not differ between groups , but post-intervention 3DPAR blocks were associated with fewer log-accelerometer minutes of moderate-vigorous physical activity ( MVPA ) in intervention girls than in control girls ( p = 0.002 ) . The group difference was primarily in the upper 15 % of the 3DPAR distribution , where control girls had > 1.7 more accelerometer minutes of MVPA than intervention girls who reported identical activity levels . Group differences in this sub sample were 8.5%-16.2 % of the mean activity levels ; the intervention was powered to detect a difference of 10 % . CONCLUSION Self-report measures should be interpreted with caution when used to evaluate a physical activity intervention Objective To test the effect of a multidimensional lifestyle intervention on aerobic fitness and adiposity in predominantly migrant preschool children . Design Cluster r and omised controlled single blinded trial ( Ballabeina study ) over one school year ; r and omisation was performed after stratification for linguistic region . Setting 40 preschool classes in areas with a high migrant population in the German and French speaking regions of Switzerl and . Participants 652 of the 727 preschool children had informed consent and were present for baseline measures ( mean age 5.1 years ( SD 0.7 ) , 72 % migrants of multicultural origins ) . No children withdrew , but 26 moved away . Intervention The multidimensional culturally tailored lifestyle intervention included a physical activity programme , lessons on nutrition , media use ( use of television and computers ) , and sleep and adaptation of the built environment of the preschool class . It lasted from August 2008 to June 2009 . Main outcome measures Primary outcomes were aerobic fitness ( 20 m shuttle run test ) and body mass index ( BMI ) . Secondary outcomes included motor agility , balance , percentage body fat , waist circumference , physical activity , eating habits , media use , sleep , psychological health , and cognitive abilities . Results Compared with controls , children in the intervention group had an increase in aerobic fitness at the end of the intervention ( adjusted mean difference : 0.32 stages ( 95 % confidence interval 0.07 to 0.57 ; P=0.01 ) but no difference in BMI ( −0.07 kg/m2 , −0.19 to 0.06 ; P=0.31 ) . Relative to controls , children in the intervention group had beneficial effects in motor agility ( −0.54 s , −0.90 to −0.17 ; P=0.004 ) , percentage body fat ( −1.1 % , −2.0 to −0.2 ; P=0.02 ) , and waist circumference ( −1.0 cm , −1.6 to −0.4 ; P=0.001 ) . There were also significant benefits in the intervention group in reported physical activity , media use , and eating habits , but not in the remaining secondary outcomes . Conclusions A multidimensional intervention increased aerobic fitness and reduced body fat but not BMI in predominantly migrant preschool children . Trial registration Clinical Trials NCT00674544 Background The prevalence of infant obesity is increasing , but there is a lack of evidence -based approaches to prevent obesity at this age . This study tested the acceptability and feasibility of evaluating a theory-based intervention aim ed at reducing risk of obesity in infants of overweight/obese women during and after pregnancy : the Healthy and Active Parenting Programme for Early Years ( HAPPY ) . Methods A feasibility r and omised controlled trial was conducted in Bradford , Engl and . One hundred twenty overweight/obese pregnant women ( Body Mass Index [ BMI ] ≥25 kg/m2 ) were recruited between 10–26 weeks gestation . Consenting women were r and omly allocated to HAPPY ( 6 antenatal , 6 postnatal sessions : N = 59 ) or usual care ( N = 61 ) . Appropriate outcome measures for a full trial were explored , including : infant ’s length and weight , woman ’s BMI , physical activity and dietary intake of the women and infants . Health economic data were collected . Measurement occurred before r and omisation and when the infant was aged 6 months and 12 months . Feasibility outcomes were : recruitment/attrition rates , and acceptability of : r and omisation , measurement , and intervention . Intra-class correlations for infant weight were calculated . Fidelity was assessed through observations and facilitator feedback . Focus groups and semi-structured interviews explored acceptability of methods , implementation , and intervention content . Results Recruitment targets were met ( ~20 women/month ) with a recruitment rate of 30 % of eligible women ( 120/396 ) . There was 30 % attrition at 12 months ; 66 % of recruited women failed to attend intervention sessions , but those who attended the first session were likely to continue to attend ( mean 9.4/12 sessions , range 1–12 ) . Reaction to intervention content was positive , and fidelity was high . Group clustering was minimal ; an adjusted effect size of −0.25 st and ard deviation scores for infant weight at 12 months ( 95 % CI : −0.16–0.65 ) favouring the intervention was observed using intention to treat analyses . No adverse events were reported . Conclusions The HAPPY intervention appeared feasible and acceptable to participants who attended and those delivering it , however attendance was low ; adaptations to increase initial attendance are recommended . Whilst the study was not powered to detect a definitive effect , our results suggest a potential to reduce risk of infant obesity . The evidence reported provides valuable lessons to inform progression to a definitive trial . Trial Registration Current Controlled Trials IS RCT Objective To assess feasibility and acceptability of a multifaceted , culturally appropriate intervention for preventing obesity in South Asian children , and to obtain data to inform sample size for a definitive trial . Design Phase II feasibility study of a complex intervention . Setting 8 primary schools in inner city Birmingham , UK , within population s that are predominantly South Asian . Participants 1090 children aged 6–8 years took part in the intervention . 571 ( 85.9 % from South Asian background ) underwent baseline measures . 85.5 % ( n=488 ) were followed up 2 years later . Interventions The 1-year intervention consisted of school-based and family-based activities , targeting dietary and physical activity behaviours . The intervention was modified and refined throughout the period of delivery . Main outcome measures Acceptability and feasibility of the intervention and of measurements required to assess outcomes in a definitive trial . The difference in body mass index ( BMI ) z-score between arms was used to inform sample size calculations for a definitive trial . Results Some intervention components ( increasing school physical activity opportunities , family cooking skills workshops , signposting of local leisure facilities and attending day event at a football club ) were feasible and acceptable . Other components were acceptable , but not feasible . Promoting walking groups was neither acceptable nor feasible . At follow-up , children in the intervention compared with the control group were less likely to be obese ( OR 0.41 ; 0.19 to 0.89 ) , and had lower adjusted BMI z-score ( −0.15 kg/m2 ; 95 % CI −0.27 to −0.03 ) . Conclusions The feasibility study informed components for an intervention programme . The favourable direction of outcome for weight status in the intervention group supports the need for a definitive trial . A cluster r and omised controlled trial is now underway to assess the clinical and cost-effectiveness of the intervention . Trial registration number IS RCT N51016370 OBJECTIVE To determine risk factors for consumption of soda and other sugar-sweetened beverages ( SSB ) among 2-year-old children . DESIGN The analysis was performed using three linked data sets : the 2004 - 2005 Oregon Pregnancy Risk Assessment Monitoring Survey ( PRAMS ) ; its longitudinal follow-up , 2006 - 2007 Oregon PRAMS-2 ; and 2004 - 2005 Oregon birth certificates . SETTING PRAMS is a surveillance programme supported by the federal Centers for Disease Control and Prevention and implemented by participating state health departments . Using mixed methods , PRAMS surveys women 2 - 6 months after a live birth . Oregon PRAMS-2 re-interviews respondents shortly after the index child 's second birthday . Oregon PRAMS over sample s minority women . SUBJECTS Using monthly cohorts , we r and omly selected 5851 women from the 2004 - 2005 birth certificates . In total 1911 women completed both PRAMS and PRAMS-2 . The weighted response rate of PRAMS-2 was 43.5 % . RESULTS Almost half of mothers ( 49.9 % ) reported that their child drank SSB on at least 1 d/week . Mothers whose children drank SSB at least once weekly were more likely to have low income ( adjusted OR=2.83 , 95 % CI 2.09 , 3.83 ) and to eat out on ≥2 d/week ( OR=2.11 % , 95 % CI 1.66 , 2.70 ) . Hispanic and non-Hispanic black women were most likely to report that their child drank SSB at least once weekly . CONCLUSIONS Half of mothers reported that their 2-year-old children drank SSB at least once weekly . Public health interventions and policies should address childhood SSB consumption including educating health-care providers and parents OBJECTIVES The purpose of this study was to evaluate the effect of a school-based intervention program to reduce overweight and improve fitness in primary school children . METHODS A cluster r and omized controlled design was used over one school year with schools as unit of r and omization . In total 20 schools and 2,622 children aged 6 - 12 years ( grade s 3 - 8 ) from multi-ethnic , low income inner-city neighbourhoods in Rotterdam , Netherl and s , participated . The intervention , named Lekker Fit ! ( Enjoy being fit ! ) was a multi-component intervention based on behavioural and ecological models . Main components of the intervention are the implementation of three physical education ( PE ) sessions a week by a professional PE teacher , additional sport and play activities outside school hours and an educational program . Main primary outcome measures were weight status , body mass index ( BMI ) , waist circumference and fitness ( 20 m shuttle run ) . RESULTS Significant positive intervention effects were found for percentage overweight children ( OR 0.53 ; 95 % CI 0.36 - 0.78 ) , waist circumference ( -1.29 cm ; 95 % CI -2.16 to -0.42 cm ) and 20 m shuttle run ( 0.57 laps ; 95 % CI 0.13 - 1.01 laps ) among pupils of grade s 3 - 5 ( 6 - 9-year olds ) . The prevalence of overweight in grade s 3 - 5 increased by 4.3 % in the control group and by 1.3 % in the intervention group . No significant effects were found for BMI or for grade s 6 - 8 ( 9 - 12-year olds ) . CONCLUSIONS Our results provide evidence for the effectiveness of the multi-component intervention Lekker Fit ! among pupils of grade s 3 - 5 and adds to the growing body of evidence that school-based programs with a focus on PA are most effective in reducing childhood obesity . [ IS RCT N84383524 ] Purpose The aim of the present study was to investigate the effect of the JUMP-in programme on sports participation , overall physical activity ( PA ) , shuttle run score and body composition in 6–12-year-old children . Methods JUMP-in is a school-based strategy combining environmental policy , neighbourhood , parents- and personal components . A controlled trial was carried out in 19 primary schools including 2848 children ( 50 % boys ) . Measures were performed at the beginning of the first school year ( T0 : 2006 ) and repeated at the end of the first ( T1 : 2007 ) and second school year ( T2 : 2008 ) . Results A significant beneficial intervention effect was found on organised sports participation ( OR 2.8 ( 2.2 to 3.6 ) ) . Effects were stronger for girls ( OR 3.6 ( 2.3 to 5.6 ) ) , and for Moroccan ( OR 4.2 ( 3.6 to 5.7 ) ) and Turkish children ( OR 3.2 ( 1.9 to 5.2 ) ) . Participation in organised sports was associated with increased shuttle run score . No significant intervention effects on overall daily PA rates and body composition were observed . Conclusion The present study proves that a school-based strategy combining environmental and personal interventions was successful in improving structural sports participation among children |
1,282 | 24,042,261 | Post-hoc analysis of r and omized controlled trials did not reveal any significant association between ADM and colorectal cancer risk .
Meta- analysis of published studies supports a protective association between metformin use and colorectal cancer risk in patients with diabetes mellitus . | BACKGROUND Antidiabetic medications ( ADM ) may modify colorectal cancer risk in patients with diabetes mellitus .
We performed a systematic review and meta- analysis , evaluating the effect of metformin , thiazolidinediones ( TZD ) , sulfonylureas , and insulin on colorectal cancer risk in diabetic patients . | Aims /hypothesisUsing the Echantillon Généraliste de Bénéficiaires : r and om 1/97 permanent sample of the French national healthcare insurance system data base ( EGB ) , we investigated whether , as previously suspected , the risk of cancer in insulin glargine ( A21Gly , B31Arg , B32Arg human insulin ) users is higher than in human insulin users . The investigation period was from 1 January 2003 to 30 June 2010 . Methods We used Cox proportional hazards time-dependent models that were stratified on propensity score quartiles for use of insulin glargine vs human insulin , and adjusted for insulin , biguanide and sulfonylurea possession rates to assess the risk of cancer or death in all or incident exclusive or predominant ( ≥80 % use time ) users of insulin glargine compared with equivalent human insulin users . Results Only type 2 diabetic patients were studied . Exposure rates varied from 2,273 and 614 patient-years for incident exclusive users of insulin glargine or human insulin , respectively , to 3125 and 2341 patient-years for all patients predominantly using insulin glargine or human insulin , respectively . All-type cancer HRs with insulin glargine vs human insulin ranged from 0.59 ( 95 % CI 0.28 , 1.25 ) in incident exclusive users to 0.58 ( 95 % CI 0.34 , 1.01 ) in all predominant users . Cancer risk increased with exposure to insulin or sulfonylureas in these patients . Adjusted HRs for death or cancer associated with insulin glargine compared with human insulin ranged from 0.58 ( 95 % CI 0.32 , 1.06 ) to 0.56 ( 95 % CI 0.36 , 0.87 ) . Conclusions /interpretationThere was no excess risk of cancer in type 2 diabetic patients on insulin glargine alone compared with those on human insulin alone . The overall risk of death or cancer in patients on insulin glargine was about half that of patients on human insulin , thereby excluding a competitive risk bias Aims /hypothesisObservational and mechanistic studies have suggested a possible relationship between treatment with metformin and decreased incidence of cancer in participants with type 2 diabetes . We extracted data for malignancies from the ADOPT ( A Diabetes Outcome Progression Trial ) and RECORD ( Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycaemia in Diabetes ) r and omised controlled clinical trials , in which the efficacy and /or safety of metformin was assessed in comparison with sulfonylureas and rosiglitazone . Methods Neoplasm occurrences were collected as adverse events in these studies . We review ed and re-analysed the individual participant data in both studies for serious adverse events , malignancies reported as adverse events and related neoplasms of special interest . Results In ADOPT , 50 participants ( 3.4 % ) on metformin and 55 ( 3.8 % ) on each of rosiglitazone and glibenclamide ( known as glyburide in the USA and Canada ) developed serious adverse event malignancies ( excluding non-melanoma skin cancers ) . This corresponds to 1.03 , 1.12 and 1.31 per 100 person-years , giving hazard ratios for metformin of 0.92 ( 95 % CI 0.63–1.35 ) vs rosiglitazone and 0.78 ( 0.53–1.14 ) vs glibenclamide . In RECORD , on a background of sulfonylurea , 69 ( 6.1 % ) participants developed malignant neoplasms in the metformin group , compared with 56 ( 5.1 % ) in the rosiglitazone group ( HR 1.22 [ 0.86–1.74 ] ) . On a background of metformin , 74 ( 6.7 % ) participants in the sulfonylurea group developed malignant neoplasms , compared with 57 ( 5.1 % ) in the rosiglitazone group ( HR 1.33 [ 0.94–1.88 ] ) . Conclusions /interpretationThe malignancy rates in these two r and omised controlled clinical trials do not support a view that metformin offers any particular protection against malignancy compared with rosiglitazone . However , they do not refute the possibility of a difference compared with sulfonylureas BACKGROUND The provision of sufficient basal insulin to normalize fasting plasma glucose levels may reduce cardiovascular events , but such a possibility has not been formally tested . METHODS We r and omly assigned 12,537 people ( mean age , 63.5 years ) with cardiovascular risk factors plus impaired fasting glucose , impaired glucose tolerance , or type 2 diabetes to receive insulin glargine ( with a target fasting blood glucose level of ≤95 mg per deciliter [ 5.3 mmol per liter ] ) or st and ard care and to receive n-3 fatty acids or placebo with the use of a 2-by-2 factorial design . The results of the comparison between insulin glargine and st and ard care are reported here . The co primary outcomes were nonfatal myocardial infa rct ion , nonfatal stroke , or death from cardiovascular causes and these events plus revascularization or hospitalization for heart failure . Microvascular outcomes , incident diabetes , hypoglycemia , weight , and cancers were also compared between groups . RESULTS The median follow-up was 6.2 years ( interquartile range , 5.8 to 6.7 ) . Rates of incident cardiovascular outcomes were similar in the insulin-glargine and st and ard-care groups : 2.94 and 2.85 per 100 person-years , respectively , for the first co primary outcome ( hazard ratio , 1.02 ; 95 % confidence interval [ CI ] , 0.94 to 1.11 ; P=0.63 ) and 5.52 and 5.28 per 100 person-years , respectively , for the second co primary outcome ( hazard ratio , 1.04 ; 95 % CI , 0.97 to 1.11 ; P=0.27 ) . New diabetes was diagnosed approximately 3 months after therapy was stopped among 30 % versus 35 % of 1456 participants without baseline diabetes ( odds ratio , 0.80 ; 95 % CI , 0.64 to 1.00 ; P=0.05 ) . Rates of severe hypoglycemia were 1.00 versus 0.31 per 100 person-years . Median weight increased by 1.6 kg in the insulin-glargine group and fell by 0.5 kg in the st and ard-care group . There was no significant difference in cancers ( hazard ratio , 1.00 ; 95 % CI , 0.88 to 1.13 ; P=0.97 ) . CONCLUSIONS When used to target normal fasting plasma glucose levels for more than 6 years , insulin glargine had a neutral effect on cardiovascular outcomes and cancers . Although it reduced new-onset diabetes , insulin glargine also increased hypoglycemia and modestly increased weight . ( Funded by Sanofi ; ORIGIN Clinical Trials.gov number , NCT00069784 . ) OBJECTIVE The antidiabetic properties of metformin are mediated through its ability to activate the AMP-activated protein kinase ( AMPK ) . Activation of AMPK can suppress tumor formation and inhibit cell growth in addition to lowering blood glucose levels . We tested the hypothesis that metformin reduces the risk of cancer in people with type 2 diabetes . RESEARCH DESIGN AND METHODS In an observational cohort study using record-linkage data bases and based in Tayside , Scotl and , U.K. , we identified people with type 2 diabetes who were new users of metformin in 1994–2003 . We also identified a set of diabetic comparators , individually matched to the metformin users by year of diabetes diagnosis , who had never used metformin . In a survival analysis we calculated hazard ratios for diagnosis of cancer , adjusted for baseline characteristics of the two groups using Cox regression . RESULTS Cancer was diagnosed among 7.3 % of 4,085 metformin users compared with 11.6 % of 4,085 comparators , with median times to cancer of 3.5 and 2.6 years , respectively ( P < 0.001 ) . The unadjusted hazard ratio ( 95 % CI ) for cancer was 0.46 ( 0.40–0.53 ) . After adjusting for sex , age , BMI , A1C , deprivation , smoking , and other drug use , there was still a significantly reduced risk of cancer associated with metformin : 0.63 ( 0.53–0.75 ) . CONCLUSIONS These results suggest that metformin use may be associated with a reduced risk of cancer . A r and omized trial is needed to assess whether metformin is protective in a population at high risk for cancer BACKGROUND & AIMS Hyperinsulinemia is a putative colorectal cancer ( CRC ) risk factor . Insulin resistance ( IR ) commonly precedes hyperinsulinemia and can be quantitatively measured by using the homeostasis model assessment -insulin resistance ( HOMA-IR ) index . To date , few studies have directly examined serum insulin as an indicator of CRC risk , and none have reported associations on the basis of HOMA-IR . METHODS We performed a case-cohort study within the Alpha-Tocopherol , Beta-Carotene Cancer Prevention ( ATBC ) Study ( n=29,133 ) . Baseline exposure and fasting serum biomarker data were available for 134 incident CRC case and 399 non-case subjects . HOMA-IR was derived as fasting insulin x fasting glucose/22.5 . Hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) were estimated by using age-adjusted and multivariable-adjusted Cox proportional hazards regression models . RESULTS Median ( interquartile range ) values for serum insulin , glucose , and HOMA-IR were 4.1 ( 2.9 - 7.2 ) mIU/L , 101 ( 94 - 108 ) mg/dL , and 0.99 ( 0.69 - 1.98 ) for case subjects and 4.1 ( 2.7 - 6.1 ) mIU/L , 99 ( 93 - 107 ) mg/dL , and 1.02 ( 0.69 - 1.53 ) for non-case subjects , respectively . On the basis of comparison of the highest versus lowest quartiles for each biomarker , insulin ( HR , 1.84 ; 95 % CI , 1.03 - 3.30 ) and HOMA-IR ( HR , 1.85 ; 95 % CI , 1.06 - 3.24 ) were significantly associated with incident CRC , whereas glucose was marginally associated with incident CRC ( HR , 1.70 ; 95 % CI , 0.92 - 3.13 ) in age-adjusted risk models . However , trends across biomarker quartiles were somewhat inconsistent ( P trend=.12 , .04 , and .12 , respectively ) , and multivariable adjustment generally attenuated the observed risk estimates . CONCLUSIONS Data from this prospect i ve study of male smokers provide limited support for hyperinsulinemia , hyperglycemia , and /or insulin resistance as CRC risk factors OBJECTIVE Controversy remains regarding the association between type 2 diabetes mellitus ( DM ) and colorectal cancer ( CRC ) risk . To clarify and extend the existing data , we prospect ively evaluated the association between self-reported type 2 DM ( onset at > 30 years of age ) and incident CRC , overall and by anatomic subsite , among postmenopausal women in the Iowa Women 's Health Study ( n = 35,230 ) . METHODS After 14 years of follow-up , a total of 870 incident CRC cases were identified through annual linkage to the Iowa Cancer Registry . DM was analyzed as reported at baseline and as a time-dependent variable using information obtained during follow-up . CRC risks were estimated using Cox proportional hazards regression models . RESULTS After adjusting for age , body mass index and other potential confounding variables , the relative risk ( RR ) for women with DM versus women without DM was modestly increased at 1.4 [ 95 % confidence interval ( 95 % CI ) , 1.1 - 1.8 ] . By anatomic subsite , the RR for proximal colon cancer was statistically significantly increased ( RR , 1.9 ; 95 % CI , 1.3 - 2.6 ) , whereas the RRs for distal colon ( RR , 1.1 ; 95 % CI , 0.6 - 1.8 ) and rectal cancer ( RR , 0.8 ; 95 % CI , 0.4 - 1.6 ) were not statistically different from unity . Analyses that included DM ascertained at baseline and follow-up yielded similar results . CONCLUSION In this large , prospect i ve study of postmenopausal women , the association between DM and incident CRC was found to be subsite specific . If confirmed by others , this finding implies that CRC prevention strategies among type 2 DM patients should include examination of the proximal colon Abstract Aims /hypothesis . To further investigate the association of cancer occurrence with the use of insulin glargine . Methods . We followed 114 838 individuals using insulin between 1 July and 31 December 2005 . From 1 January 2006 to 31 December 2008 , we noted the occurrence of malignancies ( cohort I ) . Insulin users between 1 July and 31 December 2006 were followed for the occurrence of malignancies in 2007 and 2008 ( cohort II ) . Users of insulin during three consecutive six-month periods from 1 July 2005 to 31 December 2006 were followed for the occurrence of malignancies in 2007 and 2008 ( cohort III ) . The Prescribed Drug Register , the Cancer Register , and the Causes of Death Register were used to obtain information on targeted person-time and outcome . We retrieved variables reflecting potential confounding factors from the Swedish National Diabetes Register , the Prescribed Drug Register , the Patient Register , the Medical Birth Register and the National Education Register . With Poisson regression we evaluated the association between insulin use and malignancy outcome with adjustment for confounders . Results . The adjusted incidence rate ratio ( and 95 % confidence interval ) for women who used insulin glargine alone compared with those who used other types of insulin , was 1.60 ( 1.10–2.32 ) for breast cancer but included 1.0 for malignancy outcomes other than breast cancer for men and women when analyzing cohort I with follow-up in 2006–2008 . For cohort II and III the corresponding incidence rate ratios were 1.38 ( 0.87–2.18 ) , and 0.87 ( 0.41–1.85 ) , respectively . Conclusion /interpretation . We do not see an increased risk during 2008 for breast cancer in the insulin glargine group . We need data for additional years before we can state with reasonable certainty that the increase in breast cancer incidence that we observed in Sweden in 2006 and 2007 was due to a r and om fluctuation or whether there is an association with the use of insulin glargine 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 Colorectal cancer is one of the major neoplasms and a leading cause of cancer death worldwide , and new preventive strategies are needed to lower the burden of this disease . Metformin , a biguanide , which is widely used for treating diabetes mellitus , has recently been suggestive to have a suppressive effect on tumorigenesis and cancer cell growth . In a previous study conducted in non-diabetic subjects , we showed that oral short-term low-dose metformin suppressed the development of colorectal aberrant crypt foci ( ACF ) . ACF have been considered as a useful surrogate biomarker of CRC , although the biological significance of these lesions remains controversial . We devised a prospect i ve r and omized controlled trial to evaluate the chemopreventive effect of metformin against metachronous colorectal polyps and the safety of this drug in non-diabetic post-polypectomy patients . Methods / Design This study is a multi-center , double-blind , placebo-controlled , r and omized controlled trial to be conducted in non-diabetic patients with a recent history of undergoing colorectal polypectomy . All adult patients visiting the Yokohama City University hospital or affiliated hospitals for polypectomy shall be recruited for the study . Eligible patients will then be allocated r and omly into either one of two groups : the metformin group and the placebo group . Patients in the metformin group shall receive oral metformin at 250 mg per day , and those in the placebo group shall receive an oral placebo tablet . At the end of 1 year of administration of metformin/placebo , colonoscopy will be performed to evaluate the polyp formation . Discussion This is the first study proposed to explore the effect of metformin against colorectal polyp formation . Metformin activates AMPK , which inhibits the mammalian target of rapamycin ( mTOR ) pathway . The mTOR pathway plays an important role in the cellular protein translational machinery and cell proliferation . Patients with type 2 diabetes taking under treatment with metformin have been reported to be at a lower risk of cancer development than those not taking under treatment with metformin . We showed in a previous study that metformin suppressed the formation of human colorectal ACF . We therefore decided to conduct a study to determine whether metformin might suppress the formation of human colorectal polyps . Trial registration This trial has been registered in the University hospital Medical Information Network ( UMIN ) Clinical Trials Registry as The biguanide metformin is widely used for treating diabetes mellitus . We previously showed the chemopreventive effect of metformin in two rodent models of colorectal carcinogenesis . However , besides epidemiologic studies , little is known about the effects of metformin on human colorectal carcinogenesis . The objective of this pilot study was to evaluate the chemopreventive effect of metformin on rectal aberrant crypt foci ( ACF ) , which are an endoscopic surrogate marker of colorectal cancer . We prospect ively r and omized 26 nondiabetic patients with ACF to treatment with metformin ( 250 mg/d , n = 12 ) or no treatment ( control , n = 14 ) ; 23 patients were evaluable for end point analyses ( 9 metformin and 14 control ) ; the two groups were similar in ACF number and other baseline clinical characteristics . Magnifying colonoscopy determined the number of rectal ACF in each patient at baseline and after 1 month in a blinded fashion ( as were all laboratory end point analyses ) . We also examined proliferative activity in colonic epithelium ( via proliferating cell nuclear antigen labeling index ) and apoptotic activity ( via terminal deoxynucleotidyl transferase dUTP nick-end labeling ) . At 1 month , the metformin group had a significant decrease in the mean number of ACF per patient ( 8.78 ± 6.45 before treatment versus 5.11 ± 4.99 at 1 month , P = 0.007 ) , whereas the mean ACF number did not change significantly in the control group ( 7.23 ± 6.65 versus 7.56 ± 6.75 , P = 0.609 ) . The proliferating cell nuclear antigen index was significantly decreased and the apoptotic cell index remained unaltered in normal rectal epithelium in metformin patients . This first reported trial of metformin for inhibiting colorectal carcinogenesis in humans provides preliminary evidence that metformin suppresses colonic epithelial proliferation and rectal ACF formation in humans , suggesting its promise for the chemoprevention of colorectal cancer . Cancer Prev Res ; 3(9 ) ; 1077–83 . © 2010 AACR BACKGROUND The remarkable similarity of lifestyle and environmental risk factors for type 2 ( non-insulin-dependent ) diabetes mellitus and colon cancer has led to the hypothesis that diabetes may increase the risk of this cancer . We prospect ively examined the relationship between diabetes and risk of colorectal cancer in a cohort of 118403 women aged 30 through 55 years who were without previously diagnosed cancer at baseline in 1976 . METHODS The women , who were enrolled in the Nurses ' Health Study , were assessed for history of diabetes at baseline and during follow-up by use of biennial question naires . Self-reported diabetes was vali date d by information obtained from a supplemental question naire on symptoms and treatment and was confirmed by medical record review in a sample of the participants . Incident cases of colorectal cancer were ascertained through medical record review . All reported P values are two-sided . RESULTS During 18 years of follow-up ( 201061 person-years ) , we documented 892 new cases of colorectal cancer . After adjustment for age , body mass index ( weight in kg/height in m2 ) , physical activity , and other covariates , relative risks ( RRs ) were 1.43 ( 95 % confidence interval [ CI ] = 1.10 - 1.87 ; P = .009 ) for colorectal cancer , 1.49 ( 95 % CI = 1.09 - 2.06 ; P = .01 ) for colon cancer , 1.11 ( 95 % CI = 0.56 - 2.21 ; P = .76 ) for rectal cancer , 1.56 ( 95 % CI = 1.07 - 2.28 ; P = .02 ) for advanced colorectal cancer , and 2.39 ( 95 % CI = 1.46 - 3.92 ; P = .0005 ) for fatal colorectal cancer . CONCLUSION Our data provide support for the hypothesis that diabetes is associated with an increased risk of colorectal cancer in women Aims /hypothesisType 2 diabetes has been associated with an increased risk of cancer . This study examines the effect of more vs less intensive glucose control on the risk of cancer in patients with type 2 diabetes . Methods All 11,140 participants from the Action in Diabetes and Vascular Disease : Preterax and Diamicron-MR Controlled Evaluation ( ADVANCE ) trial ( Clinical Trials.gov NCT00145925 ) were studied . Cancer incidence and cancer mortality was compared in groups r and omised to intensive or st and ard glucose control . Information on events during follow-up was obtained from serious adverse event reports and death certificates . HRs ( 95 % CI ) were calculated for all cancers , all solid cancers , cancer deaths and site-specific cancers . Results After a median follow-up of 5 years , 363 and 337 cancer events were reported in the intensive and st and ard control groups , respectively ( incidence 1.39/100 person-years [ PY ] and 1.28/100 PY ; HR 1.08 [ 95 % CI 0.93–1.26 ] ) . The incidences of all solid cancers and cancer deaths were 1.25/100 PY and 0.15/100 PY in the intensive group and 1.15/100 PY and 0.13/100 PY in the st and ard group ( HR 1.09 [ 95 % CI 0.93–1.27 ] for solid cancers , and 1.17 [ 0.75–1.84 ] for cancer death ) . Across all the major organ systems studied , no significant differences in the cancer incidences were observed in the intensive and st and ard control groups . Conclusions /interpretationsMore intensive glucose control achieved with a regimen that included greater use of gliclazide , insulin , metformin and other agents , did not affect the risk of cancer events or death in patients with type 2 diabetes 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 BACKGROUND & AIMS Type 2 diabetes mellitus ( DM ) is associated with an increased risk of colorectal cancer ( CRC ) ; it is not clear if this association varies by sex or other factors . Insulin use might also be associated with CRC risk . We investigated associations of type 2 DM and insulin use with CRC risk . METHODS The Cancer Prevention Study II Nutrition Cohort is a prospect i ve study of cancer incidence . In 1992 or 1993 , adult participants ( n = 184,194 ) completed a detailed , self-administered question naire . Follow-up question naires were sent in 1997 and every 2 years thereafter . Cox proportional hazards regression analysis was used to calculate relative risks ( RR ) and 95 % confidence intervals ( CI ) , adjusting for covariates . RESULTS After exclusions , 73,312 men and 81,663 women remained in the final analytic cohort ; 1567 men ( 227 with type 2 DM ) and 1242 women ( 108 with type 2 DM ) were diagnosed with colon or rectal cancer by 2007 . Among men , type 2 DM was associated with increased risk of incident CRC compared to not having type 2 DM ( RR : 1.24 ; 95 % CI : 1.08 - 1.44 ) ; risk was higher for participants with type 2 DM using insulin ( RR : 1.36 ; 95 % CI : 1.05 - 1.78 ) , and participants with type 2 DM not using insulin ( RR : 1.22 , 95 % CI : 1.04 - 1.45 ) . Among women , type 2 DM and insulin use were not associated with risk of incident CRC ( RR : 1.01 ; 95 % CI : 0.82 - 1.23 and RR : 0.95 ; 95 % CI : 0.64 - 1.41 , respectively ) . CONCLUSIONS There is a modest association between type 2 DM and CRC among men , but not women . Insulin use is not associated with a substantially increased risk of CRC We appreciate the discussion initiated by Badrick et al. ( 1 ) and thank them for the questions raised . In an ideal world , we would have a r and omized trial with the enormous sample necessary to answer this question as well as decades of follow-up . In an imperfect world , our analysis reveals the experience of a significant fraction of U.S. patients with diabetes using insulin glargine over 3 years of observation . Regarding our prevalent users cohort and fixed treatment group assignment , we acknowledged the reasonable but unproven assumption that our observed exposure reflects unobserved exposure , preceding 2006 ( Part D inception ) . Under this assumption , assignment to treatment observed in the earliest observation window is the best exposure We investigated the effects of metformin on the growth of lewis lung LLC1 carcinoma in C57BL/6J mice provided with either a control diet or a high-energy diet , previously reported to lead to weight gain and systemic insulin resistance with hyperinsulinemia . Forty-eight male mice were r and omized into four groups : control diet , control diet+metformin , high-energy diet , or high-energy diet+metformin . Following 8 weeks on the experimental diets , selected groups received metformin in their drinking water . Three weeks following the start of metformin treatment , mice were injected with 0.5x10(6 ) LLC1 cells and tumor growth was measured for 17 days . By day 17 , tumors of mice on the high-energy diet were nearly twice the volume of those of mice on the control diet . This effect of diet on tumor growth was significantly attenuated by metformin , but metformin had no effect on tumor growth of the mice on the control diet . Metformin attenuated the increased insulin receptor activation associated with the high-energy diet and also led to increased phosphorylation of AMP kinase , two actions that would be expected to decrease neoplastic proliferation . These experimental results are consistent with prior hypothesis-generating epidemiological studies that suggest that metformin may reduce cancer risk and improve cancer prognosis . Finally , these results contribute to the rationale for evaluation of the anti-neoplastic activity of metformin in hyperinsulinemic cancer patients |
1,283 | 10,796,860 | Amitriptyline ( another tricyclic ) was not consistently better than desmopressin either alone or when used as a supplement .
Combining alarm and drug therapy was found to be superior to alarm treatment alone .
REVIEW ER 'S CONCLUSIONS Desmopressin rapidly reduced the number of wet nights per week , but there was some evidence that this was not sustained after treatment stopped .
Comparison with alternative treatments suggested that desmopressin and tricyclics had similar clinical effects , but that alarms produced more sustained benefits .
However , the risk of water intoxication associated with over-drinking before bedtime has been reported . | BACKGROUND Enuresis ( bedwetting ) is a socially disruptive and stressful condition which affects around 15 - 20 % of five year olds , and up to 2 % of young adults .
Although there is a high rate of spontaneous remission , the social , emotional and psychological costs to the children can be great .
OBJECTIVES To assess the effects of desmopressin on nocturnal enuresis in children , and to compare desmopressin with other interventions . | The lack of circadian rhythmicity of plasma arginine vasopressin ( AVP ) in primary nocturnal enuresis ( PNE ) in some children is known . The original test protocol is time-consuming and needs excellent compliance by children and parents . The goals of the presented study are the introduction of a simple screening test and the evaluation of the response of treatment using intranasal synthetic vasopressin . Fifty-five children ( aged 8.2 + /- 3.1 years ) with PNE and 15 children ( aged 7.9 + /- 2.4 years ) of a control group were investigated . Using a st and ardized protocol , AVP levels were measured by radioimmunoassay ( RIA ) under controlled water intake 3 times per day over a period of 72 h. Fourteen of 55 tested children ( 25.5 % ) with PNE had a significant decrease in nocturnal AVP when compared to the control group . We measured also an increased nocturnal urine volume and a lower urine osmolality in this enuretic group . Eight of 14 patients ( 57.1 % ) with plasma AVP deficiency ( AVPD ) also had bladder instability . Nine of 14 patients ( 64.3 % ) with AVPD with or without concomitant bladder instability were totally dry during desmopressin treatment , but only 2 ( 14.3 % ) remained dry after discontinuation of treatment . Our data suggest that nocturnal urine osmolality measurement may reflect AVPD and predict a positive treatment outcome The effect of 20 micrograms . desaminocysteine-D-arginine vasopressin intranasally on childhood nocturnal enuresis was studied in a r and omized double-blind cross-over series of 54 children . The wetting was significantly less frequent during the 2 , 3-week periods on desaminocysteine-D-arginine vasopressin than during placebo periods , or during periods without any treatment . The effect of desaminocysteine-D-arginine vasopressin was reproducible and the efficacy of desaminocysteine-D-arginine vasopressin depended on the frequency of wetting before treatment . After discontinuation of the short treatment enuresis recurred immediately . No side effects were noted . We conclude that desaminocysteine-D-arginine vasopressin may well be used in the management of childhood enuresis , especially in situations when an immediate effect is desirable Fifty children with primary nocturnal enuresis were r and omised for a study comparing desmopressin ( DDAVP ) and enuresis alarm . Forty six completed the trial , 24 of whom were treated with 20 micrograms intranasal desmopressin nightly and 22 with enuresis alarm for three months . Failures were crossed over and relapses were continued on the same treatment for a further three months . The improvement rate was 70 % in the group given desmopressin and 86 % in the group treated with alarm ; the difference was not significant . During the first week of treatment the group given desmopressin was significantly dryer , and at the end of the study 10 of these patients relapsed compared with one patient in the group given the alarm . No serious side effects were observed . This study confirms the role of conditioning treatment as preferable in long term treatment of nocturnal enuresis . When this fails or when a safe drug with rapid effect is needed , however , desmopressin is a useful alternative OBJECTIVES To assess whether the synthetic vasopressin analogue desmopressin [ 1-desamino 8-D-arginine vasopressin ] is efficacious and safe in the management of nocturia + /- enuresis in patients with multiple sclerosis . PATIENTS AND METHODS Twenty-two women and 11 men , under 65 years of age , with clinical ly definite multiple sclerosis and nocturnal frequency + /- enuresis were entered into the study . A two week placebo run-in , to establish normal voiding patterns , followed by a double-blind , placebo-controlled , cross-over study of 20 micrograms intranasal desmopressin at night-time was carried out . RESULTS Desmopressin caused a significant decrease in nocturnal urinary frequency , nocturnal urinary volume and the percentage of total daily urine passed at night . There was no significant fall in plasma sodium with desmopressin although there were two cases of asymptomatic hyponatraemia . CONCLUSION Desmopressin is an efficacious and safe treatment for nocturia + /- enuresis in patients with multiple sclerosis The response of desamino-D-arginine vasopressin ( DDAVP ) was investigated in 32 enuretic children in a double-blind clinical study . The 15 children treated with DDAVP showed a significant reduction in the incidence of bed wetting -- from 18.7 + /- 6.5 to 6.5 + /- 9.2 wet nights per 30 days . In 6 children bed wetting stopped entirely , in 6 there was a satisfactory response , and in 3 the response was marginal or there was none . When DDAVP was stopped most children reverted to their earlier bedwetting habits ( 15.7 + /- 8.9 nights a month ) . Response to DDAVP was significantly better in children aged more than 10 years ( mean age for the entire group ) . The administration of DDAVP was not associated with any appreciable change in morning urine osmolalities . No adverse effects were noted . It is concluded that DDAVP is effective in nocturnal enuresis , particularly in older children . It is suggested that the cessation of bed wetting may , in part , reflect functional properties of DDAVP rather than antidiuresis To characterize the children with enuresis likely to respond to desmopressin acetate , we performed a double-blind crossover study that included the use of a placebo . During the two weeks of desmopressin administration , six children ( 12 % ) had 13 or 14 dry nights , and 15 children ( 29 % ) had eight to 12 dry nights . Among the 17 children aged 9 years or older , with four to seven dry nights during the two-week baseline period , 12 children ( 71 % ) responded to desmopressin ( eight to 14 dry nights ) . In contrast , none of the 15 children younger than 9 years of age with fewer than three dry nights before therapy responded . During the posttreatment period , only four of the 21 drug responders reported a persistent effect . Desmopressin may be effective in reducing the frequency of enuresis , especially in children older than 9 years of age without nightly enuresis During the period from March to September 1989 , 40 children suffering from primary nocturnal enuresis , aged between 5 and 14 years , were included in a study to assess the comparative therapeutical efficacy of DDAVP and acupuncture . Children were divided into four groups of 10 : group A was treated with DDAVP , group B was treated with acupuncture , group C was treated with DDAVP and acupuncture and group D was treated with placebo ( control ) . The trial design included 3 periods : observation ( 2 weeks ) , treatment ( 8 weeks ) and follow-up ( 4 weeks ) . Nineteen children completed the study . The efficacy of treatment , which was expressed as a percentage of dry nights , was high in both the DDAVP and acupuncture groups , when used separately . The combined treatment of DDAVP and acupuncture appeared to be the most efficacious both in terms of the percentage of dry nights at the end of treatment and in relation to the stability of results , even after the end of the study . The paper gives a detailed analysis of correlations between type of treatment and urinary osmolarity OBJECTIVE The aim of the study was to compare the efficacy and safety of different doses of DDAVP spray treatment ( 20 to 40 mcg/day ) in patients with primary monosymptomatic nocturnal enuresis ( defined as three or more wet nights per week ) . MATERIAL AND METHODS 237 patients ( 152 males , 75 females ; age range 5 - 17 years ) , with no infections or organic abnormalities of the urinary apparatus and no neurological disorders , were admitted into the trial . The experimental design was planned as an " open study " with five different treatments schedules ( 5 groups ) . The daily doses of DDAVP at bedtime in groups 1 and 2 were 20 and 30 mcg , respectively , for 6 weeks . In groups 3 and 4 the daily doses for the first 2 weeks were 20 and 30 mcg , respectively , and then , after a washout period of 2 weeks , the daily doses for the two groups were 30 and 20 mcg , respectively . A dose-response study ( 20 to 40 mcg/day ) was carried out in group 5 . RESULTS DDAVP spray therapy in primary monosymptomatic nocturnal enuresis was found to be resolutive in 70 - 75 % of treated patients . No difference in response was found between the patients treated with the daily dose of 20 and those on 30 mcg . No important reactions were observed in patients treated with DDAVP spray at the different daily dose ( 20 to 40 mcg ) or for different periods of time ( up to 6 weeks ) . CONCLUSIONS DDAVP spray therapy at a dose of 20 mcg/day was effective in 70 - 75 % of primary monosymptomatic nocturnal enuretics . In non-responders the daily dose of DDAVP should be increased to 30 to 40 mcg The effect of desamino-D-arginine vasopressin was investigated in a double-blind study of 37 children more than 9 years old with nocturnal enuresis resistant to conventional therapy . A significant reduction of wet nights was observed but as soon as the medication was stopped the children reverted to earlier bedwetting habits PURPOSE Desmopressin nasal spray has proved to be efficacious treatment of primary nocturnal enuresis . Oral desmopressin tablets would be a more easily used , convenient vehicle for our patients and their parents . We evaluated the effectiveness of oral desmopressin in decreasing the number of wet nights in patients with primary nocturnal enuresis . MATERIAL S AND METHODS We performed a double-blind , placebo controlled , parallel group trial of oral desmopressin in 141 children 5 to 17 years old with documented primary nocturnal enuresis at 14 sites . Patients were screened for number of wet nights for 2 weeks before study entry . A minimum of 3 wet nights weekly for 2 consecutive weeks was required for study entry . Patients were r and omized to receive 200 , 400 or 600 mcg . desmopressin or placebo before bedtime . Fluids were restricted 2 hours before bedtime based on body weight . The primary efficacy variable was mean decrease in the number of wet nights recorded during the last 2-week treatment period . The percentage of responding patients and mean decrease from baseline in number of wet nights at 2 , 4 and 6 weeks were also assessed . RESULTS The decrease in wet nights was 9 , 20 , 30 and 36 % for placebo , and 200 , 400 , and 600 mcg . desmopressin orally per day , respectively . The 600 mcg . dose of oral desmopressin daily was statistically significantly different ( p < 0.05 ) from placebo in decreasing wet nights . A complete or near complete response ( 0 to 2 wet nights ) was noted in 3 , 18 , 33 and 24 % of the patients who received placebo , and 200 , 400 and 600 mcg . oral desmopressin daily , respectively . The 400 and 600 mcg . treatment groups were statistically significantly different ( p < 0.05 ) from placebo . A less than 50 % decrease in wet nights was noted in 83 , 79 , 64 and 61 % of the patients who received placebo , and 200 , 400 and 600 mcg . oral desmopressin daily , respectively . Oral desmopressin exhibited a dose response in the treatment of primary nocturnal enuresis . The linear trend for the decrease in wet nights was statistically significant ( p < 0.05 ) . CONCLUSIONS A dose of 600 mcg . oral desmopressin daily significantly decreased the mean number of wet nights when administered for 6 weeks . A higher dose may be necessary for an improved response PURPOSE The use of desmopressin in patients with primary nocturnal enuresis is based on the hypothesis of a nocturnal lack of endogenous arginine vasopressin . However , in addition to the kidney , other targets of desmopressin are known . Therefore , we examined whether the administration of desmopressin influences central nervous function in children with primary nocturnal enuresis . MATERIAL S AND METHODS Our prospect i ve , r and omized , double-blind , placebo controlled cross-over study was performed on 40 children with nocturnal enuresis . Patients were r and omly assigned to receive either 20 microg . desmopressin intranasally or 0.9 % saline solution . Each group comprised 19 and 21 to children , respectively . After 2 weeks the groups were switched . The children were tested for short-term memory and reaction time to both treatments . Statistical analysis was done using the Wilcoxon matched pairs test . RESULTS Median patient age was 8.0 years ( range 6 to 13 ) . During desmopressin treatment children in both groups had a significant decrease of wet nights ( 5.3 to 3.2 per week ) . In contrast to reaction time , short-term memory was significantly different between both groups ( p < 0.05 ) . CONCLUSIONS Our results demonstrate an increase in short-term memory after desmopressin treatment in children with nocturnal enuresis . This finding indicates the central nervous system as a target involved in the pathogenesis of nocturnal enuresis as well as the therapeutic benefit of desmopressin treatment BACKGROUND Previous studies have suggested changes in self-concept with successful treatment of primary nocturnal enuresis ( PNE ) , but behavioral changes have not been reported as a consistent associated finding . OBJECTIVE To determine if self-concept and behavior change after 6 months of treatment of monosymptomatic PNE by conditioning alarm or desmopressin acetate ( DDAVP ) . DESIGN R and omized , controlled trial in an inner-city hospital clinic . Subjects were 182 children referred or recruited through media publicity , r and omly assigned both to 1 of 8 pediatricians and 1 of 3 treatment groups ( alarm , DDAVP , or placebo ) . Included were children > 7 years old with PNE , no daytime symptoms , bladder capacity > 50 % expected , and wetting > 3 times a week . Excluded were children with central nervous system disorders or developmental delays , and those currently on DDAVP or alarm . Subjects completed the Piers-Harris Children 's Self-Concept Scale and Harter 's Perceived Competence Scale for Children ( PCSC ) at initial visit and after 6 months of treatment . Parents completed the Achenbach Child Behavior Checklist ( CBCL ) at the same times . RESULTS After 6 months of treatment the Piers-Harris total score showed a highly significant treatment by period interaction effect for DDAVP , a significant effect for alarm , and no effect for placebo . For children who achieved 75 % dryness the CBCL showed a treatment by improvement interaction effect that was highly significant for DDAVP and placebo with no effect for alarm . For the PCSC there were no treatment or outcome interaction effects . After 6 months of treatment there were significant changes over time unrelated to outcome or treatment in the Piers-Harris Subscales and in the CBCL Internalizing and Externalizing Scores , and the Social Thought and Attention Problems Subscales . The PCSC was more stable with no changes in total score , and positive changes over time in only 2 Subscales , Scholastic and Social . CONCLUSION Children 's self-concept improved with the type of treatment and amount of success . Parents ' perceptions of behavior improve with type of treatment and amount of success . Children rate their self-concept and some physical attributes better after treatment with any of DDAVP , alarm , or placebo regardless of outcome . Frequent follow-up with emotional support and encouragement appear to be important components of an efficacious intervention for children with nocturnal enuresis The combination of desmopressin ( DDAVP ) and behavioral therapy for treatment of nocturnal enuresis was compared with use of each of these modes alone . We r and omly assigned 226 enuretic children being treated in primary care clinics of a major medical center in the largest health maintenance organization in Israel into 3 groups : Group A ) DDAVP plus behavioral therapy ( double-blind ) ; Group B ) behavioral therapy plus placebo ( double-blind ) ; and Group C ) DDAVP alone ( open group ) . DDAVP ( 20 micrograms/naris ) and placebo were administered by intranasal spray . Both pharmacologic and behavioral therapy were initiated after a 2-week observation period and continued for 8 weeks . All patients were followed for 2 months after completion of treatment . A significant reduction in the number of wet nights/week was registered for all 3 groups : 49 % in Group A , 45 % in Group B , and 19 % in Group C. After controlling for confounding factors , no significant difference in effect was noted among the 3 types of treatment during the trial period . However , on follow-up the results for the DDAVP patients were significantly less stable compared with the other 2 groups ( p = 0.015 ) . Minor side effects were registered , but none of the participants withdrew from the trial . To our knowledge , this is the largest r and omized trial of nocturnal enuresis conducted to date . Our findings suggest that simply discussing the problem with the patient and family leads to improvement , and that behavioral therapy is also beneficial . DDAVP can help , but the relapse rate on discontinuation is high A single blind dose response study of the effects of treatment with tablets containing 50 - 400 micrograms of desmopressin was conducted in 15 children with primary nocturnal enuresis . A dose response effect was seen , with the 100 , 200 , and 400 micrograms doses result ing in significantly more dry nights than when a placebo was used . The response after 200 micrograms was significantly different from that after 100 micrograms ( p less than 0.02 ) but not from that after 400 micrograms . A r and omised , double blind , double dummy , cross over study was then carried out in 30 children to compare the effects of a 20 micrograms dose given through a nasal pipette , a 200 micrograms tablet , and a placebo . The numbers of dry nights were significantly greater during both periods of treatment with desmopressin when compared with that using placebo , but there were no differences between the methods of taking the drug . After oral and nasal treatment 41 % and 52 % , respectively , of the patients improved by more than 50 % . Nine children ( 31 % ) remained completely dry after treatment Seventy‐one children with nocturnal enuresis were enrolled in a controlled trial . The children were allocated to two matched groups . Children in both groups used an enuresis alarm until the end of treatment . Children in the first group were treated with 40/^g of intranasal desmopressin ( Desmospray ) for up to 6 weeks at the start of treatment with the alarm . During the observation period before treatment there were 2.3 dry nights per week in both groups . At the end of treatment there was a significant difference in the mean number of dry nights per week between the two groups ( 6.3 in the alarm and desmopressin group and 4.8 in the alarm group ) and also in the number of children becoming reliably dry . The combination of desmopressin and alarm was particularly helpful for children with severe wetting and those with family and behavioural problems . Desmopressin , enuresis alarm , nocturnal Twenty-four adolescents , mean age 13.5 years , with primary nocturnal enuresis ( PNE ) , were studied to evaluate the efficacy of long-term oral desmopressin use . Reduction in mean number of wet nights per week was the criterion for response . Results showed that during 12-week treatment Period I , 48 % were full responders ( ≤1 wet night/wk ) ; 22 % were intermediate responders ( 2 to 3 wet nights/wk ) ; and 30 % were nonresponders ( > 3 wet nights/wk ) . During 12-week treatment Period II , 53 % were full responders , 23.5 % were intermediate responders , and 23.5 % were nonresponders . Despite a high relapse rate ( 50 % after Period I , 56 % after Period II ) , 17 patients ( 71 % ) were completely dry 2 years posttreatment , suggesting a possible curative effect of oral desmopressin . It was concluded that oral desmopressin is comparable to the intranasal formulation , with a good , long-term therapeutic effect in adolescents with PNE PURPOSE We confirmed findings that oral desmopressin safely decreases the number of wet nights in children with enuresis and identified doses at which acceptable responses can be obtained . MATERIAL S AND METHODS We evaluated the safety and efficacy of oral desmopressin in a double-blind , placebo controlled , parallel group , r and omized , multicenter trial of 193 children 6 to 16 years old with documented primary nocturnal enuresis . The study was conducted in 2 phases : 1 ) a 2-week dose ranging phase in which children received desmopressin ( 0.2 , 0.4 or 0.6 mg . ) or placebo at bedtime and 2 ) an 8-week dose titration phase that followed a 2-week placebo washout . Patients received 0.2 mg . desmopressin or placebo for the first 2 weeks and then the dose was increased in 0.2 mg . increments at 2-week intervals until the patient was completely dry or was receiving 0.6 mg . Patients were instructed to limit fluid intake . Mean decrease from baseline in the number of wet nights , percentage of responding patients and safety were assessed at 2-week intervals . RESULTS There was a statistically significant linear response to oral desmopressin at doses from 0.2 to 0.6 mg . during the dose ranging phase ( p < or = 0.05 ) . The decrease in wet nights after 2 weeks of treatment with desmopressin was 27 % , 30 % and 40 % at 0.2 , 0.4 and 0.6 mg . doses , respectively , compared to 10 % with placebo . All doses were statistically significantly different from placebo ( p < or = 0.05 ) . During the dose titration phase all placebo treated and 87 % of desmopressin treated patients were receiving the maximum dose of 3 tablets nightly because they had not been completely dry in the previous 2 weeks . Nevertheless , 44 % of desmopressin treated patients had achieved at least a 50 % reduction from baseline in the number of wet nights per 2 weeks at the lower doses of 0.2 and 0.4 mg . Most adverse events ( rhinitis , pharyngitis , headache and increased cough ) were mild to moderate in severity , unrelated to treatment and resolved before the study was completed . CONCLUSIONS Oral desmopressin administered at bedtime to children with primary nocturnal enuresis was significantly better than placebo for decreasing episodes of bed-wetting ( p < 0.05 ) . A linear dose-response relationship was observed ( p < 0.05 ) . An acceptable response to treatment ( 50 % or greater reduction from baseline in wet nights per 2 weeks ) was seen at all doses of desmopressin . Oral desmopressin , up to 0.6 mg . for 8 weeks , was well tolerated Fifty five children with nocturnal enuresis referred to a hospital enuresis clinic entered a controlled trial to compare the efficacy of one month and three month courses of intranasal desmopressin ( Desmospray ) . There was no significant difference in outcome between the two groups . Overall 36 % improved by at least two dry nights/week during treatment , but only five children ( 18 % ) in the one month group and three ( 11 % ) in the three month group became completely dry and only one in each group remained dry after treatment . To determine whether nocturnal polyuria was associated with a therapeutic response to desmopressin , the nocturnal urine volume , osmolality , and vasopressin concentration were measured in desmopressin responsive enuretics , desmopressin non-responders , and non-enuretic control children . There were no significant differences between the three groups . A three month course of desmopressin is no more effective than a one month course . Although many children will improve during treatment , only a small number become dry and most will relapse when treatment is stopped Abstract Sixty-two children with nocturnal enuresis ( 43 boys , 19 girls aged 6–15 years ) were treated with either desmopressin ( Adiuretin-SD ) ( n=32 ) or sodium diclofenac ( n=30 ) . Desmopressin was effective in 85 % of children and diclofenac in 33 % . In children with primary nocturnal enuresis , the glomerular filtration rate was normal , whereas diuresis and solute excretion during the night were increased . Compared with healthy children , the nightly excretion of sodium was elevated by 43.7 % and magnesium by 58.4 % . A high correlation was found between the free water reabsorption and solute clearance ( P<0.001 ) in children with nocturnal enuresis . Changes in kidney function in nocturnal enuresis appear to be due to a decrease in the water and ion reabsorption in the thick ascending limb of Henle ’s loop because of a changed regulation of ion transport in this part of the nephron . Administration of desmopressin or a decrease in prostagl and in production after diclofenac administration restores the ion and water transport in the kidney , which results in the disappearance of nocturnal enuresis . The results indicate a role of changes in regulation of ion transport in renal tubules in the pathogenesis of one of the forms of primary nocturnal enuresis OBJECTIVE Different etiopathological mechanisms of enuresis are today under study , and different therapies and drugs have been proposed . The Italian Multicentric Trial was undertaken in twelve pediatric and urological centers in order to assess the efficacy of two of the most popular drugs , desmopressin ( DDAVP ) and oxybutynin . METHODS 114 enuretic patients were enrolled in the study . After a 2-week observation period , 66 patients with primary monosymptomatic enuresis were treated with DDAVP , 30 micrograms/day intranasally , for 6 weeks , 48 patients with enuresis and voiding dysfunction were r and omly assigned to a protocol with oxybutynin alone or oxybutynin plus DDAVP . The efficacy of the two drugs was measured in terms of reduction of wet nights per week during the 6-week treatment period and a 2-week follow-up period . Children with 0 - 3 dry nights/week were considered as nonresponders . RESULTS Patients with monosymptomatic enuresis treated with DDAVP reported a significantly lower number of wet night during treatment than during the baseline period , with 79 % showing a ' good ' ( 6 - 7 dry nights/week ) or ' intermediate ' response ( 4 - 5 dry nights/week ) . Of the patients with diurnal voiding disturbances and enuresis , those treated with oxybutynin alone had a 54 % success rate . The patients treated with both oxybutynin and DDAVP showed a better response , with a 71 % rate of success . CONCLUSIONS The efficacy of the two drugs is confirmed in patients carefully selected on the clinical basis of voiding disturbances . In patients with enuresis and voiding dysfunction , the reduced urinary output and the lower bladder filling rate due to DDAVP can reduce uninhibited bladder contractions , thus enhancing the oxybutynin action Patients with primary nocturnal enuresis were entered into 4 treatment groups : observation , imipramine , desmopressin acetate or alarm therapy . Patients were weaned from therapy 6 months after inclusion in the study and were evaluated for continence at 3 , 6 , 9 and 12 months after beginning the study protocol . Of the 50 patients under observation 6 % were continent at 6 months and 16 % were continent within 12 months . Of 44 patients treated with imipramine 36 % were continent at 6 months on medication ; however , only 16 % were continent at 12 months , off medication . Similarly , of the 88 patients treated with desmopressin acetate 68 % were continent at 6 months but only 10 % were continent at 12 months . Of the 79 patients treated with alarm therapy 63 % were continent at 6 months and 56 % were dry at 12 months . Although each form of therapy improved continence over observation alone ( p < 0.01 ) , only the bed-wetting alarm system demonstrated persistent effectiveness ( p < 0.001 ) Forty-five children aged 6–14 years with primary nocturnal enuresis were r and omised to determine whether desmopressin is more effective than amitriptyline and whether the combination of amitriptyline/desmopressin is more effective than amitriptyline or desmopressin alone . Amitriptyline dosage was 25 mg for children 6–10 years and 50 mg for children aged 10–14 years . Desmopressin ( 20 μg ) was given in the same dosage for all age groups . After a run-in period of 2 weeks , children were treated for 16 weeks and then observed for 12 weeks . In the amitriptyline group mean wet nights per week decreased from 5.8±0.9 to 3.3±1.9 ( P<0.0005 ) ; in the desmopressin group mean wet nights per week decreased from 6.0±0.9 to 4.7±1.7 ( P<0.02 ) ; in the amitriptyline/desmopressin group mean wet nights per week decreased from 6.3±0.9 to 3.3±2.5 ( P<0.0006 ) . When comparing the groups , amitriptyline/desmopressin and amitriptyline were statistically more effective than demopressin in week 6 ( P<0.009 ) , week 8 ( P<0.03 ) and week 10 ( P<0.04 ) . No significant side effects occurred . At this dose amitriptyline was more effective than desmopressin and the combination of desmopressin and amitriptyline did not confer any additional benefit UNLABELLED The aim of the present studies was to investigate background factors and treatment in children with monosymptomatic primary nocturnal enuresis . The study material comprised enuretics , former enuretics and controls from the municipal community of Falkenberg on the west coast of Sweden . Whenever possible all investigations were made with the children staying in their own home environment . Different background factors have been suspected as being causative : sleep disturbances , behavioural or psychological disturbances , small bladder capacity , increased night diuresis and an insufficient production of the antidiuretic hormone during sleep . These factors have been investigated in these studies . The treatment of enuresis has been dominated by the alarm and antidiuretic treatment with DDAVP . Primary nocturnal monosymptomatic enuresis is a common problem in childhood . In this study the prevalence among 392 seven year old children was 7.3 % . A prior history of enuresis was found in 65 % of families of the enuretics compared to 25 % in controls . The enuretic children showed no statistically significant differences in behavioural or psychological problems compared to non-enuretic children . Enuretic children were described as heavy sleepers by their parents and a wake-up test performed at home showed that they were statistically significantly harder to arouse than the controls . Children with nocturnal enuresis , former enuretics and controls did not differ in social or behavioural traits in an interview study . No signs of symptom substitution was found when enuresis was resolved . Enuretic children had a normal bladder capacity and no statistically significant difference was found compared to controls and former enuretics . The enuretic children showed a normal calcium-creatinine quota in the urine . Former enuretic children showed a significantly enhanced calcium/creatinine quota compared to enuretics and controls . Enuretic children had a statistically significant lower morning plasma level of the anti diuretic hormone vasopressin than non-enuretic children . Enuretic children were treated for 12 weeks with DDAVP or the alarm . DDAVP treated patients had a more rapid effect compared with alarm treated patients . Alarm treated children had a lower relapse frequency . Enuretic children were treated in a r and omised , double blind , double dummy , cross over , placebo-controlled study with DDAVP 20 micrograms intranasally by a single dose pipette or 200 micrograms orally as a tablet . Both methods were equally effective in controlling enuresis , but significantly superior to placebo . CONCLUSION Enuretic children are normal , well adjusted children with a normal bladder capacity , a high level of arousal threshold , and a low morning level of plasma vasopressin . The alarm and DDAVP are equally effective in treating enuresis . ( ABSTRACT TRUNCATED AT 400 WORDS PURPOSE We evaluated the efficacy and safety of 2 oral doses of desmopressin compared to 20 micrograms . nasal spray and baseline values in the treatment of primary nocturnal enuresis . MATERIAL S AND METHODS A multicenter study was done comparing oral dosages ( 200 and 400 micrograms . ) of desmopressin ( 4-week , r and omized , double-blind phase followed by 12 weeks of open label treatment with 400 micrograms . ) to 20 micrograms . nasal spray in 66 adults and adolescents 12 to 45 years old with primary nocturnal enuresis . RESULTS No significant differences were found between the 2 doses of desmopressin tablets or between the tablets and 20 micrograms . nasal spray during the double-blind phase . However , patients who initially received 200 micrograms . desmopressin tablets experienced fewer wet nights after they completed 12 weeks of open label treatment when the dose was escalated to 400 micrograms . tablets . Those who received 400 micrograms . tablets initially maintained response during this phase . Desmopressin tablets were well tolerated at both dose levels : 96 % of patients and 94 % of physicians rated the tolerability as excellent . CONCLUSIONS Desmopressin tablets are an effective and safe alternative for treatment of nocturnal enuresis BACKGROUND In recent years the treatment of primary nocturnal enuresis ( PNE ) with desmopressin ( DDAVP ) has been promising . The route of administration until now had been intranasal , but because the tablets were introduced for the treatment of diabetes insipidus they have also become available for the treatment of PNE . OBJECTIVES To find the optimal dosage of desmopressin tablets and to compare desmopressin 's efficacy with placebo in a group of adolescents with severe monosymptomatic enuresis . The long-term safety of desmopressin was also studied in the same group of patients . METHODS The effect of oral desmopressin ( 1-deamino-8-D-arginine-vasopressin ) ( DDAVP tablets , Minirin ) was investigated in 25 adolescents ( ages 11 to 21 years ) with severe monosymptomatic nocturnal enuresis . The first part of the dose-ranging study comprised a single-blind dose titration period , followed by a double-blind , crossover efficacy period comparing desmopressin with placebo . The final part was an open long-term study consisting of two 12-week treatment periods . The efficacy of the drug was measured in reductions of the number of wet nights per week . RESULTS During the first dose-titration period , the majority of the patients were given desmopressin 400 micrograms , and the number of wet nights decreased from a mean of 4.9 to 2.8 . During the double-blind period , a significant reduction of wet nights was observed ( 1.8 vs 4.1 for placebo ) . During the two long-term periods , 48 % and 53 % of the patients could be classified as responders ( 0 to 1 wet night per week ) and 22 % and 23.5 % as intermediate responders ( 2 to 3 wet nights per week ) . No weight gain was observed due to water retention . After cessation of the drug , 44 % of the patients had a significant decrease in the number of wet nights . CONCLUSIONS Oral desmopressin has a clinical ly significant effect on patients with PNE , and therapy is safe when administered as long-term treatment The efficacy and safety of desmopressin ( Minirin/DDAVP ) treatment compared with imipramine were investigated in a multicentre , open , cross-over design in 57 patients , aged 6 - 15 years , affected by nocturnal enuresis to establish the best therapeutic approach to this condition . After a two-weeks observation and control period , patients were r and omised to one of two groups : intranasal administration of desmopressin , 30 micrograms/day for three weeks , followed by imipramine , 0.9 mg/kg for a further three weeks , or imipramine 0.9 mg/kg for three weeks , followed by desmopressin , 30 micrograms/day for a further three weeks . Following treatment , all patients were observed for a further two weeks . Administration of either treatment protocol result ed in a statistically significant decline in the number of enuretic episodes per week compared to the control . The greater antidiuretic effect observed in the group receiving imipramine followed by desmopressin suggests the two compounds have different profiles . Also , when the treatment period was compared with the follow-up , the antidiuretic effect had a longer duration in the group initially given imipramine . No further improvement was seen when desmopressin was administered first , with a mild worsening of the effect sometimes occurring , suggesting a different carry-over effect between the two treatments . This suggests that desmopressin offers a better approach to the management of nocturnal enuresis The effect of intranasal desmopressin on primary nocturnal enuresis was investigated in a study divided into 2 parts in which the first part was a r and omized , double-blind , placebo-controlled cross-over study of 52 Finnish school children 5 to 13 years old . A variety of approaches had previously been attempted in most children , including water deprivation , night awakenings , enuresis alarm and imipramine , without success . The patients were r and omized to 4 periods of 3 weeks each : 2 periods on placebo and 2 periods on 20 micrograms . desmopressin spray . The entire 12-week treatment period was preceded and followed by control periods ( without treatment ) . The number of dry nights , measured as calculated averages per week , increased significantly ( p less than 0.01 ) from 0.6 dry nights during pre-treatment to 4.3 and 4.6 dry nights per week during the 2 desmopressin treatment periods , respectively . The placebo responses were 2.1 and 2.4 dry nights per week , respectively . The second part of the study was an open dose-finding and drug safety study of a further 3 months in duration . The aim was to evaluate the efficacy and tolerance of 20 , 30 and 40 micrograms . doses . All 47 patients who relapsed during the post-treatment period in part 1 were included . During this period 53 % of the patients responded fully , 19 % were intermediate responders and 28 % did not respond . As reported in other studies most patients suffered relapse after treatment . During continued treatment for 3 months at doses between 20 and 40 micrograms . desmopressin was well tolerated , had no effect on body weight or blood pressure and did not cause any adverse reactions OBJECTIVE To study the long-term efficacy and safety of desmopressin treatment in children with primary monosymptomatic nocturnal enuresis . PATIENTS AND METHODS Children ( aged 6 - 12 years ) with nocturnal enuresis were recruited into an open multicentre trial . All children underwent an observation period of 4 weeks before starting a 6-week dose-titration period with desmopressin . If the number of wet nights decreased by more than half during medication , they began long-term treatment on 20 - 40 microg desmopressin . To test for cure and avoid overtreatment , the medication was interrupted for one week every third month . RESULTS Of the 399 children forming the intention-to-treat cohort , 245 halved their number of wet nights and started long-term treatment . During the periods off medication , 77 children were dry and at the end of the study another 73 ( still on medication ) reduced the number of wet nights to < or = 10 % of that during the observation period . A further 51 children halved the number of wet nights compared with the observation period . No serious adverse events occurred . CONCLUSION Long-term treatment with nasal desmopressin at a main dose of 40 microg is an effective and safe treatment for monosymptomatic nocturnal enuresis The efficacy and safety of 6 weeks of treatment with desmopressin tablets at doses of 200 to 400 micrograms.at bedtime were investigated in 33 children with monosymptomatic nocturnal enuresis . During an initial 1 to 2-week dose titration period 22 patients ( 67 % ) became either completely dry or showed improvement , 7 ( 21 % ) showed no response and 4 ( 12 % ) dropped out of therapy . During tablet treatment 17 patients on 400 micrograms . and 5 on 200 micrograms.at bedtime increased the number of weekly dry nights from 2.0 + /- 1.6 ( st and ard deviation ) during a 2-week observation period to 5.2 + /- 1.9 ( p < 0.001 ) . During a subsequent 2-week period 40 micrograms.intranasal desmopressin showed a similar overall efficacy , with a mean of 5.4 + /- 1.6 dry nights per week . In addition , intranasal treatment was able to increase the number of dry nights in 2 of the 7 nonresponders to tablet treatment OBJECTIVES To compare the efficacy of desmopressin and indomethacin and also determine the prostagl and in E2 ( PGE2 ) concentrations in the patient and control groups . METHODS Eighty-five children with primary nocturnal enuresis were followed up for a baseline period of 4 weeks , during which they recorded wet and dry nights . After this period , the patients were divided into three groups that used desmopressin , indomethacin , or placebo for 4 weeks . The dosage of desmopressin ( group A , n = 31 ) was 20 microg/day and the dosage of indomethacin ( group B , n = 29 ) was 100 mg/day . The placebo group ( group C ) consisted of 25 patients . We determined the serum PGE2 and urine PGE2 concentrations before and after treatment in the three groups and in a control group . RESULTS Treatment with desmopressin and indomethacin result ed in significantly more dry nights during the 4 weeks of observation than did placebo ( P < 0.005 ) . The number of dry nights was also significantly different in the desmopressin group than in the indomethacin group ( P < 0.01 ) . In the total patient group , the mean serum and urine PGE2 concentrations were significantly different from the control group 's serum and urine PGE2 concentrations ( P < 0.001 ) . There was a significant decrease in the serum and urine PGE2 concentrations in group A and group B after the treatment period ( P < 0.01 ) . CONCLUSIONS Desmopressin and indomethacin were found to be more effective than placebo . We conclude that prostagl and ins have an important role in the pathophysiology of primary nocturnal enuresis To determine if urine osmolality parameters can predict whether children with primary monosymptomatic nocturnal enuresis will respond to desmopressin , we conducted a prospect i ve , double-blind , placebo-controlled study in 96 children 8 to 14 years old . Following a 2-week baseline screening interval patients with at least 6 of 14 net nights were r and omized to double-blind regimens of desmopressin or placebo . Urine specimens for osmolality were collected at 6 p.m. and 6 a.m. on 3 consecutive days during the baseline and the 2 , 14-day treatment periods . A significantly greater proportion of desmopressin treated children had an excellent ( 2 or fewer wet nights in 14 days ) or good ( greater than 50 % reduction in wet nights ) response compared with placebo treated children ( p = 0.004 and p = 0.002 for treatment periods 1 and 2 , respectively ) . Children treated with desmopressin reported a significantly lower number of wet nights than placebo treated children during both treatment periods ( p = 0.0258 and p = 0.0136 , respectively ) . Children treated with desmopressin had a significantly higher 6 a.m. urine osmolality during both treatment periods and a higher 6 a.m.-to-6 p.m. osmolality ratio ( p = 0.004 ) in the first treatment period compared with the placebo group . Within the desmopressin treatment group clinical responders had a higher 6 a.m. urine osmolality and 6 a.m.-to-6 p.m. urine osmolality ratio than nonresponders during both treatment periods but these differences did not achieve statistical significance . In conclusion , treatment with desmopressin is associated with a significant decrease in the number of wet nights , and a significant increase in nocturnal urine osmolality and nocturnal/diurnal urine osmolality ratios . However , clinical response was not predictable based on baseline or treatment osmolality parameters A series of 22 patients with severe nocturnal enuresis were treated with desmopressin in a r and omised double-blind cross-over study . Treatment with 20 and 40 micrograms was highly effective compared with placebo . No difference in dry nights was found between the 2 dosages . Desmopressin proved to be a safe and effective treatment A double blind crossover trial of 20 micrograms intranasal 1-deamino-8-d-arginine vasopressin ( DDAVP ) versus placebo was carried out in 17 children with intractable enuresis aged between 6 and 13 years who had failed to respond to drugs and an enuresis alarm . Fluid intake was not restricted . There was a significant reduction in the number of wet nights . Seven children ( 41 % ) were cured or showed considerable improvement , with strong evidence against any placebo effect . The best response was seen in children aged 10 years or over and if urine osmolality after DDAVP reached beyond 1000 mmol/kg or was already at this concentration . The degree of overnight rise in urine osmolality after treatment with DDAVP was not predictable but correlated well with the clinical improvement in nocturnal diuresis present in eight of the children . A further 12 children with equally refractory enuresis were given 20 micrograms of the active drug to take during their school journeys or holidays . Six of them had previously normal overnight urine osmolalities with only two successes , but of the six who had nocturnal diuresis before treatment , five became dry , suggesting that DDAVP acts largely by anti-diuresis and might be most useful in children with nocturnal polyuria PURPOSE The relationship of functional bladder capacity as well as other variables to the responsiveness to desmopressin in children with monosymptomatic nocturnal enuresis was investigated . MATERIAL S AND METHODS A total of 95 children 8 to 14 years old with monosymptomatic nocturnal enuresis ( 6 or more of 14 nights wet ) were evaluated in a double-blind study followed by open label crossover extension using 20 to 40 mcg . desmopressin . Evaluated predictors of response included patient age , gender , race , family history , number of baseline wet nights , urine osmolality parameters and maximum functional bladder capacity ( as a percent of predicted bladder capacity based on the formula , patient age + 2 x 30 = cc ) . Responders to desmopressin were classified as excellent ( 2 or less of 14 nights wet ) or good ( 50 % or greater decrease but more than 2 of 14 nights wet ) and nonresponders were defined by a less than 50 % decrease in wet nights . RESULTS Of the 95 patients 25 ( 29.5 % ) achieved an excellent response to desmopressin and 18 ( 18.9 % ) had a good response for a cumulative response rate of 45.3 % . The remaining 52 patients ( 54.7 % ) were nonresponders . There were no significant differences between responders and nonresponders in regard to gender , race , positive family history or baseline urine osmolality parameters . Response to desmopressin was associated with older age , fewer baseline wet nights and larger bladder capacity . Patients with a functional bladder capacity greater than 70 % predicted bladder capacity were 2 times more likely to respond to desmopressin . CONCLUSIONS The responsiveness of children with nocturnal enuresis to desmopressin is adversely affected by reduced functional bladder capacity . The results of this study have implication s regarding the potential use of combination pharmacotherapy with desmopressin and an anticholinergic for enuretic patients who are nonresponsive to single drug therapy OBJECTIVE To measure the effect of intranasal desmopressin ( l-deamino 8-D-arginine vasopressin , DDAVP ) on urine osmolality in a group of patients with persistent primary enuresis , and to determine whether changes in osmolality can the predict response to treatment . PATIENTS AND METHODS Thirty-seven patients with persistent primary nocturnal enuresis were entered into a double-blind placebo-controlled crossover trial of 20 micrograms intranasal DDAVP spray . Morning urinary osmolality was measured on two occasions during each phase of treatment and the clinical response recorded in a diary . RESULTS Thirty-one patients ( 22 males and nine females ) were evaluable at the end of the trial period . A good clinical response , defined as enuresis on two nights or fewer each week , occurred in 12 of 31 ( 39 % ) patients , but complete continence was attained in only two . The response was better in older patients and in those with less frequent enuresis . The mean and peak urinary osmolality of the morning urine sample s were higher while on treatment with DDAVP compared with placebo , but this difference was not statistically significant and the response did not predict a good clinical outcome in improving the enuresis . CONCLUSIONS Treatment with DDAVP can produce a socially acceptable level of dryness in some patients with refractory nocturnal enuresis . However , the early morning urinary osmolality , as a reflection of changes in nocturnal osmolality , was not useful in distinguishing this group or in selecting those who will respond to treatment PURPOSE We tested the role of the bladder in the pathogenesis of desmopressin resistant enuresis by evaluating the influence of urine production on the timing of the enuretic event and the response to anticholinergic medication . MATERIAL S AND METHODS We gave 33 children with monosymptomatic nocturnal enuresis resistant to the st and ard 0.4 mg . oral dose of desmopressin 0.4 and 0.8 mg . desmopressin and placebo tablets for 5 nights each in a double-blind crossover fashion . The time of enuresis or nocturia was documented . All 9 children who had at least 1 dry treatment period during the r and omized portion of the study then received open label treatment with 0.8 mg . desmopressin . Nonresponders to this regimen and the remainder of the children were offered anticholinergic treatment . RESULTS Average time between bedtime and voiding was 5.0 , 5.6 and 5.0 hours during the nights with placebo , and 0.4 and 0.8 mg . desmopressin , respectively ( p = 0.12 ) . Of the 9 children subsequently treated with 0.8 mg . desmopressin 5 became completely dry . Of the remaining 28 children given anticholinergic treatment 20 responded . CONCLUSIONS Antidiuresis does not delay the enuretic event in children with desmopressin resistant enuresis . This finding and the favorable response to anticholinergic medication favor the hypothesis that these children have nocturnal bladder instability . A subgroup of enuretic children responds to high but not normal doses of desmopressin The purpose of this study was to determine the efficacy and safety of long-term treatment of nocturnal enuresis with desmopressin intranasal spray . Sixty-five children with primary nocturnal enuresis with a mean age of 11.3 years ( range 7 - 17 ) underwent a 2-week observation period followed by dose titration period of 1 week . Those children completely dry with desmopressin entered a r and omized , placebo-controlled , double-blind phase lasting 2 weeks , followed by a 6-month open treatment . The enuretic status of the children was documented for 2 weeks after the treatment was stopped . Eleven children had no change from baseline wetting with desmopressin . Thirty-two children receiving 20 mg and 9 children with 40 mg desmopressin were completely dry . Thirteen children were wet 1 - 2 nights per week , which was better than in the pretreatment period . During the 6-month open-treatment period , the effect of desmopressin was found to be stable . No side effects or adverse reactions were encountered . Two weeks after the treatment was stopped , 25 children were still completely dry ( 38 % of the initial study population , 50 % of the responders ) . The cure rate appeared to continue beyond 18 months after discontinuation of the treatment Desmopressin acetate , a synthetic antidiuretic drug , was evaluated in two US multicenter studies involving a total of 176 children with severe primary nocturnal enuresis . Patients who qualified during the screening period , entered a double-blind treatment phase during which they received 20 micrograms or 40 micrograms of desmopressin acetate or placebo at bedtime for four weeks . This phase was followed by a four-week open-label period , during which all patients received 20 or 40 micrograms of desmopressin acetate . In both studies , children given desmopressin acetate had significantly fewer wet nights after two and four weeks of therapy than did children given placebo . During the open-label period , patients crossed over from placebo to desmopressin acetate showed similar reductions in enuresis . Global evaluations by the patients , their parents , or the investigators further confirmed the good results with desmopressin acetate . No serious adverse experiences were reported . Thus the results of these studies corroborate previously published reports of the efficacy and safety of desmopressin acetate in the treatment of primary nocturnal enuresis The efficacy of alarm monotherapy ( 35 children ) was compared with the efficacy of alarm treatment in combination with 40 micrograms desmopressin ( Minirin , DDAVP ) nasal spray ( 36 children ) . At the end of the treatment period , children receiving combination therapy had more dry nights per week ( mean : 6.1 ) than children using an alarm alone ( mean : 4.8 ) . In addition , more children achieved an initial success ( 4 weeks of dryness ) following combination treatment ( 27 children [ 75 % ] ) compared with alarm monotherapy ( 16 children [ 46 % ] , P < 0.005 ) . This improvement with alarm plus desmopressin was particularly pronounced in children with severe wetting ( > or = 6 nights per week ) , family problems or behavioural problems . It may , therefore , be appropriate to manage children in these categories with an enuresis alarm supplemented with desmopressin to improve treatment outcome A response to desmopressin spray is only seen in a proportion of children with enuresis . To investigate whether response is related to nocturnal levels of arginine vasopressin ( AVP ) 35 children with enuresis , aged 8 to 14 years , had plasma AVP measurements overnight before entering a double blind r and omised , placebo controlled crossover study to assess their response to evening treatment with desmopressin spray . There was no significant difference seen between nocturnal AVP levels obtained from children who responded to desmopressin and those who did not . Frequent sampling in six children demonstrated a pulsatile pattern of secretion for AVP . This has implication s for studies of nocturnal AVP levels , and questions the validity of using infrequent measurements of AVP to assess it 's secretion ABSTRACT . A double‐blind study of 18 children aged 6–12 years suffering from primary nocturnal enuresis without signs of underlying organic disease is reported . 20 μg of DDAVP ( desamino‐d‐arginine vasopressin , Minirin ® ) was given intranasally at bedtime . The effect was prompt and satisfactory in 8 children and relatively good in another 8 children . No adverse effects were noted . DDAVP is advocated for temporary use in children with nocturnal enuresis needing immediate help PURPOSE We evaluated the combination of alarm and desmopressin versus alarm monotherapy for the treatment of nocturnal enuresis . MATERIAL S AND METHODS A double-blind , placebo controlled study of alarm therapy combined with desmopressin for children with nocturnal enuresis is described . Of 93 patients 47 were r and omized to receive alarm therapy and 40 microg . intranasal desmopressin for 3 weeks followed by 20 microg . desmopressin for 3 weeks ( group 1 ) and 46 received alarm therapy and placebo ( group 2 ) . After 6 weeks on alarm therapy and medication or placebo , both groups received an additional 3 weeks of alarm monotherapy . A specialized nurse practitioner advised patients and families of the treatment to be given at home and in the outpatient department . Bed-wetting frequency was evaluated before during and 2 weeks and 6 months after treatment . RESULTS A significantly greater reduction in the number of wet nights was observed after the first 3 weeks of treatment in group 1 . However , after long-term followup no significant differences in bed-wetting frequency were noted . CONCLUSIONS There is a temporary , positive effect on enuresis using desmopressin combined with alarm therapy . However , both treatment modalities have a low long-term success rate of 36 % to 37 % A double-blind cross-over trial of DDAVP was carried out in 22 patients aged between 9 and 16 years . The patients had previously failed to respond to other treatments for enuresis . While DDAVP result ed in fewer wet nights during the 14-day period of active treatment , the results did not achieve statistical significance . This is in contrast to previous reports . The dose in this study was 20 micrograms intranasally . Further studies may be valuable , possibly relating dosage to body weight OBJECTIVE To determine the efficacy and safety of oral desmopressin ( DDAVP ) treatment in Asian children with nocturnal enuresis . METHODOLOGY This was a multicentre r and omized placebo-controlled double-blind cross-over study . Patients were r and omized to either active treatment with oral 400 mg DDAVP or placebo , with a 2-week medication-free period between the cross-over . Children with primary monosymptomatic nocturnal enuresis , aged between 7 and 18 years , with a minimum frequency of wetting of 6 nights or more during a 2-week observation period were recruited . Efficacy was measured by reduction in the average number of wet nights per week . RESULTS Of the 37 children initially recruited , the outcomes for 34 children were included in the final cross-over analysis , as they had complete data for both the treatment periods . Statistical analysis by ANOVA showed that there was no significant difference between the medication-free period and the pretreatment period . However , the average number of wet nights per week for the DDAVP treatment period ( 2.5+/-2.7 ) was significantly lower than that of the placebo treatment period ( 4.5+/-2.1 ) ( P < 0.0001 ) . In terms of the safety profile , there was no significant change in bodyweight , blood pressure , serum sodium , serum osmolality , and urine osmolality following DDAVP treatment . CONCLUSION Oral DDAVP is a safe and efficacious drug for the short-term treatment of children with primary nocturnal enuresis Desmopressin ( 1-desamino-[8-D-Arg]-vasopressin ) ( DDAVP ) was given by nose drops to 22 children with persistent nocturnal enuresis ( mean age , 6.6 + /- 2.9 years ; range , 4 to 12 years ) the evening before sleep . With saline alone as placebo and with comparison to enuretic frequency before the onset of the trial , fortnightly periods were compared under double-blind conditions with the children at home . Pretreatment and placebo fortnights showed wetting frequencies ( nights per fortnight ) of 10.6 + /- 4.9 and 11.0 + /- 4.4 , respectively . The value of the fortnight during desmopressin therapy was 4.2 + /- 4.5 , which was significantly different from either of the previous means ( P less than .01 ) . Of the 22 subjects , four failed to react to therapy at all . There was decreased enuretic frequency in the remaining 18 , of whom 12 decreased markedly or ceased wetting . One month after the trial , seven of the respondents were dry with desmopressin therapy . There was clear evidence of a large nocturnal volume of dilute urine before treatment in six of the respondents in whom such measurements could be reliably made . These children responded to dehydration with urine concentration , however , so that the suggestion can be made that a failure to develop a normal diurnal pattern of urine volume and concentration may underly some cases of enuresis Objective : To evaluate the efficacy of intranasal desmopressin ( DDAVP ) and retention control training ( RCT ) for monosymptomatic nocturnal enuresis in childhood and to assess the predictive value of daytime functional bladder capacity for both methods . Material s and Methods : A total of 114 children with monosymptomatic nocturnal enuresis , of whom 99 ( 86.8 % ) wetted the bed every night , were treated with 1 of the 2 methods : intranasal DDAVP in 54 and RCT in 60 subjects . Results : Twenty – one of 54 patients ( 38.9 % ) and 14 of 60 patients ( 23.3 % ) in the DDAVP group and the RCT group , respectively , achieved strong improvement ( p = 0.061 ) . Forty – five of 54 ( 90.0 % ) in the DDAVP and 35 of 60 ( 58.3 % ) in the RCT group had a more than 50 % decrease in wet nights ( p = 0.004 ) . In the DDAVP group , the functional bladder capacities at baseline in responders and nonresponders were 82±22 % and 56±20 % of the predicted bladder capacity for their age ( p<0.001 ) . In the RCT group , responders and nonresponders did not differ in functional bladder capacity at baseline . Conclusion : DDAVP treatment is more effective than RCT in decreasing the number of wet nights in childhood nocturnal enuresis , but not so effective in children with a low functional bladder capacity . Daytime functional bladder capacity is a valuable predictor of response to DDAVP , but not so to RCT Objectives : Several treatment modalities for children suffering from monosymptomatic nocturnal enuresis are available , but desmopressin is a well – established option . On the other h and , alternative nonpharmacological therapies such as laser acupuncture are more frequently requested by the parents . To our knowledge , there is no prospect i ve r and omized trial which evaluated the efficacy of such an alternative approach in comparison with the widespread use of desmopressin . Methods : Forty children aged over 5 years presenting with primary nocturnal enuresis underwent a previous evaluation of their voiding function to assure normal voiding patterns and a high nighttime urine production . Then the children were r and omized into two groups : group A children were treated with desmopressin alone , and group B children underwent laser acupuncture . All children were investigated after a minimum follow – up period of 6 month to evaluate the duration of the response . Results : The children of both groups had an initial mean frequency of 5.5 wet nights per week . After a minimum follow – up period of 6 months reevaluation revealed a complete success rate of 75 % in the desmopressin – treated group . Additional 10 % of the children had a reduction of their wet nights of more than 50 % . On the other h and , 6 months after laser acupuncture , 65 % of the r and omized children were completely dry . Another 10 % had a reduction of the enuresis frequency of more than 50 % per week . 20 % of the children in the desmopressin – treated group did not respond at all as compared with 15 % in the acupuncture – treated group . Statistical evaluation revealed no significant differences among the response rates in both groups . Conclusion : I m comparison with pharmacological therapy using desmopressin , our study shows that laser acupuncture should be taken into account as an alternative , noninvasive , painless , cost – effective , and short – term therapy for children with primary nocturnal enuresis in case of a normal bladder function and high nighttime urine production . Success rates indicated no statistically significant differences between the well – established desmopressin therapy and the alternative laser acupuncture |
1,284 | 25,204,381 | Paper-based reminders were the most frequent with fully computerized , then computer generated , and other modalities .
No study reported a decrease in health care practitioner performance or declining patient outcomes .
The most common primary outcome measure was compliance with provided or prescribing guidelines , key clinical indicators such as patient outcomes or quality of life , and length of stay .
Conclusions Paper-based implementations are by far the most popular approach to implement a guideline or protocol .
Asthma guidelines generally improved patient care and practitioner performance regardless of the implementation method | Background Asthma is one of the most common childhood illnesses .
Guideline -driven clinical care positively affects patient outcomes for care .
There are several asthma guidelines and reminder methods for implementation to help integrate them into clinical workflow .
Our goal is to determine the most prevalent method of guideline implementation ; establish which methods significantly improved clinical care ; and identify the factors most commonly associated with a successful and sustainable implementation . | Abstract Objective : To evaluate the use of a computerised support system for decision making for implementing evidence based clinical guidelines for the management of asthma and angina in adults in primary care . Design : A before and after pragmatic cluster r and omised controlled trial utilising a two by two incomplete block design . Setting : 60 general practice s in north east Engl and . Participants : General practitioners and practice nurses in the study practice s and their patients aged 18 or over with angina or asthma . Main outcome measures : Adherence to the guidelines , based on review of case notes and patient reported generic and condition specific outcome measures . Results : The computerised decision support system had no significant effect on consultation rates , process of care measures ( including prescribing ) , or any patient reported outcomes for either condition . Levels of use of the software were low . Conclusions : No effect was found of computerised evidence based guidelines on the management of asthma or angina in adults in primary care . This was probably due to low levels of use of the software , despite the system being optimised as far as was technically possible . Even if the technical problems of producing a system that fully supports the management of chronic disease were solved , there remains the challenge of integrating the systems into clinical encounters where busy practitioners manage patients with complex , multiple conditions UNLABELLED Critics of the use of clinical practice guidelines ( CPGs ) in an emergency department ( ED ) setting believe that they are too cumbersome and time-consuming , but to the best of the authors ' knowledge , potential barriers to CPG adherence in the ED have not been prospect ively evaluated . OBJECTIVES To measure provider adherence to an ED CPG based on National Asthma Education and Prevention Program ( NAEPP ) recommendations , and to determine factors associated with provider nonadherence . METHODS Prospect i ve , cohort study of children aged 1 - 18 years with the diagnosis of an acute exacerbation of asthma who were seen in a pediatric ED and requiring admission , as well as a r and om selection of children discharged to home following pediatric ED care . The following adherence parameters were assessed : at least three nebulized albuterol treatments in the first hour ; early steroid administration ( after the first nebulizer treatment ) ; clinical assessment s using pulse oximetry and peak expiratory flow ( PEF ) ( for children > 6 years old ) ; and use of a clinical score to assess acute illness severity ( Asthma Severity Score ) . Nonadherence was defined as any deviation of the above parameters . RESULTS Between July 1 , 1998 , and June 30 , 1999 , 369 patients were studied . Of these , 38 % ( 139 ) were discharged to home , 38 % ( 140 ) were admitted to the observation unit , and 24 % ( 90 ) were admitted to the inpatient unit . Illness severities at initial presentation to the ED were : 24 % ( 86 ) had mild exacerbations , 59 % ( 212 ) had moderate exacerbations , and 17 % ( 62 ) had severe exacerbations . Sixty-eight percent ( 95 % CI = 63 % to 73 % ) of the patients were managed with complete adherence to the CPG . Of the 32 % with some form of nonadherence , most ( 63 % ) were children older than 6 years ; in this group 64 % ( 48/75 ) were nonadherent due to lack of PEF assessment . When PEF assessment was disregarded , an 83 % ( 95 % CI = 79 % to 87 % ) adherence to the CPG was achieved . Other nonadherence factors included : lack of at least three nebulized albuterol treatments provided timely within the first hour ( 5 % ) ; delay in steroid administration ( 6 % ) ; lack of pulse oximeter use ( 0.5 % ) ; and failure to record clinical score to assess severity ( 1.1 % ) . Patient age , illness severity ( acute and chronic ) , first episode of wheezing , and high ED volume periods ( evenings and weekends ) did not worsen adherence . CONCLUSIONS Clinical practice guidelines can be used successfully in the pediatric ED and provide a more efficient management and treatment approach to acute exacerbations of childhood asthma . With a systematic and concise CPG , barriers to adherence in a pediatric ED appear to be minimal , with the exception of using PEF in the routine ED assessment Background Internet-based self-management has shown to improve asthma control and asthma related quality of life , but the improvements were only marginally clinical ly relevant for the group as a whole . We hypothesized that self-management guided by weekly monitoring of asthma control tailors pharmacological therapy to individual needs and improves asthma control for patients with partly controlled or uncontrolled asthma . Methods In a 1-year r and omised controlled trial involving 200 adults ( 18 - 50 years ) with mild to moderate persistent asthma we evaluated the adherence with weekly monitoring and effect on asthma control and pharmacological treatment of a self-management algorithm based on the Asthma Control Question naire ( ACQ ) . Participants were assigned either to the Internet group ( n = 101 ) that monitored asthma control weekly with the ACQ on the Internet and adjusted treatment using a self-management algorithm supervised by an asthma nurse specialist or to the usual care group ( UC ) ( n = 99 ) . We analysed 3 subgroups : patients with well controlled ( ACQ ≤ 0.75 ) , partly controlled ( 0.75>ACQ ≤ 1.5 ) or uncontrolled ( ACQ>1.5 ) asthma at baseline . Results Overall monitoring adherence was 67 % ( 95 % CI , 60 % to 74 % ) . Improvements in ACQ score after 12 months were -0.14 ( p = 0.23 ) , -0.52 ( p < 0.001 ) and -0.82 ( p < 0.001 ) in the Internet group compared to usual care for patients with well , partly and uncontrolled asthma at baseline , respectively . Daily inhaled corticosteroid dose significantly increased in the Internet group compared to usual care in the first 3 months in patients with uncontrolled asthma ( + 278 μg , p = 0.001 ) , but not in patients with well or partly controlled asthma . After one year there were no differences in daily inhaled corticosteroid use or long-acting β2-agonists between the Internet group and usual care . Conclusions Weekly self-monitoring and subsequent treatment adjustment leads to improved asthma control in patients with partly and uncontrolled asthma at baseline and tailors asthma medication to individual patients ' needs . Trial registration Current Controlled Trials IS RCT This prospect i ve study was design ed to determine whether incorporating formoterol into a st and ardized respiratory therapist-directed protocol for administering bronchodilators to hospitalized patients with obstructive airway disease would reduce health care re source use and provide a safety advantage . All patients admitted to Washington Hospital Center with asthma and chronic obstructive pulmonary disease ( CODP ) are administered bronchodilators under a st and ardized respiratory therapist-directed protocol . Formoterol was the primary bronchodilator for the intervention period from January through March 2002 , with levalbuterol , albuterol , and ipratropium available as needed . Results for the intervention period were compared against two historical control periods . From January through March 2000 , the bronchodilators in the protocol were albuterol and ipratropium , and from January through March 2001 levalbuterol , albuterol , and ipratropium were available . Health care re source use was determined by the number of bronchodilator treatments administered per admission . Costs ( adjusted to 2002 dollars ) for supplies , therapist time , and drugs were calculated for the three time periods . Adverse events related to bronchodilator administration were recorded in a st and ardized manner for all three time periods . Bronchodilator treatments per admission , respiratory therapist visits per admission , and time spent per admission , and cost per bronchodilator treatment significantly decreased in 2002 . Significantly fewer adverse events related to bronchodilator treatments were reported in 2002 than 2000 . The addition of formoterol to a respiratory therapist-directed protocol for administering bronchodilators reduced health care re source use and adverse events for patients with asthma and COPD OBJECTIVE : Asthma continues to be 1 of the most common chronic diseases of childhood and affects ∼6 million US children . Although National Asthma Education Prevention Program guidelines exist and are widely accepted , previous studies have demonstrated poor clinician adherence across a variety of population s. We sought to determine if clinical decision support ( CDS ) embedded in an electronic health record ( EHR ) would improve clinician adherence to national asthma guidelines in the primary care setting . METHODS : We conducted a prospect i ve cluster-r and omized trial in 12 primary care sites over a 1-year period . Practice s were stratified for analysis according to whether the site was urban or suburban . Children aged 0 to 18 years with persistent asthma were identified by International Classification of Diseases , Ninth Revision codes for asthma . The 6 intervention- practice sites had CDS alerts imbedded in the EHR . Outcomes of interest were the proportion of children with at least 1 prescription for controller medication , an up-to- date asthma care plan , and the performance of office-based spirometry . RESULTS : Increases in the number of prescriptions for controller medications , over time , was 6 % greater ( P = .006 ) and 3 % greater for spirometry ( P = .04 ) in the intervention urban practice s. Filing an up-to- date asthma care plan improved 14 % ( P = .03 ) and spirometry improved 6 % ( P = .003 ) in the suburban practice s with the intervention . CONCLUSION : In our study , using a cluster-r and omized trial design , CDS in the EHR , at the point of care , improved clinician compliance with National Asthma Education Prevention Program guidelines Background Little is known about the impact of implementing nursing-oriented best practice guidelines on the delivery of patient care in either hospital or community setting s. Methods A naturalistic study with a prospect i ve , before and after design documented the implementation of six newly developed nursing best practice guidelines ( asthma , breastfeeding , delirium-dementia-depression ( DDD ) , foot complications in diabetes , smoking cessation and venous leg ulcers ) . Eleven health care organisations were selected for a one-year project . At each site , clinical re source nurses ( CRNs ) worked with managers and a multidisciplinary steering committee to conduct an environmental scan and develop an action plan of activities ( i.e. education sessions , policy review ) . Process and patient outcomes were assessed by chart audit ( n = 681 pre-implementation , 592 post-implementation ) . Outcomes were also assessed for four of six topics by in-hospital/home interviews ( n = 261 pre-implementation , 232 post-implementation ) and follow-up telephone interviews ( n = 152 pre , 121 post ) . Interviews were conducted with 83/95 ( 87 % ) CRN 's , nurses and administrators to describe recommendations selected , strategies used and participants ' perceived facilitators and barriers to guideline implementation . Results While statistically significant improvements in 5 % to 83 % of indicators were observed in each organization , more than 80 % of indicators for breastfeeding , DDD and smoking cessation did not change . Statistically significant improvements were found in > 50 % of indicators for asthma ( 52 % ) , diabetes foot care ( 83 % ) and venous leg ulcers ( 60 % ) . Organizations with > 50 % improvements reported two unique implementation strategies which included h and s-on skill practice sessions for nurses and the development of new patient education material s. Key facilitators for all organizations included education sessions as well as support from champions and managers while key barriers were lack of time , workload pressure and staff resistance . Conclusion Implementation of nursing best practice guidelines can result in improved practice and patient outcomes across diverse setting s yet many indicators remained unchanged . Mobilization of the nursing workforce to actively implement guidelines and to monitor the delivery of their care is important so that patients may learn about and receive recommended healthcare Objective . To evaluate effects on the process and outcomes of care brought about by use of a h and held , computer-based system that implements the American Academy of Pediatrics guideline on office management of asthma exacerbations . Design . A before – after trial with r and omly selected , office-based Connecticut pediatricians . In both the control and intervention phases , physicians collected data from 10 patient encounters for acute asthma exacerbations . During the intervention phase , the computer provided for structured encounter documentation and offered recommendations based on the guideline of the American Academy of Pediatrics . Patients were contacted by telephone 7 to 14 days after the visit to assess outcomes . Results . Nine study -physicians enrolled 91 patients in the control phase and 74 in the intervention phase . Follow-up information was available for 93 % of encounters . Use of the intervention was associated with increased mean frequency/visit of : 1 ) measurements of peak expiratory flow rate ( 2.18 vs 1.57 ) and oxygen saturation ( 1.12 vs .42 ) , and 2 ) administration of nebulized β2-agonists ( 1.25 vs .71 ) . Visits in the intervention phase lasted longer and fees were higher ( $ 145.61 vs $ 103.11 ) . There were no significant differences in immediate disposition or subsequent emergency department visits , hospitalizations , missed school , or caretaker 's missed work during the 7 days post visit . Conclusion . Use of h and held computers that provide guideline -based decision support was associated with increased physician adherence to guideline recommendations ; however , visits were prolonged , fees were higher , and no improvement could be demonstrated with regard to the observed intermediate-term patient outcomes . Guideline implementers ( and users ) should be cautious about putting unvali date d recommendations into practice INTRODUCTION Despite the frequency of acute asthma in the emergency department ( ED ) and the availability of guidelines , significant practice variation exists . Asthma care maps ( ACMs ) may st and ardize treatment . This study examined the use of an ACM to determine its effects on patient management in a regional hospital . METHODS Patients aged 2 to 65 years who presented to the ED with a primary diagnosis of acute asthma were enrolled in a prospect i ve study that took place 5 months before ( pre ) and 5 months after ( post ) ACM implementation . Research assistants using a st and ardized question naire abstract ed data through direct patient interviews and then followed up at 2 weeks with a st and ardized telephone interview . RESULTS Overall , 71 pre patients and 70 post patients were enrolled . Characteristics in both groups were similar . The care map was used in 100 % of the cases during the post period . The mean length of stay in the ED for the pre , compared with the post period , was similar ( 2 h 14 min v. 2 h 25 min ; p = 0.60 ) , as were admission rates ( 11 % v. 9 % ; p = 0.59 ) . Systemic corticosteroid use was similar ( 62 % v. 57 % ; p = 0.56 ) ; however , the total number of beta-agonists ( 2 v. 4 treatments ; p = 0.002 ) and anticholinergics ( 1 v. 2 treatments ; p < 0.001 ) administered in the ED was higher during the post period . Prescriptions for oral ( 73 % v. 60 % ; p = 0.15 ) and inhaled ( 78 % v. 78 % ; p = 0.98 ) corticosteroids at discharge remained the same . Relapse rates at follow-up were unchanged ( 29 % v. 34 % ; p = 0.52 ) . CONCLUSION This study provides evidence that implementation of an ACM increased acute bronchodilator use ; however , prescribing preventive medications did not increase . Further research is required to evaluate other strategies to improve asthma care by emergency physicians Background . Asthma , a leading chronic disease of children , currently affects about 6.2 million ( 8.5 % ) children in the United States . Despite advances in asthma research and availability of increasingly effective therapy , many children do not receive appropriate medications to control the disease , have overreliance on reliever medication , and lack systematic follow-up care . The situation is even worse for poor inner-city and minority children who have significantly worse asthma rates , severity , and outcomes . National Asthma Education and Prevention Program Guidelines recommend a multimodal , chronic care approach . Objective . The authors assessed the effectiveness of practice re design and computerized provider feedback in improving both practitioner adherence to National Asthma Education and Prevention Program Guidelines ( NAEPP ) , and patient outcomes in 295 poor minority children across four Federally Qualified Health Centers ( FQHC ) . Methods . In a nonr and omized , two-group ( intervention versus comparison ) , two-phase trial , all sites were provided re design support to provide quarterly well-asthma visits using structured visit forms , community health workers for outreach and follow-up , a Web-based disease registry for tracking and scheduling , and a provider education package . Intervention sites were given an additional Web-based , computerized patient-specific provider feedback system that produced a guideline -driven medication assessment prompt . Results . Logistic regression results showed that providers at intervention sites were more than twice as likely on average to prescribe guideline -appropriate medications after exposure to our feedback system during the Phase I enrollment period than providers at comparison sites ( exp(B ) = 2.351 , confidence interval [ CI ] = 1.315–4.204 ) . In Phase II ( the postenrollment visit period ) , hierarchical linear models ( HLMs ) and latent growth curves were used to show that asthma control improved significantly by .19 ( SE = .05 ) on average for each of the remaining four visits ( about 11 % of a st and ard deviation ) , and improved even more for patients at intervention sites . These results show that implementation of practice re design support guided by a pediatric chronic care model can improve provider adherence to treatment guidelines as well as patients ’ asthma control . Conclusions . The addition of patient-specific feedback for providers results in quicker adoption of guideline recommendations and potentially greater improvements in asthma control compared to the basic practice re design support alone PURPOSE Acute asthma is a common emergency department ( ED ) presentation and variation in its management is well recognized . The present study examined the use of an asthma care map ( ACM ) in one Canadian ED to improve adherence to acute asthma guidelines , emphasizing the use of systemic corticosteroids ( SCSs ) and inhaled corticosteroids ( ICSs ) . METHODS Three time periods were studied : the 15 months before ACM introduction ( PRE ) , the 15 months following a three-month introduction of the ACM ( POST(1 ) ) and the 18 months after POST(1 ) ( POST(2 ) ) . R and omly selected patient charts from each period were included from patients who were 18 to 60 years of age and presented with a primary diagnosis of acute asthma . A priori criteria were established to determine the degree of completion and success of the ACM . Primary outcomes included documentation , use of SCSs in the ED , and prescription of SCSs and ICSs at ED discharge . RESULTS A total of 387 patient charts were included ( PRE , n=150 ; POST(1 ) , n=150 ; POST(2 ) , n=87 ) . Patient characteristics in the three groups were similar ; however , patients in POST(1 ) and POST(2 ) showed higher use of newer agents than those in the PRE group . Overall , more women ( n=209 ; 54 % ) than men were seen ; the mean age was 32.4 years . The care map was used in 67 % of cases during POST(1 ) and 70 % during POST(2 ) . The use of peak expiratory flow ( PEF ) was high during the PRE , POST(1 ) and POST(2 ) periods ( 91 % , 89 % and 91 % , respectively ) ; however , documentation of other markers of severity increased in the POST periods . Use of SCSs occurred earlier ( P<0.01 ) and more often ( 57 % PRE , 68 % POST(1 ) and 75 % POST(2 ) ; P<0.01 ) in the POST(1,2 ) periods than the PRE period . There was a significant increase in use of SCSs on discharge ( 55 % PRE , 66 % POST(1 ) and 69 % POST(2 ) ; P<0.05 ) , and prescription of ICSs significantly increased ( 24 % PRE , 45 % POST(1 ) and 61 % POST(2 ) ; P<0.001 ) in the POST(1,2 ) periods . Discharge without any corticosteroids decreased over the three periods ( 32 % PRE , 21 % POST(1 ) and 17 % POST(2 ) ; P<0.05 ) . The length of stay in the ED increased over the study periods ( 181 min PRE , 209 min POST(1 ) and 265 min POST(2 ) ; P<0.01 ) and admissions were infrequent ( 9 % PRE , 13 % POST(1 ) and 6 % POST(2 ) ; P=0.50 ) . CONCLUSIONS The present study provides evidence that the st and ardized ED ACM was widely accepted , improved chart documentation , improved some aspects of ED care and increased prescribing of discharge preventive medications OBJECTIVE --To assess the effect of a preprinted form on the documentation of clinical data and compliance with the national guidelines for the management of asthma . METHODS -- Prospect i ve audit six months before and after introduction of the form . RESULTS --Use of the form improved the documentation of past asthma history ( 69 % v 93 % , P < 0.001 ) , current treatment ( 81 % v 95 % , P < 0.01 ) , predicted peak flow ( 23 % v 75 % , P < 0.001 ) , per cent predicted peak flow ( 1 % v 62 % , P < 0.001 ) , and respiratory rate ( 81 % v 95 % , P = 0.007 ) . Compliance with the British recommendations for treatment improved with use of the form ( 50 % v 89 % , P < 0.001 ) The prescription of steroids on discharge did not improve significantly ( 26 % v 44 % , P > 0.05 ) . CONCLUSIONS --The preprinted form result ed in enhanced documentation of data and conformity with current guidelines for the management of asthma Abstract Objective : To determine whether locally developed guidelines on asthma and diabetes disseminated through practice based education improve quality of care in non-training , inner city general practice s. Design : R and omised controlled trial with each practice receiving one set of guidelines but providing data on the management of both conditions . Subjects:24 inner city , non-training general practice s. Setting : East London . Main outcome measures : Recording of key variables in patient records ( asthma : peak flow rate , review of inhaler technique , review of asthma symptoms , prophylaxis , occupation , and smoking habit ; diabetes : blood glucose concentration , glycaemic control , funduscopy , feet examination , weight , and smoking habit ) ; size of practice disease registers ; prescribing in asthma ; and use of structured consultation “ prompts . ” Results : In practice s receiving diabetes guidelines , significant improvements in recording were seen for all seven diabetes variables . Both groups of practice s showed improved recording of review of inhaler technique , smoking habit , and review of asthma symptoms . In practice s receiving asthma guidelines , further improvement was seen only in recording of review of inhaler technique and quality of prescribing in asthma . Sizes of disease registers were unchanged . The use of structured prompts was associated with improved recording of four of seven variables on diabetes and all six variables on asthma . Conclusions : Local guidelines disseminated via practice based education improve the management of diabetes and possibly of asthma in inner city , non-training practice s. The use of simple prompts may enhance this improvement OBJECTIVE To determine the effect of an ED nurse-initiated asthma management protocol on door to first salbutamol nebulization time . METHODS This was a prospect i ve before-after study . Asthmatics , aged 1 to 12 years presenting to the ED with an exacerbation during the pre and post nurse-initiated care phases ( from 1/22/08 to 2/8/08 and from 2/12/08 to 3/4/08 ) , were eligible . An asthma training program was administered to nurses prior to post phase . Respiratory therapists started the first nebulization after a physician order during the pre phase , whereas bedside nurses initiated it before physician evaluation during the post phase . Mean differences and confidence intervals ( CI ) were calculated . RESULTS Each of the study groups had 125 patients . Door to first nebulization time was reduced by a mean of 31.3 minutes ( CI 23.0 , 39.6 ) in the post phase . Door to steroids , second nebulization , and bedside nurse evaluation time intervals were reduced by 22.8 minutes ( CI 8.8 , 36.9 ) , 21.7 minutes ( CI 9.1 , 34.4 ) and 15.6 minutes ( CI 7.5 , 23.7 ) respectively . CONCLUSION An ED nurse-initiated asthma management protocol expedited initiation of medications essential for relief of symptoms of acute asthma and bedside evaluation by nurses . St and ing nurse-initiated care protocol s may prove to be beneficial in improving acute asthma care in crowded EDs BACKGROUND In July 1996 , the New York City ( NYC ) regional EMS implemented a new protocol whereby EMS personnel in the prehospital setting could administer 125 mg of intravenous methyl prednisolone to asthma patients as one of their medical options following telephone consultation with a medical control physician . OBJECTIVE To determine whether this protocol had any effect on hospital admission rates or the emergency department ( ED ) length of stay . METHODS This retrospective chart review focused on the 219 ( of 603 total ) patients who arrived to the ED by ambulance over a two-year period whose ED diagnosis was asthma . There were 81 patient encounters in year 1 , and 138 in year 2 . Eleven of the year 2 group received prehospital steroids . The study took place at an urban 911 receiving , Level 2 ED . RESULTS Of the group who received prehospital steroids , none result ed in hospital admission . Due to the small sample size in the steroid-receiving group , the differences in these admission rates are not yet significant . No differences were detected in the ED length of stay between the two patient groups ( 157 vs. 160 minutes in year 2 , p = 0.9 ) . CONCLUSION The differences in admission rates suggested by this study suggest a simple yet potentially powerful tool for improving patient outcome in the treatment of asthma UNLABELLED BACKGROUND AND AIMS OF STUDY : All current international practice guidelines recommend that treatment of acute asthma in the emergency room ( ER ) should be guided by the peak expiratory flow rate ( PEFR ) . The aim of this study was to assess the efficacy of a PEFR guided protocol in treating ER asthma . METHODS We compared two different management protocol s in adult asthmatics who presented to the ER with acute exacerbations . The routine protocol ( RP ) assessed and dispensed patients according to overall subjective and clinical response without predetermined criteria . The peak protocol ( PP ) used serial measurements of PEFR to guide intensity of bronchodilator treatment and fitness for hospital discharge . On the PP , a threshold PEFR of > or = 60 % predicted had to be achieved before the patient could be discharged from the ER . RESULTS There were 79 patients in the RP group and 70 in the PP group . There was no significant difference between the two groups in baseline PEFR , PEFR after treatment and percentage increase in PEFR with treatment . The PP result ed in a higher hospital admission rate than RP . CONCLUSION We conclude that in the management of acute asthma in the ER , a PEFR guided protocol neither improved overall PEFR response to treatment nor reduced admission rates when compared with current management as it is practised in Singapore OBJECTIVES To assess whether a simple protocol used in the outpatient 's asthma clinic was effective in reducing emergency room ( ER ) visits and hospitalizations in chronic asthmatics during a year of follow-up , and to evaluate which type of asthmatics , according to severity of asthma , may benefit more from the protocol . METHODS Prospect i ve assessment of a simple protocol ( consisted of combined medical and educational aspects in the form of corticosteroids inhalation as a monotherapy and correction of the pitfalls of inhalation technique ) in reducing ER visits , and hospitalization in chronic asthmatics . It was performed in the out patients asthma clinic at King Abdul-Aziz University Hospital , Jeddah , Kingdom of Saudi Arabia . A total of 128 chronic asthmatics were evaluated and followed up for one year between January 1999 and March 2000 . RESULTS Between January 1999 and March 2000 the total number of ER visits , and hospitalizations in 128 chronic asthmatics in the year before the protocol were 269 and 85 . This was reduced to 116 ER visits and 27 hospitalizations a year after the protocol , a 55.4 % , and 68.2 % reduction . While only 25 % never attended ER before the protocol , almost 58.6 % did not attend ER after the protocol . The proportion that visited ER more frequently ( at least 3 times/year ) decreased from 50.8 - 18 % , a 65 % reduction . Similarly , patients who did not require hospitalization increased from 62.5 % up to 85.2 % . Moreover , the proportion that was hospitalized more frequently ( at least 3 times/year ) decreased from 10.2 % to as low as 0.8 % . Mean paired differences for ER visits were -1.16 1.42 with 95 % confidence interval extending from -1.412 to - 0.916 with a P value < 0.001 . Mean paired differences for hospitalization were -0.453 0.955 with 95 % confidence interval extending from -0.620 to -0.286 with a P value < 0.001 . CONCLUSION A simple protocol in outpatient 's asthma clinic can significantly reduce ER visits and hospitalizations in chronic asthmatics . All asthmatics , irrespective of severity benefited significantly from the protocol Rationale and aims Quality circles ( QCs ) are well established as a means of aiding doctors . New quality improvement strategies include benchmarking activities . The aim of this paper was to evaluate the efficacy of QCs for asthma care working either with general feedback or with an open benchmark . Methods Twelve QCs , involving 96 general practitioners , were organized in a r and omized controlled trial . Six worked with traditional anonymous feedback and six with an open benchmark ; both had guided discussion from a trained moderator . Forty-three primary care practice s agreed to give out question naires to patients to evaluate the efficacy of QCs . Results A total of 256 patients participated in the survey , of whom 185 ( 72.3 % ) responded to the follow-up 1 year later . Use of inhaled steroids at baseline was high ( 69 % ) and self-management low ( asthma education 27 % , individual emergency plan 8 % , and peak flow meter at home 21 % ) . Guideline adherence in drug treatment increased ( P = 0.19 ) , and asthma steps improved ( P = 0.02 ) . Delivery of individual emergency plans increased ( P = 0.008 ) , and unscheduled emergency visits decreased ( P = 0.064 ) . There was no change in asthma education and peak flow meter usage . High medication guideline adherence was associated with reduced emergency visits ( OR 0.24 ; 95 % CI 0.07–0.89 ) . Use of theophylline was associated with hospitalization ( OR 7.1 ; 95 % CI 1.5–34.3 ) and emergency visits ( OR 4.9 ; 95 % CI 1.6–14.7 ) . There was no difference between traditional and benchmarking QCs . Conclusions Quality circles working with individualized feedback are effective at improving asthma care . The trial may have been underpowered to detect specific benchmarking effects . Further research is necessary to evaluate strategies for improving the self-management of asthma patients OBJECTIVE To test the ability of an assessment -driven algorithm for treatment of pediatric status asthmaticus to reduce length and cost of hospitalization . DESIGN Nonr and omized , prospect i ve , controlled trial . SETTING Tertiary care children 's hospital . PATIENTS Children aged 1 to 18 years hospitalized for status asthmaticus ; 104 were treated using the asthma care algorithm ( intervention ) and 97 using unstructured st and ard treatment ( control ) . INTERVENTION Patients were treated using either an assessment -based algorithm or st and ard care practice s. The algorithm group was treated with st and ard medications ( aerosolized albuterol , systemic corticosteroids , epinephrine , ipratropium ) administered at a frequency driven by the patient 's clinical condition . Specific criteria were outlined for decreasing or augmenting therapy , transferring to intensive care , and discharging to home . A unique patient record containing assessment s , algorithm cues , and a treatment record was used . Intervention group patients were interviewed by telephone 1 week after discharge . MAIN OUTCOME MEASURES Hospital length of stay , cost per hospitalization , relapse rate , protocol adherence . RESULTS Average hospital stay for intervention patients was significantly shorter than for control patients ( 2.0 vs 2.9 days , P<.001 ) . Although intervention patients received fewer aerosolized albuterol doses than controls , there was no difference in short-term relapse rate between groups . The intervention saved more than $ 700 per patient in hospital charges . Adherence to the protocol was excellent , with only 8 variances per patient stay out of more than 150 opportunities . CONCLUSION An intensive , assessment -driven algorithm for pediatric status asthmaticus significantly reduces hospital length of stay and costs without increasing morbidity BACKGROUND The Canadian Clinical Practice Guidelines ( CPGs ) for the management of asthmatic patients were last published in 1999 , with up date s in 2001 and June 2004 . Large disparities exist in the implementation of these guidelines into clinical practice . OBJECTIVE The present study evaluated the knowledge of Quebec-based primary care physicians regarding the CPGs , as well as patient outcomes before and after introducing physicians to a new clinical tool -- a memory aid in the form of a self-inking paper stamp checklist summarizing CPG criteria and guidelines for assessing asthmatic patient control and therapy . The primary objective of the present study was to assess whether the stamp would improve physicians ' knowledge of the CPGs , and as a secondary objective , to assess whether it would decrease patient emergency room visits and hospitalizations . METHODS A prospect i ve , r and omized , controlled study of 104 primary care physicians located in four Quebec regions was conducted . Each physician initially responded to questions on their knowledge of the CPGs , and was then r and omly assigned to one of four groups that received information about the CPGs while implementing an intervention ( the stamp tool ) aim ed at supporting their decision-making process at the point of care . Six months later , the physicians were retested , and patient outcomes for approximately one year were obtained from the Régie de l'assurance maladie du Québec . RESULTS The stamp significantly improved physicians ' knowledge of the CPGs in all Quebec regions tested , and reduced emergency room visits and hospitalizations in patients who were followed for at least one year . CONCLUSION A paper stamp summarizing CPGs for asthma can be used effectively to increase the knowledge of physicians and to positively affect patient outcomes Fewer than 10 % of children with moderate or severe asthma receive an annual influenza vaccination despite their heightened susceptibility to severe infections and recommendations by the American Academy of Pediatrics and the Immunization Practice s Advisory Committee that all such children be vaccinated annually . Patient , provider , and system factors leading to this poor vaccination rate are not well understood . This study tested the effectiveness of a computerized reminder system in improving influenza vaccination rates in children with asthma and examined patient barriers to vaccination at one pediatric clinic in an urban teaching hospital . A computer data base identified 124 children with moderate or severe asthma . Patients were r and omly assigned either to study group ( n = 63 ) , who were sent a personalized letter reminder about the need for an influenza vaccination , or to a control group ( n = 61 ) , who received no reminder . Study group mothers were interviewed 2 months after the letter was sent to assess factors associated with receipt of vaccination , including demographic features , parental worry about asthma and vaccine side effects , the four dimensions of the Health Belief Model , and health locus of control beliefs . Nineteen study group patients ( 30 % ) received an influenza vaccination , compared with only 4 control patients ( 7 % ) ( P < .01 ) . Forty-three mothers of children in the study group were interviewed ; 14 ( 33 % ) of these children had received the vaccination . Of the characteristics investigated , two significantly correlated with vaccination compliance : high levels of parental worry about asthma ( positively correlated : odds ratio = 23.3 , P < .01 ) and high levels of parental worry about vaccine side effects ( negatively correlated : odds ratio = 0.087 , P = .025 ) . ( ABSTRACT TRUNCATED AT 250 WORDS INTRODUCTION To determine if an evidence -based implementation ( EBI ) could lead to the successful implementation of evidence based care for adult asthma in small rural district hospitals . METHODS A controlled trial involving eight small rural hospitals ( four each in the study and control groups ) was conducted . Retrospective pre-intervention audits were conducted at all eight hospitals for 7 months ( 1 January 2004 to 31 July 2004 ) and evidence - practice gaps identified . An EBI was then used to implement established guidelines for the management of asthma in the study hospitals . Post-intervention audits were then performed over a period of 7 months ( 1 October 2004 to 31 April 2005 ) . RESULTS There were 52 presentations of asthma in the study hospitals in the pre-implementation phase and 47 post-implementation . The corresponding numbers for the control hospitals were 46 and 42 respectively . There were no statistically significant differences in the severity between the groups . Following the EBI there were significant improvements at the study hospitals for the documentation of severity ( 8 % to 62 % , p < 0.001 ) , use of spirometry ( 12 % to 62 % , p < 0.001 ) and the use of written short-term asthma plans ( 9 % to 26 % , p = 0.05 ) . There was a decrease in use of ipratropium in mild asthma ( 44 % to 30 % , p = 0.228 ) , an increase in the use of systemic steroids ( 61 % to 72 % , p = 0.255 ) and no change in prescribing antibiotics for afebrile patients with asthma ( 21 % to 21 % p = 0.956 ) . There was no significant change in practice at the control hospitals except for a decrease in the use of systemic steroids ( 48 % to 21 % , p = 0.011 ) . For the six clinical indicators aggregate there was a significant increase in compliance with guidelines at the study hospitals ( 36 % to 62 % , p < 0.001 ) but no change at the control hospitals ( 31 % to 31 % , p = 0.970 ) . CONCLUSION The pre-intervention audits demonstrated low levels of compliance with asthma guidelines across six clinical indicators . An EBI significantly improved compliance across these six indicators , and no improvement was noted in the control hospitals . This study demonstrates that an EBI can alter clinical practice in small rural district hospitals 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 Aim : To determine the effect of implementing a clinical pathway , using evidence -based clinical practice guidelines , for the emergency care of children and adolescents with asthma . Methods : A prospect i ve , before – after , controlled trial was conducted , which included patients aged 1–18 years who had acute exacerbations of asthma treated in a tertiary care paediatric emergency department . Data were collected for identical 2-month seasonal periods before and after implementation of the clinical pathway to determine hospitalisation rate and other outcomes . For 2 weeks after emergency visits , the rate at which patients returned to emergency care for worsening asthma was evaluated . A multidisciplinary panel , using national guidelines and a systematic review , developed the pathway . Results : 267 patients were studied . The rate of hospitalisation was significantly lower in the post-implementation group ( 10/74 ; 13.5 % ) than in the pre-implementation control group ( 53/193 ; 27.5 % ; p = 0.02 ; number needed to treat 7.1 ) . All reduction in hospitalisation occurred in children with moderate to severe asthma exacerbation . After implementation of the clinical pathway , the rate of administration of oral corticosteroids to patients with moderate or severe exacerbations increased from 71 % to 92 % ( p = 0.01 ) , and significantly more patients received β2-agonists in the first hour ( p = 0.02 ) . No significant change in relapse to acute care occurred within 2 weeks ( p = 0.19 ) . Conclusions : An evidence -based clinical pathway for children and adolescents with moderate to severe exacerbations of acute asthma markedly decreases their rate of hospitalisation without increased return to emergency care OBJECTIVE It is difficult to control drug-prescribing behaviour in general practice , despite the development and distribution of guidelines . The purpose of this study was to assess the effect on drug-prescribing behaviour of implementing prescribing guidelines by means of a reactive computer reminder system ( CRS ) . DESIGN Cluster-r and omised controlled trial with an incomplete block design in the south of the Netherl and s : 25 GPs ( 7 GP practice s ) received reminders about antibiotics and asthma/ COPD prescriptions , 28 GPs ( 7 GP practice s ) received reminders about cholesterol prescriptions . Prescription guidelines were integrated into the computerised GP information system . MEASUREMENTS Both performance indicators and prescription volumes were calculated as the main outcome measures . Next to individual volume measure , sum scores were constructed on the volume measures per drug group ( antibiotics , asthma/ COPD and cholesterol ) . RESULTS Variation between GPs turned out to be larger and more skewed than expected . No differences between groups were found for indicators and volumes related to recommendations advocating certain drugs . Although there was a tendency towards clinical ly relevant results for prescription volumes that were supposed to drop , the difference in sum score between the groups was not significant . For antibiotic prescriptions that were supposed to drop , the sum score for the intervention group was 28.2 ( 95 % CI : 20.8 - 44.5 ) prescriptions per 1000 patients per GP , while this was 39.7 ( 95 % CI : 29.7 - 64.1 ) for the control group ( p 0.2 ) . For prescriptions asthma/ COPD that were supposed to drop , the sum score for the intervention group was 1.1 ( 95 % CI : 0.6 - 2.6 ) prescriptions per 1000 patients per GP , while this was 2.2 ( 95 % CI : 1.4 - 4.3 ) for the control group ( p 0.1 ) . On three specific recommendations ( on quinolones for cystitis , corticosteroids for CPOD , and antibiotics for acute sore throat ) significant differences were found . CONCLUSIONS This study turned out to be underpowered due to high inter doctor variation in prescribing behaviour . Nevertheless , computerised reminders sometimes have a favourable effect on restricting certain drugs that are not or no longer indicated in general practice This study sought to determine if a clinical pathway developed and executed by specialists in pediatric asthma would reduce hospital costs and length of stay ( LOS ) . The study design was a retrospective , nonr and omized , controlled trial . Subjects were children aged 2 - 18 years ( N = 1,004 ) with a history of recurrent wheezing , hospitalized with a diagnosis of acute asthma exacerbation between 1995 - 1998 at the New York Hospital-Weill Cornell Medical Center and treated via the pathway , as well as a control group of 206 children ages 2 - 18 hospitalized for acute asthma exacerbation in 1994 , the year prior to pathway implementation . Patients were treated via the pathway under the supervision of an asthma specialist . The pathway provided guidelines for : 1 ) frequency of patient assessment ; 2 ) bronchodilator usage ; 3 ) corticosteroid use ; 4 ) laboratory evaluation ; 5 ) vital signs , oxygen saturation , and peak flow measurements ; 6 ) chest x-rays ; 7 ) social work intervention ; and 8) discharge planning . The main outcome measures were hospital length of stay , cost per hospitalization , nursing , medication , laboratory and radiology costs , and relapse rate . Total charges for admission and average LOS for 1995 - 1998 were calculated , and compared with 1994 , the year preceding implementation of the pathway . LOS decreased from 4.2 days to 2.7 days ( P < 0.0001 ) . The annual total charges for pediatric asthma admissions decreased from 2 million dollars to 1.4 million dollars ( P < 0.005 ) . Nursing and laboratory costs showed a statistically significant decrease . Follow-up study at 8 months showed a readmission rate of 0.02 % . The implementation of a pediatric asthma clinical pathway , directed by specialists , result ed in significantly decreased length of stay and overall cost , without an increased rate of readmission There is a wide variability in clinical practice for treating acute asthma ( AA ) in the emergency department ( ED ) , interfering in the quality of care . The purpose of this study was to evaluate the impact of a clinical pathway on the management of AA in the ED . We conducted a prospect i ve before-after study of patients presenting with AA to the adult ED , during five separate periods ( from January to March ) : in 2001 ( pre- protocol group ) , 2002 , 2003 , 2004 , and 2005 ( 6 months without educational reinforcement ) . We evaluated the effects of the recommendations on objective assessment of severity , diagnostic re source utilization , use of recommended and non-recommended therapy , and outcomes . The 2001 , 2002 , 2003 , 2004 , and 2005 groups comprised , respectively : 108 , 96 , 97 , 98 , and 101 patients . There was a significant increase in the use of pulse oximetry ( 8.3 % , 77.1 % , 88.7 % , 95.9 % , and 97.0 % , respectively ; p < 0.001 ) . There was an increase in the use of peak expiratory flow rate from 2001 to 2004 ( 4.6 % , 20.8 % , 28.9 % , and 48.0 % ) and a decrease after a period without educational efforts ( 29.7 % , p < 0.001 ) . Although the overall use of systemic corticosteroids was not changed , there was a significant increase in the use of oral steroids ( p < 0.001 ) . There was a decrease in aminophylline utilization ( p = 0.005 ) . Length of stay in the ED was significantly reduced ( p = 0.04 ) . There was no effect on hospital admission or emergency discharge ( p = 0.193 ) . The AA clinical pathway applied in the ED was associated with a positive effect on improving the quality of care There is no consensus on the optimal length of stay and timing of release from hospital in patients admitted with acute asthma . We hypothesize that it might be safe to discharge patients from hospital once they have responded clinical ly to intensive anti-asthma treatment . In a non-r and omized prospect i ve controlled study , we compared two discharge protocol s in consecutive patients admitted for acute severe exacerbations of bronchial asthma . Patients in group A were discharged after remission of signs and symptoms and those in group B after improvement but before complete remission of signs and symptoms . Peak expiratory flow rates ( PEFR ) were monitored but were not used as discharge criteria for either group . Patients with complicating disease and who were likely to be non-compliant were excluded . The length of hospital stay ( LOS ) and best PEFR at discharge were significantly lower in group B ( 87 admissions ) than group A ( 80 admissions ) . The mean ( + /-SD ) LOS was 1.8(+/- 1 ) days vs. 3.5(+/- 1.4 ) days and best PEFR was 58(+/- 17)% predicted versus 71(+/- 15)% predicted respectively ( P < 0.001 for both variables ) . No patient in either group relapsed within 4 weeks of discharge from hospital . We concluded that the release of asthmatics who respond promptly to intensive treatment and are compliant with medication despite incomplete resolution of symptoms , signs and PEFR at the time of discharge from hospital may not be associated with increased risk of early relapse BACKGROUND AND OBJECTIVES This project focused on increasing compliance , in a large family practice group , with quality indicators for the management of asthma . The objective was to determine if use of a flow sheet incorporating the Global Initiative for Asthma ( GINA ) guidelines could improve compliance with those guidelines if the flow sheet was placed in patients ' medical records . METHODS After review and selection of 14 clinical quality indicators , physicians in the practice implemented a flow sheet as an intervention . These flow sheets were inserted into the records of 122 r and omly selected patients with asthma . Medical records were review ed before the flow sheets were placed in the records , and again approximately 6 months later , to determine if there was a change in compliance with the quality indicators . RESULTS Improvement of documentation was demonstrated in 13 of the 14 quality indicators . CONCLUSIONS The results indicate that compliance with asthma management quality indicators can improve with the use of a flow sheet The objective of our study was to compare the safety and efficacy of discharging asthmatic children from hospital on three versus four hourly nebulized salbutamol . The setting was a tertiary referral paediatric hospital in Sydney , NSW , Australia . The design was a r and omized controlled parallel group study . All children admitted to hospital with acute asthma and who were over 18 months of age were eligible to enter the study . Patients were excluded if they had non-English speaking parents , no telephone , or chronic cardiac or neurological disease . Children were treated according to st and ard asthma management but were r and omly allocated to be discharged on three or four hourly nebulized salbutamol . Patients were surveyed using a telephone question naire 1 to 2 weeks after discharge . The primary outcome measure was re-presentation to the Emergency Department ( ED ) within 7 days . Other outcomes included readmission to hospital , re-presentation to the local doctor , parental satisfaction and length of hospital stay . A total of 63 children were enrolled in the study ( 32 in the three hourly group and 31 in the four hourly group ) . There were no re-presentations to the ED or hospital readmissions within 1 to 2 weeks in either group . However , re-presentations to the local doctor were common , 71.8 % in the three hourly and 74.1 % in the four hourly groups , respectively . These were predominantly for routine review . The mean ( + /- SD ) hospital length of stay was not significantly different between the three and four hourly groups , 48.94 ( + /- 20.61 ) and 54.88 ( + /- 32.59 ) hours , respectively ( P = 0.672 ) . Parents felt the timing of discharge was ' too early ' in five ( 15.6 % ) of three hourly and five ( 16.1 % ) of four hourly patients . Three ( 9.7 % ) of the four hourly but none of the three hourly patients felt they were sent home ' later than necessary ' . Five ( 15.1 % ) of the three hourly and three ( 9.7 % ) of the four hourly group parents did not feel comfortable looking after their child at home immediately after discharge . None of these differences were statistically significant . Discharge of asthmatic children from hospital on three hourly nebulized salbutamol is as safe and effective as on four hourly . Parents are generally very satisfied with timing of discharge , irrespective of frequency of nebulization . Earlier discharge benefits both the child and their family , and improves hospital bed utilization BACKGROUND Although asthma clinical pathways are used with increasing frequency , few controlled studies have evaluated the clinical and cost effectiveness of these pathways . OBJECTIVE To evaluate the effect of an inpatient asthma clinical pathway on cost and quality of care for children with asthma . METHODS One hundred forty-nine children were treated for status asthmaticus using an asthma clinical pathway in a children 's hospital between September and December 1997 . Thirty-four of 149 children treated with the clinical pathway were r and omly selected . A retrospective cohort control group of non-pathway patients ( N = 34 ) was matched with each pathway patient by age , race , gender , co-morbidities , asthma severity score , ICU admission , and time of year admitted . Differences between the two groups in length of stay , total costs , readmission rate , inpatient management , and discharge medications were compared . RESULTS Length of stay was significantly lower in the clinical pathway group compared with the control group ( 36 hours versus 71 hours , P < .001 ) and total costs decreased significantly ( $ 1685 versus $ 2829 , P < .001 ) as a result of the pathway . Asthmatic children on the clinical pathway were significantly more likely than the control group to complete asthma teaching while hospitalized ( 65 % versus 18 % , P < .001 ) , to be discharged with a prescription for a controller medication ( 88 % versus 53 % , P < .01 ) , and to have a peak flow meter ( 57 % versus 23 % , P < .05 ) and a spacer device ( 100 % versus 71 % , P < .001 ) for home use . CONCLUSION Implementation of this inpatient clinical pathway led to a decrease in length of stay and a reduction in total cost while improving quality of care for hospitalized asthmatic children OBJECTIVE To improve health outcomes of children and adolescents with asthma using a multifaceted intervention for GPs . METHODS The design of the study was a cluster r and omized controlled trial . GPs were r and omized at a practice level in general practice clinics in Melbourne , Australia . Participants were children/adolescents aged 2 - 14 years with asthma and their caregivers identified from the medical records of participating clinics . Question naires were completed by 411 at baseline and 341 at follow-up . The intervention arm ( n = 18 GPs ) participated in a small group asthma education programme and was provided with locally adapted paediatric asthma guidelines . One control arm ( n = 18 GPs ) received only the adapted paediatric asthma guidelines , while the other control arm ( n = 15 GPs ) received an unrelated educational intervention . The outcome measures of the study were children/adolescents and caregivers completed question naires about asthma management and control , asthma knowledge and quality of life at recruitment and 6 months later . Ownership of a written asthma action plan ( WAAP ) was the primary outcome . RESULTS There was no evidence for changes in ownership of WAAPs between the three study arms . Adolescents in the intervention group reported an improvement in quality of life subscale score ' positive effects ' ( mean difference = 2.64 , P = 0.01 ) , but there was no evidence for an effect of the intervention on other study outcomes among the three study arms . CONCLUSIONS The intervention was associated with some improvement in quality of life for adolescents . However , overall , the intervention did not translate into increased ownership of WAAPs , control of asthma or improved quality of life OBJECTIVE . The goal was to determine whether home asthma telemonitoring with store- and -forward technology improved outcomes , compared with in-person , office-based visits . METHODS . A total of 120 patients , 6 to 17 years of age , with persistent asthma were assigned r and omly to the office-based or virtual group . The 2 groups followed the same ambulatory clinical pathway for 12 months . Office-based group patients received traditional in-person education and case management . Virtual group patients received computers , Internet connections , and in-home , Internet-based case management and received education through the study Web site . Disease control outcome measures included quality of life , utilization of services , and symptom control . RESULTS . A total of 120 volunteers ( 45 female ) were enrolled . The groups were clinical ly comparable ( office-based : 22 female/38 male ; mean age : 9.0 ± 3.0 years ; virtual : 23 female/37 male ; mean age : 10.2 ± 3.1 years ) . Virtual patients had higher metered-dose inhaler with valved holding chamber technique scores than did the office-based group at 52 weeks ( 94 % vs 89 % ) , had greater adherence to daily asthma symptom diary su bmi ssion ( 35.4 % vs 20.8 % ) , had less participant time ( 636 vs 713 patient-months ) , and were older . Caregivers in both groups perceived an increase in quality of life and an increase in asthma knowledge scores from baseline . There were no other differences in therapeutic or disease control outcome measures . CONCLUSIONS . Virtual group patients achieved excellent asthma therapeutic and disease control outcomes . Compared with those who received st and ardized office-based care , they were more adherent to diary su bmi ssion and had better inhaler scores at 52 weeks . Store- and -forward telemedicine technology and case management provide additional tools to assist in the management of children with persistent asthma STUDY OBJECTIVE To determine the effect of a critical pathway on re source utilization in asthmatic patients . METHODS The study combined a prospect i ve analysis of 149 patients with asthma treated by a pathway protocol with a retrospective analysis of 97 patients with asthma treated by conventional means . The setting was a community hospital . RESULTS Among patients treated by protocol , oxygen use declined by 19 % ( P = .001 ) , h and held nebulizer treatments by 33 % ( P = .001 ) , saline locks by 15 % ( P = .011 ) , and intravenous steroid administration by 13 % ( P = .034 ) . There was an increase in the use of metered-dose inhalers with spacer by 64 % ( P = .001 ) and oral steroids by 18 % ( P = .027 ) . CONCLUSION A critical pathway , based primarily on national guidelines , can be an effective means of treating asthma patients in terms of re source utilization Background . Clinical pathways for asthma are tools that have the potential to improve compliance with nationally recognized management guidelines , but their effect on patient outcomes has not been documented . Objectives . To determine the effect of an asthma clinical pathway on patients ' length of stay , use of nebulized β-agonist therapy while hospitalized , and use of acute care clinics for 2 weeks after discharge . Design / Methods . The study was a r and omized , controlled trial . Patients between the ages of 2 and 18 years admitted with an asthma exacerbation and not under the care of an asthma specialist were eligible for the study . Patients were r and omized either to a conventional ward ( control group ) or to a ward using the clinical pathway ( intervention group ) . For 2 weeks after discharge , we collected data to determine whether patients visited a health care provider for worsening asthma . Results . One hundred ten patients ( 26 % ) were enrolled . Control and intervention groups had similar demographic and asthma severity profiles . The intervention group had an average length of stay 13 hours shorter than did the control group . In addition , at every dosing interval , the intervention group received less nebulized β-agonist therapy . There were no deaths in either group . Conclusion . A clinical pathway for inpatient asthma decreased the length of stay and β-agonist medication use with no adverse outcomes or increased acute-care encounters through 2 weeks after discharge PRIMARY OBJECTIVE To investigate whether computer decision support software used in the management of patients with asthma improves clinical outcomes . RESEARCH DESIGN R and omized controlled trial with practice s each reporting on 30 patients with asthma over a 6 month period . METHODS AND PROCEDURES 447 patients were r and omly selected from practice asthma registers managed by 17 general practice s from throughout the UK . Intervention practice s used the software during consultations with these patients throughout the study while control practice s did not . MAIN OUTCOMES AND RESULTS Practice consultations , acute exacerbations of asthma , hospital contacts , symptoms on assessment and medication use . A smaller proportion of patients within the intervention group initiated practice consultations for their asthma : 34 ( 22 % ) vs 111 ( 34 % ) , odds ratio ( OR ) = 0.59 , 95 % confidence interval ( CI ) ( 0.37 - 0.95 ) ; and suffered acute asthma exacerbations : 12 ( 8 % ) vs 57 ( 17 % ) , OR = 0.43 , 95 % CI = 0.21 - 0.85 six months after the introduction of the computer decision support software . There were no discernable differences in reported symptoms , maintenance prescribing or use of hospital services between the two groups . CONCLUSION The use of computer decision support software that implements guidelines during patient consultations may improve clinical outcomes for patients with asthma Aims : To evaluate the effect of the implementation of an asthma clinical pathway on asthma in children in general practice . Methods : A r and omized , controlled trial involving 270 general practitioners . One group of general practitioners implemented the asthma clinical pathway for children ( intervention group ) and the control group continued with their usual asthma medical care management . The main outcome measures were admissions to hospital for asthma and attendance at the Children 's Emergency Department . Compliance with the guidelines was assessed by examining asthma drug prescriptions . Results : Admissions to hospital for asthma dropped 40 % in the intervention group , by 33 % in the control group and by 22 % in general practitioners not participating in the trial . The differences between the intervention and control and between the intervention and non‐participating general practitioners were not statistically significant . The decrease in attendance at the Children 's Emergency Department decreased by 25 % , 30 % and 19 % , respectively , but this was not statistically significant . There was a significant decrease in prescriptions for oral relievers , dry powder relievers in the under 6s , mast cell stabilizers and methylxanthines in both control and intervention groups . However , only for oral relievers was there a significant difference between the intervention group and control , with the decrease larger in the intervention group ( p<0.001 ) OBJECTIVE To assess the impact of an asthma management program on the dispensing of inhaled corticosteroids , hospitalizations , and emergency department ( ED ) visits on children , adolescents , and young adults . DESIGN We used medical record and pharmacy data for the 18 months after initiation of a pilot asthma management program . Two intervention offices were matched with 2 control offices on pediatric volume , number of pediatricians or family practitioners , and specialist availability . SETTING Primary care offices at Kaiser Permanente Colorado , in Denver and Boulder . PATIENTS We identified 298 patients , 18 years or younger , who were listed in an asthma registry between February 1 and July 31 , 1997 , as having moderate or severe asthma . INTERVENTION The Kaiser Permanente Colorado Asthma Care Management Program is an outpatient-based program that provides comprehensive evaluation , education , and follow-up to patients identified from an asthma registry or referred by providers . MAIN OUTCOME MEASURES The proportion of patients who received more than 1 dispensing of inhaled corticosteroid during the observation period . Additional outcomes measured the proportion of patients with 1 or more hospitalizations or ED visits . RESULTS A significantly greater proportion of patients from the intervention group received more than 1 dispensing of inhaled corticosteroid compared with controls ( relative risk [ RR ] , 1.41 ; 95 % confidence interval [ CI ] , 1.08 - 1.72 ) . We found no significant difference in the proportion of patients who were hospitalized ( RR , 1.37 ; 95 % CI , 0.48 - 3.71 ) or visited the ED ( RR , 0.86 ; 95 % CI , 0.49 - 1.40 ) . CONCLUSIONS The presence of an asthma management program may improve dispensing of inhaled corticosteroids to young patients with moderate or severe asthma , as recommended by national guidelines . This type of program may not have an effect on hospitalizations or ED visits OBJECTIVE Translation of evidence -based guidelines into clinical practice has been inconsistent . We performed a r and omized , controlled trial of guideline -based care suggestions delivered to physicians when writing orders on computer workstations . STUDY SETTING Inner-city academic general internal medicine practice . STUDY DESIGN R and omized , controlled trial of 246 physicians ( 25 percent faculty general internists , 75 percent internal medicine residents ) and 20 outpatient pharmacists . We enrolled 706 of their primary care patients with asthma or chronic obstructive pulmonary disease . Care suggestions concerning drugs and monitoring were delivered to a r and om half of the physicians and pharmacists when writing orders or filling prescriptions using computer workstations . A 2 x 2 factorial r and omization of practice sessions and pharmacists result ed in four groups of patients : physician intervention , pharmacist intervention , both interventions , and controls . DATA EXTRACTION / COLLECTION METHODS : Adherence to the guidelines and clinical activity was assessed using patients ' electronic medical records . Health-related quality of life , medication adherence , and satisfaction with care were assessed using telephone question naires . PRINCIPAL FINDINGS During their year in the study , patients made an average of five scheduled primary care visits . There were no differences between groups in adherence to the care suggestions , generic or condition-specific quality of life , satisfaction with physicians or pharmacists , medication compliance , emergency department visits , or hospitalizations . Physicians receiving the intervention had significantly higher total health care costs . Physician attitudes toward guidelines were mixed . CONCLUSIONS Care suggestions shown to physicians and pharmacists on computer workstations had no effect on the delivery or outcomes of care for patients with reactive airways disease OBJECTIVE : The purpose of this study was to determine if a brief educational intervention ( INT ) on the treatment of acute asthma improved prescribing patterns of internal medicine residents in an emergency department ( ED ) . Additional objectives were to determine if optimal therapy reduced length of stay ( LOS ) in the ED and to determine if discharge prescribing patterns could be improved . DESIGN : Nonr and omized , single-blind INT study . SETTING : A large , urban , county-owned , university-affiliated ED . PATIENTS AND OTHER PARTICIPANTS : Eight internal medicine residents in each of three study periods ; numbers of adult asthmatics for each period were : control group , 129 ( Nov — Dec 1989 ) ; INT group A , 82 ( Jan — Feb 1990 ) ; and INT group B , 139 ( Nov — Dec 1990 ) . INTERVENTIONS : INT consisted of a ten-minute verbal presentation , a three-page summary of the literature , and a posted protocol in the ED . Control data were collected prior to any INT . Prescribing patterns were covertly evaluated in each of the three study periods . Because discharge prescribing of long-term antiinflammatory therapy with inhaled corticosteroids was not improved in group A , emphasis on this point was added for group B. MAIN OUTCOME MEASURES : Percentage of patients who received desired acute and discharge therapies and LOS for each study period . RESULTS : Increased prescribing of desired acute therapy in the ED was seen in both INT groups . For discharge prescribing , the INT was partially successful . Reduced LOS was not found for the INT groups . CONCLUSIONS : A brief INT effectively improves prescribing of optimal acute therapy of asthma in the ED , yet does not appear to reduce LOS . Further strategies are needed to impact on therapy prescribed at discharge from the ED The purpose of this study was to improve asthma care and outcome in an inner-city emergency department . Consecutive adult patients ( 19,802 ) presenting with the diagnosis of acute asthma exacerbation to an inner-city municipal hospital emergency department , between July 1991 and December 1993 , were prospect ively evaluated . These patients were compared to a historical control group of 7923 consecutive asthma emergency department patients presenting in the year prior to our intervention . An asthma treatment guideline was implemented through a continuous quality improvement process . Asthma relapse rate and admission rate were obtained before and after the guidelines were instituted . Data after interventions were also prospect ively compared to asthma outcomes at all other New York City municipal hospital emergency departments . After intervention , mean monthly asthma relapse rates showed a significant reduction from 12.18 % to 7.83 % ( p < 0.001 ) . A similar decrease was also noted in the monthly asthma admission rate , from 4.85 to 3.90 per 100 emergency department visits ( p < 0.05 ) . Asthma treatment guidelines along with continuous quality improvement techniques can significantly improve the outcome of inner-city emergency department asthma patients OBJECTIVE To determine whether clinician prompting regarding a child 's symptom severity and guideline recommendations at the time of an office visit improves the delivery of preventive asthma care . DESIGN R and omized controlled trial . SETTING Two inner-city pediatric practice s in Rochester , NY . PARTICIPANTS Two hundred twenty-six children with persistent asthma ( aged 2 - 12 years ) presenting to the clinics for well-child care , asthma care , or non-asthma-related illness care . Intervention We assigned children r and omly to a clinician-prompting group ( single-page prompt including the child 's symptoms and guideline recommendations given to the clinician at the time of the visit ) or a st and ard-care group ( no prompt given ) . Interviewers called parents after the visit to inquire about preventive measures taken , and medical charts were review ed . MAIN OUTCOME MEASURES Any preventive action related to asthma taken at the visit . RESULTS Children in the clinician-prompting group were more likely to have had any preventive measures taken at the visit compared with children in the st and ard-care group ( 87 % vs 69 % ) . Specifically , visits for children in the clinician-prompting group were more likely to include delivery of an action plan ( 50 % vs 24 % ) , discussion s regarding asthma ( 87 % vs 76 % ) , and recommendations for an asthma follow-up visit ( 54 % vs 37 % ) . In a regression model , children in the clinician-prompting group had 3-fold greater odds of receiving any preventive action compared with the st and ard-care group . CONCLUSION Clinician prompting regarding asthma severity and care guidelines at the time of an office visit significantly improved the delivery of preventive asthma care Objective : To evaluate the effectiveness of a tailored and multifaceted approach to the implementation of nationally recommended and evidence -based guidelines in primary care within existing systems and re sources . Methods : A non-r and omised Latin square to compare guideline implementation in two neighbouring health districts covering 180 general practice s. Evidence -based guidelines for the treatment of patients with asthma and angina were implemented actively in one district and passively disseminated in the other district . Outcome measures for asthma were smoking status and inhaler technique . For angina the outcome measures were : smoking status ; blood pressure ; aspirin prescribed , contraindicated or self-medicated ; beta-blocker prescribed or contraindicated ; routine hospital admission ; prescribed drugs ; self-reported change . Results : There were improvements in all outcome criteria between baseline and follow-up audits , regardless of whether the guideline was actively implemented or passively disseminated . The estimated increase in the proportion of records complying with guidelines was 4 % [ 95 % confidence intervals ( CI ) : 0 , 8 ] and was higher in intervention than in control practice s. Using only records not compliant at baseline , the corresponding difference was 15 % ( 95 % CI : 7 , 24 ) . The only significant improvement associated with active implementation was smoking status in angina patients . Both prescribing and hospital admission monthly totals changed during the period of the trial , but there was no significant difference between the pattern of changes in intervention and control districts . A significantly greater proportion of health professionals saw the intervention guideline compared with the control ( 75 % versus 25 % ) . There was a significant correlation between self-reported change and interventions steps ( P < 0.05 ) . Conclusions : Increases in quality markers occurred irrespective of the multifaceted implementation efforts . Some of this increase was due to the method of data collection . Nevertheless , national initiatives may have more influence than local implementation initiatives Summary Objective Asthma is the most common chronic disease in children . Previous studies described significant variations in acute asthma management in children . This study was conducted to examine whether asthma management in the pediatric emergency department ( ED ) was improved through the use of an evidence -based acute asthma care guideline reminder card . Methods The Pediatric Acute Asthma Management Guideline ( PAMG ) was introduced to the ED of a pediatric tertiary care hospital in Ontario , Canada . Medical charts of 278 retrospective ED visits ( January – December 2002 ) and 154 prospect i ve visits ( July 2003–June 2004 ) were review ed to assess changes in acute asthma management such as medication treatment , asthma education , and discharge planning . Logistic and linear regressions were used to determine the effect of PAMG on asthma management in the ED . The propensity score method was used to adjust for confounding . Results During the implementation of PAMG , patients who visited the ED were more likely to receive oral corticosteroids ( Adjusted Odds Ratio [ AOR ] = 2.26 , 95 % CI : 1.63–3.14 , p < 0.0001 ) and oxygen saturation re assessment before ED discharge ( AOR = 2.02 , 95 % CI : 1.45–2.82 , p < 0.0001 ) . They also received 0.23 ( 95 % CI : 0.03–0.44 , p = 0.0283 ) more doses of bronchodilator in the first hour of ED stay . Improvements in asthma education and discharge planning were noted , but the changes were not statistically significant . Conclusions After the implementation of an evidence -based guideline reminder card , medication treatment for acute asthma in the ED was significantly improved ; however , asthma education and discharge planning remained unchanged . Future efforts on promoting guideline -based practice in the ED should focus on these components OBJECTIVE To evaluate a project to implement guidelines on the management of patients with asthma or chronic obstructive pulmonany disease ( COPD ) in terms of the health outcomes of these patients . DESIGN A before- and -after study of 1 year with a non-r and omized but comparable reference group . SETTING General practice s in the Netherl and s. STUDY PARTICIPANTS Two-hundred and eighty patients from 14 practice s in the intervention group and 90 patients from five practice s in the reference group ( receiving usual care ) . INTERVENTION The project included a comprehensive implementation programme , involving identification of barriers , documentation of the care provided , specific education , feedback on compliance with the guidelines , and peer review . This project has been found to bring the process of care more in agreement with the guidelines . MAIN OUTCOME MEASURES Mean peak expiratory flow rate ( PEFR ) as a percentage of the predicted value , number of days with a diurnal variation in PEFR > or = 15 % , number of days with respiratory symptoms ( all recorded by patients for a period of 14 days ) , and perceived health status ( Nottingham Health Profile ) . RESULTS After 1 year , the intervention group showed statistically significant improvements with regard to the mean PEFR , the diurnal variation in PEFR , respiratory symptoms and the pain score of the Nottingham Health Profile . Comparing the changes within the intervention group with the changes within the reference group , only a positive effect of the intervention on the mean PEFR was found . CONCLUSION The comprehensive implementation programme improved the lung function and symptoms of asthma and COPD patients in the intervention group . However , in comparison with a reference group , the positive effect on the lung function was only small OBJECTIVE To determine whether an integrated care pathway ( ICP ) could improve care delivered to patients coming to an emergency department only or to patients who were subsequently admitted . STUDY DESIGN Children ( age , 2 - 16 years ; n = 298 ) coming to the ED with acute asthma/wheeze , were r and omized by using a cluster design to either st and ard care or care delivered by an ICP . RESULTS Children discharged from the ED who received care with an ICP ( n = 118 ) received more prednisolone ( 81 % ; st and ard , 63 % ; P = .03 ) and increased advice to obtain primary care review ( 72 % ; st and ard , 33 % ; P < .0001 ) . A total of 180 children were admitted ( 94 ICP , 86 st and ard ) . The rate of recovery was unchanged by ICP . The mean ICP length of stay ( 37.6 hours ; range , 33.5 - 42.4 hours ) , was 93 % of the mean st and ard length of care ( 40.7 hours ; range , 35.9 - 46 ; P = .36 ) . When a discharge checklist was completed ( 60 of 94 cases ) , the mean ICP length of stay was 34.2 hours ( range , 30.5 - 38.4 hours ; P = .07 versus st and ard ) . An ICP result ed in a 30 % reduction in prescribing errors ( mean , 10.4 ; st and ard , 14.8 ; P = .002 ) . Eighty-four of 94 children with an ICP received a 48-hour discharge plan ( 89 % ) versus 35 of 86 children with st and ard care ( 41 % ) . More clinical contacts were observed in children receiving care by an ICP ( mean , 22 , versus st and ard , 19.2 : P = .0004 ) . CONCLUSION An acute asthma/wheeze ICP improved education and prescribing errors , modestly reduced the length of stay when discharge criteria were adhered to , but did not influence recovery time . Further consideration of the effect on staff workload is required The study objective was to determine the impact on quality of care , re source use , and outcomes by developing an emergency department (ED)-based asthma-specific care plan . The design was a time based , prospect i ve cohort and set at an urban university/trauma center , EM residency site , combined adult/pediatric department . Best practice was defined prospect ively for ED asthma patients , leading to an asthma care plan ( ACP ) . Triage nurses were instructed to begin use of ACP when patients presented with asthma as the primary complaint . Charts of all patients diagnosed with asthma during 3-month study period were retrospectively review ed against predefined outcomes . Results were analyzed with chi2 or student 's t tests . After ACP introduction , the timeliness of beta agonist treatments ( three beta agonist treatments within 90 minutes ; 86 % versus 63 % , P < .05 ) and ED length of stay ( LOS ) ( 3.39 + /- 1.88 hrs versus 3.87 + /- 2.12 hrs , P < .05 ) improved . After introduction of ACP , only 55 % of patients diagnosed with asthma had care documented on the ACP ( ACP+ group ) . ACP+ group had more timely beta agonist treatment ( 93 % versus 74 % , P < .01 ) , shorter LOS ( 3.29 + /- 1.90 vs. 3.53 + /- 1.86 hrs , P < 0.5 ) more appropriate steroid dosages ( 67 % versus 41 % , P < .01 ) , and fewer tests ( 41 % versus 59 % , P < .05 ) . No improvements were noted in admission or relapse rates . In conclusion , care plans can improve quality of care and decrease LOS , but may have limited impact on outcomes of admission/discharge or relapse rates AIM The aim of the study was to assess , in a r and omised , controlled design , the efficacy of different strategies to improve childhood asthma management . METHOD Three interventions directed to three groups of general practitioners were compared : Group A - dissemination of a guideline ; Group B - guideline dissemination plus an educational session ; Group C - guideline dissemination , educational session , plus individualised treatment advice based on airway hyperresponsiveness ( AHR ) and symptoms . Efficacy of the three strategies was assessed by evaluating change in AHR in 362 children after one year . RESULTS The overall between-group effect of the severity of AHR was not significantly different ( P=0.09 ) . In Groups A and C an improvement was seen in nocturnal symptoms ( P=0.02 ) and in Group C an improvement was seen in the prescription of inhaled corticosteroids ( P=0.03 ) . CONCLUSION In this study , the combined implementation strategy did not show a clear improvement in the management of children with asthma in general practice BACKGROUND To evaluate the therapeutic and financial benefits of protocol therapy for acute asthma using st and ard medications . MATERIAL S AND METHODS This study employed a sequential design in which the influence of an asthma care path on hospital admissions , length of stay ( LOS ) in the emergency department , and return visits were evaluated for 1 year . This information was contrasted with similar data obtained from the 8 months immediately before the protocol was implemented ( pre protocol ) and a 12-month period after strict adherence to it had declined ( admixture ) . RESULTS In all , 526 acute exacerbations of asthma were treated with the care path , and 429 and 558 episodes were evaluated during the pre protocol and admixture periods , respectively . There were no significant differences between the presenting clinical or physiologic features of any group . With the protocol , 77 % of the patients resolved their symptoms within 1:47 + /- 0.02 hours : minutes of arrival in the emergency department with a 2 % return rate within 24 hours . The algorithms used quickly identified those needing hospitalization . Patients not meeting the criteria for discharge after receiving the treatments employed typically did not resolve their symptoms for days ( average hospital stay 4.1 + /- 0.2 days ) . Compared with the pre protocol period , the care path significantly reduced the LOS by 50 minutes , the number of urgent and intensive care unit admissions by 27 % and 41 % , respectively , and the frequency of return visits within 24 hours by 66 % . Charges to patients and third-party payors decreased $ 395,000 . When adherence to the protocol diminished , LOS , admissions , and returns rose significantly toward pre protocol values and the financial benefits were lost . CONCLUSIONS Asthma protocol therapy , based primarily upon aggressive use of sympathomimetics in association with serial monitoring of key indices of improvement , provides prompt and efficient relief for acute exacerbations of asthma . Such an approach yields significant financial benefit while quickly identifying individuals who require hospitalization , and it also detects physician practice patterns that can have potentially detrimental impacts on patient care |
1,285 | 27,382,000 | The recommendations and practical management tools were review ed as being well organized and helpful , although systemic barriers to implementation were identified .
This up date d guideline supports the previous general recommendation that patients with cancer who have depression may benefit from psychological and /or pharmacologic interventions , without evidence for the superiority of any specific treatment over another . | PURPOSE This report up date s the Cancer Care Ontario Program in Evidence -Based Care guideline for the management of depression in adult patients with cancer .
This guideline covers pharmacologic , psychological , and collaborative care interventions , with a focus on integrating practical management tools to assist clinicians in delivering appropriate treatments for depression in patients with cancer . | BACKGROUND The management of depression in patients with poor prognosis cancers , such as lung cancer , creates specific challenges . We aim ed to assess the efficacy of an integrated treatment programme for major depression in patients with lung cancer compared with usual care . METHODS Symptom Management Research Trials ( SMaRT ) Oncology-3 is a parallel-group , multicentre , r and omised controlled trial . We enrolled patients with lung cancer and major depression from three cancer centres and their associated clinics in Scotl and , UK . Participants were r and omly assigned in a 1:1 ratio to the depression care for people with lung cancer treatment programme or usual care by a data base software algorithm that used stratification ( by trial centre ) and minimisation ( by age , sex , and cancer type ) with allocation concealment . Depression care for people with lung cancer is a manualised , multicomponent collaborative care treatment that is systematic ally delivered by a team of cancer nurses and psychiatrists in collaboration with primary care physicians . Usual care is provided by primary care physicians . The primary outcome was depression severity ( on the Symptom Checklist Depression Scale [ SCL-20 ] , range 0 - 4 ) averaged over the patient 's time in the trial ( up to a maximum of 32 weeks ) . Trial statisticians and data collection staff were masked to treatment allocation , but patients and clinicians could not be masked to the allocations . Analyses were by intention to treat . This trial is registered with Current Controlled Trials , number IS RCT N75905964 . FINDINGS 142 participants were recruited between Jan 5 , 2009 , and Sept 9 , 2011 ; 68 were r and omly allocated to depression care for people with lung cancer and 74 to usual care . 43 ( 30 % ) of 142 patients had died by 32 weeks , all of which were cancer-related deaths . No intervention-related serious adverse events occurred . 131 ( 92 % ) of 142 patients provided outcome data ( 59 in the depression care for people with lung cancer group and 72 in the usual care group ) and were included in the intention-to-treat primary analysis . Average depression severity was significantly lower in patients allocated to depression care for people with lung cancer ( mean score on the SCL-20 1·24 [ SD 0·64 ] ) than in those allocated to usual care ( mean score 1·61 [ SD 0·58 ] ) ; difference -0·38 ( 95 % CI -0·58 to -0·18 ) ; st and ardised mean difference -0·62 ( 95 % CI -0·94 to -0·29 ) . Self-rated depression improvement , anxiety , quality of life , role functioning , perceived quality of care , and proportion of patients achieving a 12-week treatment response were also significantly better in the depression care for people with lung cancer group than in the usual care group . INTERPRETATION Our findings suggest that major depression can be treated effectively in patients with a poor prognosis cancer ; integrated depression care for people with lung cancer was substantially more efficacious than was usual care . Larger trials are now needed to estimate the effectiveness and cost-effectiveness of this care programme in this patient population , and further adaptation of the treatment will be necessary to address the unmet needs of patients with major depression and even shorter life expectancy . FUNDING Cancer Research UK and Chief Scientist Office of the Scottish Government In the context of chronic physical illness , such as breast cancer , depression is associated with increased morbidity , longer periods of hospitalization , and greater overall disability . Prompt diagnosis and effective treatment is , therefore , essential . Several small studies have established the efficacy of tricyclic antidepressants ( TCAs ) in this setting , and the selective serotonin reuptake inhibitors ( SSRIs ) would appear to be an alternative therapeutic option because of their established efficacy and better tolerability profile . This was a multicenter , double-blind , parallel-group study in which 179 women with breast cancer were r and omized to treatment with either the SSRI paroxetine ( 20–40mg/day ) , or the TCA , amitriptyline ( 75–150mg/day ) . After 8-weeks treatment , depressive symptomatology had improved markedly and to a similar extent in both groups on the Montgomery Asberg Depression Rating Scale . Clinical global impression ( CGI ) Global improvement and Patient global evaluation scales indicated that patients were minimally to much improved at study endpoint ; a change from moderately/mildly ill to borderline ill on the CGI severity of Illness scale . A steady improvement in quality of life was also observed in both groups . There were no clinical ly significant differences between the groups . In total , 47 ( 53.4 % ) patients in the paroxetine group and 53 ( 59.6 % ) patients in the amitriptyline group had adverse experiences , the most common of which were the well-recognized side-effects of the antidepressant medications or chemotherapy . Anticholinergic effects were almost twice as frequent in the amitriptyline group ( 19.1 % ) compared with paroxetine ( 11.4 % ) . This study has demonstrated that paroxetine is a suitable alternative to amitriptyline for the treatment of depression in patients with breast cancer Little has been done to study the effectiveness of antidepressants in controlling anxiety/depression in a population of cancer patients . A double‐blind placebo‐controlled study was therefore design ed to assess the effectiveness of 20 mg fluoxetine . Of 115 cancer patients who fulfilled entry criteria for levels of distress , 45 patients were r and omized to a fluoxetine treatment group ( FA ) and 46 patients to a placebo group ( PA ) after a 1‐week placebo period design ed to exclude placebo responders . The Montgomery and Asberg Depression Scale ( MADRS ) , the Hamilton Anxiety Scale ( HAS ) , the Hospital Anxiety and Depression Scale ( HADS ) , the Revised Symptom Checklist ( SCL90‐R ) and the Spitzer Quality of Life Index ( SQOLI ) were used to assess the efficacy of fluoxetine . The response rate , defined by a HADS score lower than 8 after 5 weeks of treatment , was not significantly higher in the FA group ( 11 % ) compared to the PA group ( 7 % ) . Compared to the PA group , patients in the FA group showed a significantly greater decrease in SCL90‐R mean total score after 5 weeks , but not a greater decrease in HADS mean score . No difference between the two groups was found in observer‐reported assessment s ( MADRS , HAS and SQOLI ) . Significantly more drop‐outs were observed in the FA group ( n=15 ) than in the PA group ( n=7 ) , although the frequencies of side‐effects were not significantly different BACKGROUND There is a lack of trials of psychodynamic treatments of depression in breast cancer patients . The purpose of this trial was to determine the efficacy of short-term psychodynamic psychotherapy ( STPP ) in non-metastatic breast cancer patients diagnosed with depression , one of the most frequent mental comorbidities of breast cancer . PATIENTS AND METHODS In a multicenter prospect i ve trial , 157 breast cancer patients with comorbid depression were r and omized to either individual STPP ( intervention group , N=78 ) or ' treatment as usual ' ( control group , TAU , N=79 ) . As our primary outcome measure , we hypothesized a higher rate of remission defined as no diagnosis of depression ( Structured Clinical Interview for DSM-IV ) and reduction in depression score by at least 2 points ( Hospital Anxiety and Depression Scale , HADS-D ) in STPP versus TAU at treatment termination . Secondary outcomes mainly refer to quality of life ( QoL ) . RESULTS In the intention to treat ( ITT ) analysis , 44 % of the STPP group achieved highly significantly more remission than TAU ( 23 % ) . STPP treatment ( OR=7.64 ; P<0.001 ) was the strongest predictor for remission post-treatment ; time was also significant ( OR=0.96 ; P<0.05 ) . A high effect favoring STPP ( d=0.82 ) was observed for the HADS-D score post-treatment ( secondary outcome ) . Regarding further secondary outcomes ( QoL ) , analyses of covariance yielded main effects for group ( favoring STPP with an effect size of at least d=0.5 ) for global QoL , role , emotional and social functioning , pain , treatment side-effects , breast symptoms and upset by hair loss . CONCLUSIONS STPP is an effective treatment of a broad range of depressive conditions in breast cancer patients improving depression and functional QoL. Findings are limited by the drop-out rate ( ∼1/3 ) and delayed post-treatment assessment s. Future trials may consider stepped-care approaches , tailored to patients ' needs and requirements in the acute treatment phase OBJECTIVE Head and neck cancer ( HNC ) patients have a high incidence of cancer-related posttraumatic stress disorder ( PTSD ) and other anxiety and depressive disorders . We report the results from the first pilot r and omized controlled trial in which the efficacy of an early cognitive-behavioral therapy ( CBT ) program was compared with a non-directive supportive counseling ( SC ) intervention in reducing PTSD , general anxiety and depressive symptoms , and improving perceived quality of life in newly diagnosed , distressed HNC patients undergoing radiotherapy . PATIENTS AND METHODS Thirty-five HNC patients ( mean age=54.8 years ; 80 % males ) with elevated levels of PTSD , depression or anxiety were r and omized to seven individual sessions of a multi-modal CBT or non-directive SC , concurrent with patients ' radiotherapy . The SC intervention provided non-directive counseling support . PTSD , anxiety and depressive symptoms ( primary outcomes ) , and cancer-related appraisal s and quality of life ( secondary outcomes ) were assessed pre-intervention ( baseline ) , 1 month , 6 months and 12 months post-intervention by diagnostic clinical interviews and vali date d self-report question naires . RESULTS The CBT and SC interventions were found to be equal in their effects in reducing PTSD and anxiety symptoms both in the short and longer term . However , up to 67 % of patients in the CBT program no longer met clinical or sub- clinical PTSD , anxiety and /or depression by 12 months post-treatment compared with 25 % of patients who received SC . CONCLUSION Findings indicate that the early provision of psychotherapy has utility in reducing PTSD , anxiety and depressive symptoms , and preventing chronic psychopathology in distressed HNC patients Background Depression is common among older cancer patients , but little is known about the optimal approach to caring for this population . This analysis evaluates the effectiveness of the Improving Mood-Promoting Access to Collaborative Treatment ( IMPACT ) program , a stepped care management program for depression in primary care patients who had an ICD-9 cancer diagnosis . Methods Two hundred fifteen cancer patients were identified from the 1,801 participants in the parent study . Subjects were 60 years or older with major depression ( 18 % ) , dysthymic disorder ( 33 % ) , or both ( 49 % ) , recruited from 18 primary care clinics belonging to 8 health-care organizations in 5 states . Patients were r and omly assigned to the IMPACT intervention ( n = 112 ) or usual care ( n = 103 ) . Intervention patients had access for up to 12 months to a depression care manager who was supervised by a psychiatrist and a primary care provider and who offered education , care management , support of antidepressant management , and brief , structured psychosocial interventions including behavioral activation and problem-solving treatment . Results At 6 and 12 months , 55 % and 39 % of intervention patients had a 50 % or greater reduction in depressive symptoms ( SCL-20 ) from baseline compared to 34 % and 20 % of usual care participants ( P = 0.003 and P = 0.029 ) . Intervention patients also experienced greater remission rates ( P = 0.031 ) , more depression-free days ( P < 0.001 ) , less functional impairment ( P = 0.011 ) , and greater quality of life ( P = 0.039 ) at 12 months than usual care participants . Conclusions The IMPACT collaborative care program appears to be feasible and effective for depression among older cancer patients in diverse primary care setting 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 Major depressive disorder severely impairs the quality of life of patients with medical disorders such as cancer , but evidence to guide its management is scarce . We aim ed to assess the efficacy and cost of a nurse-delivered complex intervention that was design ed to treat major depressive disorder in patients who have cancer . METHODS We did a r and omised trial in a regional cancer centre in Scotl and , UK . 200 out patients who had cancer with a prognosis of greater than 6 months and major depressive disorder ( identified by screening ) were eligible and agreed to take part . Their mean age was 56.6 ( SD 11.9 ) years , and 141 ( 71 % ) were women . We r and omly assigned 99 of these participants to usual care , and 101 to usual care plus the intervention , with minimisation for sex , age , diagnosis , and extent of disease . The intervention was delivered by a cancer nurse at the centre over an average of seven sessions . The primary outcome was the difference in mean score on the self-reported Symptom Checklist-20 depression scale ( range 0 to 4 ) at 3 months after r and omisation . Analysis was by intention to treat . This trial is registered as IS RCT N84767225 . FINDINGS Primary outcome data were missing for four patients . For 196 patients for whom we had data at 3 months , the adjusted difference in mean Symptom Checklist-20 depression score , between those who received the intervention and those who did not , was 0.34 ( 95 % CI 0.13 - 0.55 ) . This treatment effect was sustained at 6 and 12 months . The intervention also improved anxiety and fatigue but not pain or physical functioning . It cost an additional pound sterling 5278 ( US$ 10 556 ) per quality -adjusted life-year gained . INTERPRETATION The intervention-Depression Care for People with Cancer-offers a model for the management of major depressive disorder in patients with cancer and other medical disorders who are attending specialist medical services that is feasible , acceptable , and potentially cost effective One hundred and fifty‐two women undergoing mastectomy were r and omly assigned to routine care or routine care plus monitoring by a specialist nurse . The nurse detected and referred 76 % of her patients for psychiatric help . Only 15 % of the routine care subjects that warranted help were referred . Twelve to eighteen months after surgery , morbid anxiety and depression were less common in the monitored ( 5 % and 5 % ) than in the control ( 30 % and 50 % ) group . This difference appeared to be due primarily to psychiatric treatment which included antidepressant medication , anxiolytic drugs , and supportive psychotherapy . Few affective disorders remitted without such treatment . In a further study , the effects of antidepressant medication plus cognitive therapy and cognitive therapy alone were compared . Both treatments alleviated depression in the short term but the improvement was sustained in the long term only in those given combined treatment CONTEXT Pain and depression are 2 of the most prevalent and treatable cancer-related symptoms , yet they frequently go unrecognized , undertreated , or both . OBJECTIVE To determine whether central ized telephone-based care management coupled with automated symptom monitoring can improve depression and pain in patients with cancer . DESIGN , SETTING , AND PATIENTS R and omized controlled trial conducted in 16 community-based urban and rural oncology practice s involved in the Indiana Cancer Pain and Depression ( INCPAD ) trial . Recruitment occurred from March 2006 through August 2008 and follow-up concluded in August 2009 . The participating patients had depression ( Patient Health Question naire-9 score > or = 10 ) , cancer-related pain ( Brief Pain Inventory [ BPI ] worst pain score > or = 6 ) , or both . INTERVENTION The 202 patients r and omly assigned to receive the intervention and 203 to receive usual care were stratified by symptom type . Patients in the intervention group received central ized telecare management by a nurse-physician specialist team coupled with automated home-based symptom monitoring by interactive voice recording or Internet . MAIN OUTCOME MEASURES Blinded assessment at baseline and at months 1 , 3 , 6 , and 12 for depression ( 20-item Hopkins Symptom Checklist [ HSCL-20 ] ) and pain ( BPI ) severity . RESULTS Of the 405 participants enrolled in the study , 131 had depression only , 96 had pain only , and 178 had both depression and pain . Of the 274 patients with pain , 137 patients in the intervention group had greater improvements in BPI pain severity over the 12 months of the trial whether measured as a continuous severity score or as a categorical pain responder ( > or = 30 % decrease in BPI ) than the 137 patients in the usual-care group ( P < .001 for both ) . Similarly , of the 309 patients with depression , the 154 patients in the intervention group had greater improvements in HSCL-20 depression severity over the 12 months of the trial whether measured as a continuous severity score or as a categorical depression responder ( > or = 50 % decrease in HSCL ) than the 155 patients in the usual care group ( P < .001 for both ) . The st and ardized effect size for between-group differences at 3 and 12 months was 0.67 ( 95 % confidence interval [ CI ] , 0.33 - 1.02 ) and 0.39 ( 95 % CI , 0.01 - 0.77 ) for pain , and 0.42 ( 95 % CI , 0.16 - 0.69 ) and 0.41 ( 95 % CI , 0.08 - 0.72 ) for depression . CONCLUSION Central ized telecare management coupled with automated symptom monitoring result ed in improved pain and depression outcomes in cancer patients receiving care in geographically dispersed urban and rural oncology practice s. TRIAL REGISTRATION clinical trials.gov Identifier : NCT00313573 BACKGROUND Medical conditions are often complicated by major depression , with consequent additional impairment of quality of life . We aim ed to compare the effectiveness of an integrated treatment programme for major depression in patients with cancer ( depression care for people with cancer ) with usual care . METHODS SMaRT Oncology-2 is a parallel-group , multicentre , r and omised controlled effectiveness trial . We enrolled out patients with major depression from three cancer centres and their associated clinics in Scotl and , UK . Participants were r and omly assigned in a 1:1 ratio to the depression care for people with cancer intervention or usual care , with stratification ( by trial centre ) and minimisation ( by age , primary cancer , and sex ) with allocation concealment . Depression care for people with cancer is a manualised , multicomponent collaborative care treatment that is delivered systematic ally by a team of cancer nurses and psychiatrists in collaboration with primary care physicians . Usual care is provided by primary care physicians . Outcome data were collected up until 48 weeks . The primary outcome was treatment response ( ≥50 % reduction in Symptom Checklist Depression Scale [ SCL-20 ] score , range 0 - 4 ) at 24 weeks . Trial statisticians and data collection staff were masked to treatment allocation , but participants could not be masked to the allocations . Analyses were by intention to treat . This trial is registered with Current Controlled Trials , number IS RCT N40568538 . FINDINGS 500 participants were enrolled between May 12 , 2008 , and May 13 , 2011 ; 253 were r and omly allocated to depression care for people with cancer and 247 to usual care . 143 ( 62 % ) of 231 participants in the depression care for people with cancer group and 40 ( 17 % ) of 231 in the usual care group responded to treatment : absolute difference 45 % ( 95 % CI 37 - 53 ) , adjusted odds ratio 8·5 ( 95 % CI 5·5 - 13·4 ) , p<0·0001 . Compared with patients in the usual care group , participants allocated to the depression care for people with cancer programme also had less depression , anxiety , pain , and fatigue ; and better functioning , health , quality of life , and perceived quality of depression care at all timepoints ( all p<0·05 ) . During the study , 34 cancer-related deaths occurred ( 19 in the depression care for people with cancer group , 15 in the usual care group ) , one patient in the depression care for people with cancer group was admitted to a psychiatric ward , and one patient in this group attempted suicide . None of these events were judged to be related to the trial treatments or procedures . INTERPRETATION Our findings suggest that depression care for people with cancer is an effective treatment for major depression in patients with cancer . It offers a model for the treatment of depression comorbid with other medical conditions . FUNDING Cancer Research UK and Chief Scientist Office of the Scottish Government Depression is a major complication of cancer . The efficacy and safety of mianserin were evaluated in a r and omized placebo‐controlled trial of 73 depressed women with cancer . According to RDC diagnosis , all patients showed situational major depression . Both groups were well matched for cancer localization , clinical stages , Karnofsky scores , duration of depression , baseline values on the Hamilton Depression Rating Scale ( HDRS ) , Zung Self‐Rating Depression Scale ( ZSRDS ) , and Clinical Global Impression of Illness Severity ( CGI‐S ) , and for type of depression , whether dominantly depressive or depressive‐anxious . Between days 7–21 , there were significantly fewer dropouts with mianserin ( 7 ) than with placebo ( 15 ) . When compared with placebo , there were significant improvements for mianserin for HDRS on days 7 , 21 and 28 , for ZSRDS on days 7 and 28 , and for CGI‐S on days 7 , 14 , 21 and 28 . According to Clinical Global Impression of Illness Improvement ( CGI‐I ) there were significantly more responders with mianserin ( 28 ) than with placebo ( 18 ) . The efficacy index for mianserin was significantly greater than for placebo on days 21 and 28 . At the end of the trial the scores for HDRS sleep disturbance factor and HDRS anxiety‐somatization factor were significantly reduced for mianserin than for placebo . There were no significant differences in side‐effects between treatment groups . It is concluded that mianserin is superior to placebo in reducing the severity and duration of depression which is present especially in patients with advanced cancer . The fact that side‐effects were not a problem with mianserin and that mianserin treatment was safe when used in association with other anticancer drugs suggests that mianserin can be prescribed routinely for alleviating depression in cancer patients In a pilot study , 55 low-income Latina patients with breast or cervical cancer and comorbid depression were r and omly assigned to receive collaborative care as part of the Multifaceted Oncology Depression Program or usual care . Relative to patients in the usual care condition , patients receiving collaborative care were more likely to show > or=50 % improvement in depressive symptoms as measured by the Personal Health Question naire ( OR=4.51 , 95 % CI=1.07 - 18.93 ) . Patients in the collaborative care program were also more likely to show improvement in emotional well-being ( increase of 2.15 ) as measured by the Functional Assessment of Cancer Therapy Scale than were those receiving usual care ( decrease of 0.50 ) ( group difference=2.65 , 95 % CI : 0.18 - 5.12 ) . Despite health system , provider , and patient barriers to care , these initial results suggest that patients in public sector oncology clinics can benefit from onsite depression treatment Abstract Background : This study aims to evaluate the effects of Group Cognitive Behavioral Therapy ( GCBT ) in treating major depression in Chinese women with breast cancer . Methods : Sixty-two breast cancer patients diagnosed with major depression were r and omly assigned to GCBT group ( N = 31 ) or a waiting list control group provided with an educational booklet ( N = 31 ) . The primary outcome measure was the 17-Item Hamilton Depression Rating Scale ( 17-HAMD ) . The second outcome measures were Self-Rating Anxiety Scale , Functional Assessment of Cancer Therapy – Breast and Self-Esteem Scale ( SES ) . Assessment s were carried out at completion of the study and six-month afterwards . Results : Patients in the GCBT group had a significant reduction in the 17-HAMD mean score by 9 points ( p < 0.001 ) , more than any reduction among patients in the control group from baseline to the end of therapy and a significant 7 points ( p < 0.001 ) more reduction from baseline to six-month follow-up . GCBT also yielded significantly greater improvement than the control group with regard to quality of life ( QoL ; p < 0.01 ) and self-esteem ( p < 0.05 ) . No significant differences were found between groups on improving anxiety ( p > 0.05 ) . Conclusion : The results of this trial suggest that GCBT is effective for treating major depression , as well as for improving QoL and self-esteem in breast cancer patients . Trial Registration : Chictr.org OBJECTIVE Major depression is the most common psychiatric disorder among breast cancer patients and is associated with substantial impairment . Although some research has explored the utility of psychotherapy with breast cancer patients , only 2 small trials have investigated the potential benefits of behavior therapy among patients with well-diagnosed depression . METHOD In a primarily Caucasian , well-educated sample of women ( age = 55.4 years , SD = 11.9 ) diagnosed with breast cancer and major depression ( n = 80 ) , this study was a r and omized clinical trial testing the efficacy of 8 sessions of behavioral activation treatment for depression ( BATD ) compared to problem-solving therapy . Primary outcome measures assessed depression , environmental reward , anxiety , quality of life , social support , and medical outcomes . RESULTS Across both treatments , results revealed strong treatment integrity , excellent patient satisfaction with treatment protocol s , and low patient attrition ( 19 % ) . Intent-to-treat analyses suggested both treatments were efficacious , with both evidencing significant pre-post treatment gains across all outcome measures . Across both treatments , gains were associated with strong effect sizes , and based on response and remission criteria , a reliable change index , and numbers-needed-to-treat analyses , approximately ¾ of patients exhibited clinical ly significant improvement . No significant group differences were found at posttreatment . Treatment gains were maintained at 12-month follow-up , with some support for stronger maintenance of gains in the BATD group . CONCLUSIONS BATD and problem-solving interventions represent practical interventions that may improve psychological outcomes and quality of life among depressed breast cancer patients . Study limitations and future research directions are discussed This is a 4 week , r and omized , double-blind , placebo-controlled study to examine the effects of methylpheni date as add-on therapy to mirtazapine compared to placebo for treatment of depression in terminally ill cancer patients . It involved 88 terminally ill cancer patients from University of Malaya Medical Centre , Kuala Lumpur , Malaysia . They were r and omized and treated with either methylpheni date or placebo as add on to mirtazapine . The change in Montgomery-Åsberg Depression Rating Scale ( MADRS ) score from baseline to day 3 was analyzed by linear regression . Changes of MADRS and Clinical Global Impression-Severity Scale ( CGI-S ) over 28 days were analyzed using mixed model repeated measures ( MMRM ) . Secondary analysis of MADRS response rates , defined as 50 % or more reduction from baseline score . A significantly larger reduction of Montgomery-Åsberg Depression Rating Scale ( MADRS ) score in the methylpheni date group was observed from day 3 ( B=4.14 ; 95 % CI=1.83 - 6.45 ) . Response rate ( defined as 50 % or more reduction from baseline MADRS score ) in the methylpheni date treated group was superior from day 14 . Improvement in Clinical Global Impression-Severity Scale ( CGI-S ) was greater in the methylpheni date treated group from day 3 until day 28 . The drop-out rates were 52.3 % in the methylpheni date group and 59.1 % in the placebo group ( relative risk=0.86 , 95%CI=0.54 - 1.37 ) due to cancer progression . Nervous system adverse events were more common in methylpheni date treated subjects ( 20.5 % vs 9.1 % , p=0.13 ) . In conclusions , methylpheni date as add on therapy to mirtazapine demonstrated an earlier antidepressant response in terminally ill cancer patients , although at an increased risk of the nervous system side effects PURPOSE To determine the effectiveness of the Alleviating Depression Among Patients With Cancer ( ADAPt-C ) collaborative care management for major depression or dysthymia . PATIENTS AND METHODS Study patients included 472 low-income , predominantly female Hispanic patients with cancer age > or= 18 years with major depression ( 49 % ) , dysthymia ( 5 % ) , or both ( 46 % ) . Patients were r and omly assigned to intervention ( n = 242 ) or enhanced usual care ( EUC ; n = 230 ) . Intervention patients had access for up to 12 months to a depression clinical specialist ( supervised by a psychiatrist ) who offered education , structured psychotherapy , and maintenance/relapse prevention support . The psychiatrist prescribed antidepressant medications for patients preferring or assessed to require medication . RESULTS At 12 months , 63 % of intervention patients had a 50 % or greater reduction in depressive symptoms from baseline as assessed by the Patient Health Question naire-9 ( PHQ-9 ) depression scale compared with 50 % of EUC patients ( odds ratio [ OR ] = 1.98 ; 95 % CI , 1.16 to 3.38 ; P = .01 ) . Improvement was also found for 5-point decrease in PHQ-9 score among 72.2 % of intervention patients compared with 59.7 % of EUC patients ( OR = 1.99 ; 95 % CI , 1.14 to 3.50 ; P = .02 ) . Intervention patients also experienced greater rates of depression treatment ( 72.3 % v 10.4 % of EUC patients ; P < .0001 ) and significantly better quality -of-life outcomes , including social/family ( adjusted mean difference between groups , 2.7 ; 95 % CI , 1.22 to 4.17 ; P < .001 ) , emotional ( adjusted mean difference , 1.29 ; 95 % CI , 0.26 to 2.22 ; P = .01 ) , functional ( adjusted mean difference , 1.34 ; 95 % CI , 0.08 to 2.59 ; P = .04 ) , and physical well-being ( adjusted mean difference , 2.79 ; 95 % CI , 0.49 to 5.1 ; P = .02 ) . CONCLUSION ADAPt-C collaborative care is feasible and results in significant reduction in depressive symptoms , improvement in quality of life , and lower pain levels compared with EUC for patients with depressive disorders in a low-income , predominantly Hispanic population in public sector oncology clinics PURPOSE To determine whether fluoxetine improves overall quality of life ( QOL ) in advanced cancer patients with symptoms of depression revealed by a simple survey . PATIENTS AND METHODS One hundred sixty-three patients with an advanced solid tumor and expected survival between 3 and 24 months were r and omly assigned in a double-blinded fashion to receive either fluoxetine ( 20 mg daily ) or placebo for 12 weeks . Patients were screened for at least minimal depressive symptoms and assessed every 3 to 6 weeks for QOL and depression . Patients with recent exposure to antidepressants were excluded . RESULTS The groups were comparable at baseline in terms of age , sex , disease distribution , performance status , and level of depressive symptoms . One hundred twenty-nine patients ( 79 % ) completed at least one follow-up assessment . Analysis using generalized estimating equation modeling revealed that patients treated with fluoxetine exhibited a significant improvement in QOL as shown by the Functional Assessment of Cancer Therapy-General , compared with patients given placebo ( P = .01 ) . Specifically , the level of depressive symptoms expressed was lower in patients treated with fluoxetine ( P = .0005 ) , and the subgroup of patients showing higher levels of depressive symptoms on the two- question screening survey were the most likely to benefit from treatment . CONCLUSION In this mix of patients with advanced cancer who had symptoms of depression as determined by a two- question bedside survey , use of fluoxetine was well tolerated , overall QOL was improved , and depressive symptoms were reduced OBJECTIVE To compare narrative therapy ( NT ) plus escitalopram versus escitalopram plus usual care on quality of life and depressive symptomatology of depressed patients with oncologic disease . METHODS A total of 72 subjects ( mean age 54.6 years ) , predominantly female with non-metastatic breast , lung and colon cancer and depressive disorder ( DSM-IV-TR ) were r and omized to receive treatment with NT plus escitalopram ( n=39 ) or escitalopram ( 10 - 20 mg QD ) plus usual care ( n=33 ) . Main endpoints were improvement in dimensions of quality of life measured by the European Organization for Research and Treatment of Cancer Quality of Life Question naire C-30 and reduction of depressive symptoms using the Hospital Anxiety and Depression Scale at weeks 12 and 24 . RESULTS The combined therapy group showed significantly greater improvement in all the functioning dimensions ( p<0.01 ) , pain scale ( p=0.02 ) , global health ( p=0.02 ) , and global quality of life ( p=0.007 ) at weeks 12 and 24 . There were no statistically significant differences in depressive symptomatology between the groups . From week 12 to week 24 study retention was higher in the combined treatment group ( p=0.01 ) . CONCLUSIONS Brief NT in combination with escitalopram was superior to usual care and escitalopram in improving functioning dimensions of quality life To examine the prevalence of depressive symptoms and its relationship with quality -of-life domains in home-care cancer patients at an advanced stage of illness , 86 patients were given psychological tests for depression ( Hospital Anxiety Depression Scale ) ( HAD ) and quality of life ( EORTC-QLQ-C30 ) 1 week after admission to the home-care program . Using a proper cut-off score on the HAD-Depression subscale , depressive symptoms were reported by 45 % of the patients . The quality of life of depressed patients was more affected than non-depressed patients in the social , emotional , cognitive , and physical domains . Significant correlations were found between depression scores and impairment in most quality -of-life areas . These findings support the importance of depression and quality -of-life evaluation in patients with advanced cancer who are followed in a home-care setting . This evaluation is needed to provide patients , their families , and caregivers with appropriate psychosocial interventions BACKGROUND Psychotropic drugs are commonly prescribed for various psychological complaints in cancer patients . We aim to examine the prescription pattern in cancer patients of three common psychotropic drugs : benzodiazepine , antidepressant and antipsychotic . METHODS This is a retrospective case-control study . Data were extracted from the Agis Health Data base . This insurance data base contains the healthcare consumption of 1.3 million inhabitants of the Netherl and s. We analyzed the use of psychotropics in cancer patients and an equally sized r and omly selected control group of noncancer patients from 2006 to 2008 . Odds ratio ( OR ) were adjusted for age , gender , immigrant status , neighborhood socio-economic status , and premorbid medical condition . Additionally , the numbers of new user in the 3 months after cancer was diagnosed and in the 3 months before death were compared . RESULTS A total of 113 887 cancer patients and 121 395 control subjects were included . Cancer patients were significantly more often prescribed psychotropic drugs ( adjusted OR : benzodiazepines = 1.70 , CI = 1.67 - 1.74 ; antidepressants = 1.38 , CI = 1.34 - 1.42 ; and antipsychotics = 1.70 , CI = 1.62 - 1.77 ) . Lower socio-economic status , immigrant , and premorbid chronic medical conditions were significantly associated with higher risk of psychotropic use . Odds for a new prescription for all three psychotropic drugs were significantly less in the first 3 months after cancer diagnosis than the 3 months before death ( benzodiazepine , OR = 0.673 , CI = 0.647 - 0.705 ; antidepressant , OR = 0.592 , CI = 0.544 - 0.644 ; antipsychotic , OR = 0.177 , CI = 0.165 - 0.190 ) CONCLUSIONS : Psychotropic drug prescription is common in cancer patients , starts soon after diagnosis , and increases in the terminal stage . Prescription rates were significantly higher in patients from lower socio-economic group , immigrants , or with premorbid chronic medical condition The efficacy of problem-solving therapy ( PST ) to reduce psychological distress was assessed among a sample of 132 adult cancer patients . A second condition provided PST for both the patient and a significant other . At posttreatment , all participants receiving PST fared significantly better than waiting list control patients . Further , improvements in problem solving were found to correlate significantly with improvements in psychological distress and overall quality of life . No differences in symptom reduction were identified between the 2 treatment protocol s. At a 6-month follow-up , however , patients who received PST along with their significant other reported lower levels of psychological distress as compared with members of the PST-alone condition on approximately half of the outcome measures . These effects were further maintained 1-year posttreatment OBJECTIVE This study assessed longer-term outcomes of low-income patients with cancer ( predominantly female and Hispanic ) after treatment in a collaborative model of depression care or in enhanced usual care . METHODS The r and omized controlled trial , conducted in safety-net oncology clinics , recruited 472 patients with major depression symptoms . Patients r and omly assigned to a 12-month intervention ( a depression care manager and psychiatrist provided problem-solving therapy , antidepressants , and symptom monitoring and relapse prevention ) or enhanced usual care ( control group ) were interviewed at 18 and 24 months after enrollment . RESULTS At 24 months , 46 % of patients in the intervention group and 32 % in the control group had a ≥50 % decrease in depression score over baseline ( odds ratio=2.09 , 95 % confidence interval=1.13 - 3.86 ; p=.02 ) ; intervention patients had significantly better social ( p=.03 ) and functional ( p=.01 ) well-being . Treatment receipt among intervention patients declined ( 72 % , 21 % , and 18 % at 12 , 18 , and 24 months , respectively ) ; few control group patients reported treatment receipt ( 10 % , 6 % , and 13 % , respectively ) . Significant differences in receipt of counseling or antidepressants disappeared at 24 months . Depression recurrence was similar between groups ( intervention , 36 % ; control , 39 % ) . Among patients with depression recurrence , intervention patients were more likely to receive treatment after 12 months ( 34 % versus 10 % ; p=.03 ) . At 24 months , attrition ( 262 patients , 56 % ) did not vary by group ; 22 % were deceased , 20 % declined further participation , and 14 % could not be located . CONCLUSIONS Collaborative care reduced depression symptoms and enhanced quality of life ; however , results call for ongoing depression symptom monitoring and treatment for low-income cancer survivors BACKGROUND This study was conducted to determine the efficacy and tolerability of fluoxetine and desipramine in treating depressive symptoms in women with cancer . METHOD In this prospect i ve , 6-week , double-blind , placebo-controlled trial , we compared fluoxetine with desipramine in treating depressive symptoms in 40 women diagnosed with cancer . Scales used to measure efficacy and tolerability were the Hamilton Depression Rating Scale ( HAM-D ) , the Hamilton Anxiety Rating Scale ( HAM-A ) , the Clinical and Patient 's Global Impression ( CGI and PGI ) scales , the Functional Living Index for Cancer ( FLIC ) , the Memorial Pain Assessment Card ( MPAC ) , and the SF-36 Health Survey . RESULTS Fluoxetine and desipramine treatments improved depression and anxiety symptoms . There was a trend towards significance in improvement of FLIC scores ( as evidence d by greater numerical improvements with fluoxetine treatment ) . Fluoxetine treatment alone was associated with statistically significant improvements in MPAC Mood scale scores . Both treatments showed statistically significant improvements in the quality of life SF-36 scores in Role Emotional , Social Functioning , Mental Health , and Vitality . CONCLUSIONS Both fluoxetine and desipramine were effective and well-tolerated in improving depressive symptoms and quality of life in women with advanced cancer . Fluoxetine may offer greater benefit to these patients , as evidence d by greater improvements in fluoxetine-treated patients on several quality of life measures . Our results , while meaningful , should be confirmed in a larger patients sample . However , experience from studies of antidepressant use in patients with advanced cancer has shown that intercurrent disease and treatment variables make it difficult to conduct large studies PURPOSE Distress has been recognized as the sixth vital sign in cancer care and several guidelines recommend routine screening . Despite this , screening for distress is rarely conducted and infrequently evaluated . METHODS A program of routine online screening for distress was implemented for new patients with breast and lung cancer . Patients were r and omly assigned to one of three conditions : ( 1 ) minimal screening : the distress thermometer ( DT ) only plus usual care ; ( 2 ) full screening : DT , problem checklist , Psychological Screen for Cancer part C measuring anxiety and depression , a personalized report summarizing concerns and the report on the medical file ; or ( 3 ) triage : full screening plus optional personalized phone triage with referral to re sources . Patients in all conditions received an information packet and were reassessed 3 months later with the full screening battery . RESULTS Five hundred eighty-five patients with breast cancer and 549 patients with lung cancer were assessed at baseline ( 89 % of all patients ) , and 75.5 % retained for follow-up . High prevalence of baseline distress was found across patients . Twenty percent fewer patients with lung cancer in triage continued to have high distress at follow-up compared to those in the other two groups , and patients with breast cancer in the full screening and triage conditions showed lower distress at follow-up than those in minimal screening . The best predictor of decreased anxiety and depression in full screening and triage conditions was receiving a referral to psychosocial services . CONCLUSION Routine online screening is feasible in a large cancer center and may help to reduce future distress levels , particularly when coupled with uptake of appropriate re sources Background Major depression and other depressive conditions are common in people with cancer . However , because of the overlap between medical and psychiatric symptoms , these conditions are not easily detectable in clinical practice . Moreover , it is particularly challenging to distinguish between pathological and normal reactions to such a severe illness . It has been widely recognized that depressive symptoms , even in subthreshold manifestations , have a negative impact in terms of quality of life , compliance with anticancer treatment , suicide risk , and likely even the mortality rate for the cancer itself . Thus , providing better interventions to people with cancer and depressive symptoms is an important goal . There is still uncertainty on the true efficacy of antidepressants for the treatment of depression in people with cancer , as data from r and omized controlled trials ( RCTs ) in such a population are few and often contrasting . For these reasons , a systematic review was warranted Although many studies have documented patterns of emotional distress in persons undergoing radiation treatment for cancer , there have been few controlled evaluations of counseling or psychotherapy outcomes with these persons . In this research , the effects of cognitive-behavioral and socially supportive group therapy were evaluated . A total of 72 depressed cancer patients were r and omly assigned to one of three conditions -- cognitive-behavioral treatment , social support , or a no-treatment control condition . Before and after intervention and at 6-month followup , study participants were individually assessed by using measures of symptom distress . Relative to the comparison group , both the cognitive-behavioral and social support therapies result ed in less depression , hostility , and somatization . The social support intervention also result ed in fewer psychiatric symptoms and reduced maladaptive interpersonal sensitivity and anxiety . It was concluded that both group therapies can reduce symptoms of distress for depressed persons undergoing radiation treatment for cancer . Both forms of therapy result ed in improvements in psychosocial function ( compared with no treatment at all ) , but social support groups demonstrated more changes that were evident at 6-month followup . Further research is needed to evaluate the differential effectiveness of mental health services provided to cancer patients undergoing radiation OBJECTIVE This study compared the efficacy and safety of paroxetine and desipramine with those of placebo in the treatment of depressive disorders in adult women with breast cancer , stages I-IV . METHOD In a double-blind , placebo-controlled study , 35 female out patients with breast cancer and DSM-III-R major depression or adjustment disorder with depressed mood were r and omly assigned to treatment with paroxetine ( N=13 ) , desipramine ( N=11 ) , or placebo ( N=11 ) for 6 weeks . Primary efficacy was assessed by change from baseline in score on the 21-item Hamilton Rating Scale for Depression ( HAM-D ) , and the secondary outcome measure was change from baseline in the Clinical Global Impressions-Severity of Illness scale ( CGI-S ) score . RESULTS Mean changes in the total HAM-D and CGI-S scores from baseline to 6-week endpoint for the paroxetine and desipramine groups were not significantly different than those for the placebo-treated group . An unusually high rate of response ( defined as > or=50 % improvement in the HAM-D score ) in the placebo group was observed ( 55 % [ N=6 ] ) ; adverse events precipitated patient discontinuation in the active treatment groups ( 9 % [ N=1 ] for desipramine , 15 % [ N=2 ] for paroxetine ) similar to that in the placebo-treated patients ( 18 % [ N=2 ] ) . Improvement on symptom dimensions within the HAM-D and Hamilton Rating Scale for Anxiety ( depressive , anxiety , cognitive , neurovegetative , or somatic ) was also similar between groups . CONCLUSION The small number of women in this study most likely contributed to the lack of observed differences in efficacy observed during the 6 weeks of treatment . R and omized , placebo-controlled trials of adequate power seeking to determine efficacy of antidepressants in the United States for the treatment of women with breast cancer and comorbid depression remain of paramount importance BACKGROUND Anxiety and depression are the two most frequent comorbidities of tumour patients . At present , it is unclear to which degree a patient 's psychological condition can be altered during the treatment period and if psycho-oncological support positively affects a patient 's psychological condition . METHODS In a r and om sample analyses , 131 patients beginning inpatient treatment at a hospital specialising in surgical oncology were either classified as ' low-risk ' or ' high-risk ' , according to the HADS . Patients from both categories were then r and omly placed in either a low-threshold ' intervention ' group or an ' observation ' group . Anxiety and depression levels were measured again with the HADS scale prior to the patients discharge from the department of surgical oncology , and at a follow up 12 months after . RESULTS Our findings showed a significant reduction of anxiety and depression in the high-risk patients who had undergone psycho-oncological intervention at the end of inpatient care and even a year after discharge from the hospital . The effects of psychological intervention could be observed in terms of anxiety and depression in the group of high-risk patients during the hospital stay . In the other three groups , no statistically significant changes could be measured . CONCLUSION Cancer patients on a surgical ward benefit from psycho-oncological support especially at an early stage of therapy but also over a long time after discharge from the hospital . The aim of all interventions should be to decrease psychological distress and disorders and thereby improve the quality of life for cancer patients |
1,286 | 24,964,976 | Differences between treatments were negligible in terms of clinical outcomes , so the treatment with the lowest cost appears to be most cost-effective .
Total FS costs were estimated to be lowest , and FS was marginally more effective than surgery .
However , relative effectiveness was sensitive to the model time horizon .
Threshold analysis indicated that EVLA and RFA might be considered cost-effective if their costs were similar to those for surgery .
This assessment of currently available evidence suggests there is little to choose between surgery and the minimally invasive techniques in terms of efficacy or safety , so the relative cost of the treatments becomes one of the deciding factors . | BACKGROUND A Health Technology Assessment was conducted to evaluate the relative clinical effectiveness and cost-effectiveness of minimally invasive techniques ( foam sclerotherapy ( FS ) , endovenous laser ablation ( EVLA ) and radiofrequency ablation ( RFA ) ) for managing varicose veins , in comparison with traditional surgery . | OBJECTIVES Comparison of Reverse Foam Sclerotherapy of the great saphenous vein ( GSV ) combed with sapheno-femoral junction ( SFJ ) ligation to st and ard ( Babcock ) stripping and invagination ( Pin ) stripping in a prospect i ve clinical series . DESIGN Prospect i ve clinical series . MATERIAL S AND METHODS 90 consecutive limbs of 82 patients with incompetence of the GSV result ing in varicose veins were prospect ively r and omised into 3 groups of 30 , treated by SFJ ligation and either reverse foam sclerotherapy , st and ard stripping or invagination stripping of the GSV . Outcomes were assessed post-operatively and at 2-weeks follow-up . Peri-operative blood loss ( 24 hrs ) , analgesic requirement , bruising and residual varicosities were assessed . Bruising was assessed by both patients and independent assessors using question naires . RESULTS SFJ ligation plus reverse foam sclerotherapy of the GSV was associated with significantly less blood loss , bruising and post-op discomfort than either of the stripping techniques . ( p<0.001 , Mann-Whitney ) CONCLUSION St and ard stripping of the GSV and invagination stripping are not associated with major discomfort and problems in the early post-operative period . SFJ ligation and GSV reverse foam sclerotherapy yielded greater patient satisfaction with less post-op bruising and discomfort and reduced analgesic requirements Endovenous laser ablation ( EVLA ) and radiofrequency ablation ( RFA ) are both associated with excellent technical , clinical and patient‐reported outcomes for the treatment of varicose veins . The aim of this study was to compare the techniques in a r and omized clinical trial OBJECTIVES To assess the quality of life of patients undergoing sapheno-femoral junction ( SFJ ) ligation and long saphenous vein stripping ( LSV ) , using two different techniques . DESIGN Prospect i ve , r and omised trial . MATERIAL S AND METHODS Eighty patients were recruited and r and omised to either Perforate Invagination ( PIN ) stripping ( 43 ) or Conventional stripping ( 37 ) . Patients completed the Short Form 36 ( SF-36 ) and EuroQol ( EQ ) question naires preoperatively , and postoperatively at 6 weeks and 6 months . RESULTS Bodily pain , role function and physical summary were significantly improved at 6 months in the PIN stripping group . In the Conventional group , bodily pain and physical function were similarly improved , but not role function . EQ global quality of life was significantly and progressively improved at 6 weeks and 6 months in the PIN group ( global score p<0.003 ; self-rated score p < 0.001 ) . In the Conventional group there was no overall improvement in global score or self-rated health . CONCLUSIONS Primary varicose vein surgery is associated with significant and progressive improvements in quality of life scores . Whilst overall quality of health does improve in the Conventional group , this appears to be to a lesser extent than in the PIN group BACKGROUND Although endovenous laser ablation for varicose veins is replacing surgical stripping , proper economic evaluation with adequate follow-up in a r and omised clinical trial is important for considered policy decisions regarding the implementation of new techniques . METHODS Data from a r and omised controlled trial comparing cryostripping and endovenous laser ablation in 120 patients were combined to study Short Form ( SF ) 6D outcome , costs and cost-effectiveness 2 years after treatment . Incremental cost per quality -adjusted life year ( QALY ) gained 2 years after treatment was calculated using different strategies , and uncertainty was assessed with bootstrapping . RESULTS Over the total study period , mean SF-6D scores improved slightly from 0.78 at baseline to 0.80 at 2 years for patients who underwent cryostripping and from 0.77 to 0.79 for patients who underwent endovenous laser . QALY ( SF-6D ) was 1.59 in patients who underwent cryostripping and 1.60 in patients who underwent endovenous laser 2 years after treatment . The costs of cryostripping and endovenous laser per patient were euro 2651 and euro 2783 , respectively . Bootstrapping indicated that cryostripping was associated with an incremental cost-effectiveness ratio of euro 32 per QALY gained . With regard to different strategies , outpatient cryostripping was less costly and more effective 2 years after treatment . CONCLUSION In this study , in terms of costs per QALY gained , outpatient cryostripping appeared to be the dominant strategy , but endovenous laser yielded comparable outcomes for a relatively little additional cost OBJECTIVES Comparison of sapheno-femoral ligation and stripping ( SFL/S ) versus endovenous laser ablation ( EVLA , 980-nm ) in the treatment of great saphenous vein ( GSV ) insufficiency , using local tumescent anaesthesia . DESIGN R and omised , single centre trial . MATERIAL S AND METHODS Patients with GSV incompetence and varicose veins were r and omised to either SFL/S or EVLA . At days 1 , 2 , 3 , 7 , 10 , and 14 post-treatment , patients completed question naires on pain and quality of life . Recurrent varicose veins were evaluated by Duplex ultrasound ( DUS ) performed at 1 and 6 weeks , and 6 and 12 months . RESULTS 130 legs in 121 patients were treated by SFL/S ( n=68 ) or EVLA ( n=62 ) . Significantly more post-treatment pain was noted after EVLA at days 7 , 10 and 14 ( p<0.01 ; p<0.01 ; p=0.01 ) , more hindrance in mobility at days 7 ( p<0.01 ) and 10 ( p=0.01 ) , and in self care ( p=0.03 ) and daily activities ( p=0.01 ) at day 7 compared to SFL/S. DUS at 1-year follow-up showed 9 % recurrences ( 5/56 ) after EVLA and 10 % ( 5/49 ) after SFL/S. CONCLUSION Both SFL/S and EVLA , using local tumescent anaesthesia , were well tolerated , with no difference in short-term recurrence rate . In the second week after EVLA , patients experienced significantly more pain result ing in restricted mobility , self care and daily activity compared to Introduction : Chronic venous insufficiency is the most common vascular disease in the adult population . However , r and omized clinical trials ( RCTs ) comparing therapeutic options are limited . Patients and Methods : A total of 180 patients with saphenofemoral junction and great saphenous reflux detected on duplex were r and omized to either ultrasound-guided radiofrequency ablation ( RFA ) or st and ard surgical treatment . The study participants blindly chose an assignment card that placed them in either group A ( ultrasound-guided RFA of the great saphenous vein [ GSV ] ; n = 90 ) ; or group B ( surgical management n = 90 ) . Patients were followed up for 24 months . Results : The primary occlusion rate in group A was 94.5 % versus 100 % in group B. Radiofrequency ablation had a lower overall complication rate ( P = .02 ) and shorter post-intervention hospital stay ( P = .001 ) . Kaplan-Meier analysis showed no significant differences in recurrence rates at 24 months follow-up ( P = .45 ) . Radiofrequency ablation was significantly more expensive ( P = .003 ) . Conclusion : Great saphenous vein occlusion was achieved efficiently in 94 % of our group using RFA with minimal complications and obvious advantages as compared to st and ard surgery INTRODUCTION This study compares the outcome 3 years after treatment of varicose veins by endovenous laser ablation ( EVLA ) , radiofrequency ablation , ultrasound-guided foam sclerotherapy ( UGFS ) , or surgery by assessing recurrence , Venous Clinical Severity Score ( VCSS ) , and quality of life ( QOL ) . METHODS A total of 500 patients ( 580 legs ) were r and omized to one of the three endovenous treatments or high ligation and stripping of the great saphenous vein ( GSV ) . Follow-up included clinical and duplex ultrasound examinations and VCSS and QOL question naires . Kaplan-Meier ( KM ) life-table analysis was used . P values below .05 were considered statistically significant . RESULTS At 3 years , eight ( KM estimate , 7 % ) , eight ( KM estimate , 6.8 % ) , 31 ( KM estimate , 26.4 % ) , and eight ( KM estimate , 6.5 % ) of GSVs recanalized or had a failed stripping procedure ( more than 10 cm open refluxing part of the treated GSV ; CLF , EVLA , UGFS , and stripping , respectively ; P < .01 ) . Seventeen ( KM estimate , 14.9 % ) , 24 ( KM estimate , 20 % ) , 20 ( KM estimate , 19.1 % ) , and 22 ( KM estimate , 20.2 % ) legs developed recurrent varicose veins ( P = NS ) . The patterns of reflux and location of recurrent varicose veins were not different between the groups . Within 3 years after treatment , 12 ( KM estimate , 11.1 % ) , 14 ( KM estimate , 12.5 % ) , 37 ( KM estimate , 31.6 % ) , and 18 ( KM estimate , 15.5 % ) legs were retreated in the CLF , EVLA , UGFS , and stripping groups , respectively ( P < .01 ) . VCSS , SF-36 , and Aberdeen QOL scores improved significantly in all the groups with no difference between the groups . CONCLUSIONS All treatment modalities were efficacious and result ed in a similar improvement in VCSS and QOL . However , more recanalization and reoperations were seen after UGFS Endovenous laser ablation ( EVLA ) is a popular minimally invasive treatment for varicose veins . Surgical treatment , featuring junctional ligation and inversion stripping , has shown excellent clinical and cost effectiveness . The clinical effectiveness of both treatments was compared within a r and omized trial BACKGROUND Great saphenous vein ( GSV ) incompetence is the most common cause of superficial venous insufficiency . Radiofrequency catheter ablation ( RFA ) is superior to conventional ligation and stripping , and endovenous laser treatment ( EVL ) has emerged as an effective alternative to RFA . This r and omized study evaluated RFA and EVL for superficial venous insufficiency due to GSV incompetence and compared early and 1-year results . METHODS Between June 2006 and May 2008 , patients with symptomatic primary venous insufficiency due to GSV incompetence were r and omized to RFA or EVL . Patients with bilateral disease were r and omized for treatment of the first leg and received the alternative method on the other . Pretreatment examination included a leg assessment using the Venous Clinical Severity Score ( VCSS ) and CEAP classification . Patients completed the Chronic Venous Insufficiency Question naire 2 ( CIVIQ2 ) . RFA was performed with the ClosurePlus system ( VNUS Medical Technologies , Sunnyvale , Calif ) . EVL was performed with the EVLT system ( AngioDynamics Inc , Queensbury , NY ) . Early ( 1-week and 1-month ) postoperative results of pain , bruising , erythema , and hematoma were recorded . Duplex ultrasound ( DU ) imaging was used at 1 week and 1 year to evaluate vein status . VCSS scores and CEAP clinical class were recorded at each postoperative visit , and quality of life ( QOL ) using CIVIQ2 was assessed at 1 month and 1 year . RESULTS The study enrolled 118 patients ( 141 limbs ) : 46 ( 39 % ) were r and omized to RFA and 48 ( 40 % ) to EVL , and 24 ( 20 % ) had bilateral GSV incompetence . At 1 week , one patient in the RFA group had an open GSV and was deemed a failure . More bruising occurred in the EVL group ( P = .01 ) at 1 week , but at 1 month , there was no difference in bruising between groups . At 1 year , DU imaging showed evidence of recanalization with reflux in 11 RFA and 2 EVL patients ( P = .002 ) . The mean VCSS score change from baseline to 1 week postprocedure was higher for RFA than EVL ( P = .002 ) , but there was no difference between groups at 1 month ( P = .07 ) and 1 year ( P = .9 ) . Overall QOL mean score improved over time for all patients ( P < .001 ) . CEAP clinical class scores of > or=3 were recorded in 21 RFA ( 44 % ) and 24 EVL patients ( 44 % ) pretreatment , but at 1-year , 9 RFA ( 19 % ) and 12 EVL patients ( 24 % ) had scores of > or=3 ( P < .001 ) . This represented a significant improvement in all patients compared with baseline . CONCLUSION Both methods of endovenous ablation effectively reduce symptoms of superficial venous insufficiency . EVL is associated with greater bruising and discomfort in the perioperative period but may provide a more secure closure over the long-term than RFA OBJECTIVE To evaluate therapeutic results of endovenous radiofrequency in combination with TriVex in treatment of venous insufficiency in lower extremities . METHODS One hundred and fifty patients with chronic venous insufficiency ( 150 limbs ) were r and omly assigned to Group A ( 75 limbs ) and Group B ( 75 limbs ) . Patients in Group A were treated with long saphenous veins radiofrequency ablation procedures in combination with TriVex . Patients in Group B were treated with long saphenous veins traditional stripping operation in combination with TriVex . The postoperative pain , average hospital stay and short-term results in hospital were compared between the two groups . Self- assessment of the operation 4 weeks after , changes of CEAP classification , venous clinical severity score ( VCSS ) and chronic venous insufficiency question naire ( CIVIQ ) score were compared between the two groups . RESULTS The operation time in Group A was ( 67 + /- 11 ) min , compared with ( 59 + /- 9 ) min in Group B ( P > 0.05 ) . Postoperative pain and average hospital stay in Group A were significantly lower than those in Group B ( P < 0.05 ) . The scores of self- assessment of the operation in Group A was higher than that in Group B 4 weeks after operation ( P < 0.05 ) . The change of CEAP classification , VCSS and quality of life were significant after operation in both groups . The VCSS of Group A decreased by 4.6 + /- 2.5 compared with 4.3 + /- 2.7 in Group B ( P > 0.05 ) . CONCLUSIONS Endovenous radiofrequency combined with TriVex for treatment of venous insufficiency in lower extremity is available , effective and with less trauma and faster recovery . CEAP classification , VCSS and CIVIQ are useful tools for assessing outcomes after radiofrequency in these patients OBJECTIVE The aim of this r and omized study was to compare a new method of endovenous saphenous vein obliteration ( Closure System , VNUS Medical Technologies , Inc , Sunnyvale , Calif ) with the conventional stripping operation in terms of short-term recovery and costs . METHODS Twenty-eight selected patients for operative treatment of primary greater saphenous vein tributary varicose veins were r and omly assigned to endovenous obliteration ( n = 15 ) or stripping operation ( n = 13 ) . Postoperative pain was daily assessed during the 1st week and on the 14th postoperative day . The length of sick leave was determined . The R AND -36 health survey was used to assess the patient health-related quality of life . The patient conditions were controlled 7 to 8 weeks after surgery , and patients underwent examination with duplex ultrasonography . The comparison of costs included both direct medical costs and costs result ing from lost of productivity of the patients . Costs that were similar in the study groups were not considered in the analysis . RESULTS All operations were successful , and the complication rates were similar in the two groups . Postoperative average pain was significantly less severe in the endovenous obliteration group as compared with the stripping group ( at rest : 0.7 , st and ard deviation [ SD ] 0.5 , versus 1.7 , SD 1.3 , P = .017 ; on st and ing : 1.3 , SD 0.7 , versus 2.6 , SD 1.9 , P = .026 ; on walking : 1.8 , SD 0.8 , versus 3.0 , SD 1.8 , P = .036 ; with t test ) . The sick leaves were significantly shorter in the endovenous obliteration group ( 6.5 days , SD 3.3 days , versus 15.6 days , SD 6.0 days ; 95 % CI , 5.4 to 12.9 ; P < .001 , with t test ) . Physical function was also restored faster in the endovenous obliteration group . The estimated annual investment costs of the closure operation were US $ 3360 . The other direct medical costs of the Closure operation were about $ 850 , and those of the conventional treatment were $ 360 . With inclusion of the value of the lost working days , the Closure treatment was cost-saving for society , and when 40 % of the patients are retired ( or 60 % of the productivity loss was included ) , the Closure procedure became cost-saving at a level of 43 operations per year . CONCLUSION Endovenous obliteration may offer advantages over the conventional stripping operation in terms of reduced postoperative pain , shorter sick leaves , and faster return to normal activities , and it appears to be cost-saving for society , especially among employed patients . Because the procedure is also associated with shorter convalescence , this new method may potentially replace conventional varicose vein surgery Background There has been considerable concern expressed about the outcomes achieved in Independent Sector Treatment Centres ( ISTCs ) introduced in Engl and since 2003 . Our aim was to compare the case-mix and patients ' reported outcomes of surgery in ISTCs and in NHS providers . Methods Prospect i ve cohort study of 769 patients treated in six ISTCs and 1895 treated in 20 NHS providers ( acute hospitals and treatment centres ) in Engl and during 2006–07 . Participants underwent one of three day surgery procedures ( inguinal hernia repair , varicose vein surgery , cataract extraction ) or hip or knee replacement . Change in patient-reported health status and health related quality of life ( measured using a disease-specific and a generic ( EQ-5D ) instrument ) was assessed either 3-months ( day surgery ) or 6-months ( hip/knee ) after surgery . In addition patient-reported post-operative complications and an overall assessment of success of surgery were collected . Outcome measures were adjusted ( using multivariable regression ) for patient characteristics ( disease severity , duration of symptoms , age , sex , socioeconomic status , general health , previous similar surgery , comorbidity ) . Results Post-operative response rates varied by procedure ( 73%–88 % ) and were similar for those treated in ISTCs and NHS facilities . Patients treated in ISTCs were healthier , were less likely to have any comorbidity and , for those undergoing cataract surgery or joint replacement , their primary condition was less severe . Those undergoing hernia repair or joint replacement were less likely to have had similar surgery before . When adjustment was made for pre-operative characteristics , patients undergoing cataract surgery or hip replacement in ISTCs achieved a slightly greater improvement in functional status and quality of life than those treated in NHS facilities , while the opposite was true of patients undergoing hernia repair . No significant differences were found for the two other procedures . Patients treated in ISTCs were less likely to report post-operative problems than those treated in NHS facilities for cataract surgery ( Adjusted Odds Ratio 0.35 ; 95 % CI 0.17–0.70 ) , hernia repair ( 0.42 ; 0.28–0.63 ) and knee replacement ( 0.44 ; 0.28–0.69 ) . Most patients described the result of their operation as excellent , very good or good , regardless of where they were treated . Conclusion The case-mix of patients treated in ISTCs differs from that in NHS providers , in line with the intention of the contracts . Caution is needed in interpreting the observation that patients treated in ISTCs reported slightly better outcomes as very few ISTCs participated , case-mix adjustment might have been insufficient , and patients ' reports might have been biased as they were more likely to be satisfied with the way they were treated BACKGROUND Endovascular radiofrequency obliteration has been used as an alternative to conventional vein-stripping surgery for elimination of saphenous vein insufficiency . A clinical registry was established in 1998 , and its mid-term results have been reported previously . This study is to demonstrate the long-term treatment outcomes and to determine the risk factors that affect treatment efficacy . METHODS Data were collected in an ongoing multicenter , prospect i ve registry . Patients were treated before October 2004 . Clinical and duplex ultrasound follow-up was performed 1 week , 6 months , 1 year , and yearly thereafter to 5 years . Treatment efficacy and clinical improvement after the procedure were analyzed . Three types of anatomical failure were identified . Logistic regression analysis was performed to determine the existence of any significant risk factors associated with anatomical failure . Risk factors considered were age , gender , body mass index , vein diameter , and pullback speed . The impact of anatomical failure on clinical symptoms and varicose vein recurrence was also analyzed . RESULTS There were 1,006 patients ( 1,222 limbs ) treated , their mean age was 47.4 + /- 12.1 years , and 78.1 % were female . Veins treated included 89.1 % great saphenous vein above-knee segments , 1.2 % great saphenous vein below-knee segments , 4.1 % great saphenous vein groin-to-ankle , 4.3 % small saphenous veins , and 1.3 % accessory saphenous veins . Mean vein diameter was 7.5 mm , with a maximum of 24 mm . Vein occlusion rates were 87.1 % , 88.2 % , 83.5 % , 84.9 % , and 87.2 % , and reflux-free rates were 88.2 % , 88.2 % , 88.0 % , 86.6 % , and 83.8 % at each annual follow-up . Clinical symptom improvement was seen in 70 % to 80 % of limbs with anatomical failures and in 85 % to 94 % of limbs with anatomical success from 6 months to 5 years after the radiofrequency obliteration . Logistic regression analysis showed that catheter pullback speed ( P < .0001 ) and body mass index ( P < .0333 ) were risk factors for anatomical failure . Limbs that had type II and type III anatomical failures were found to be more prone to varicose vein recurrence . CONCLUSIONS Endovascular radiofrequency obliteration of saphenous vein reflux exhibits enduring efficacy . Adequate pullback speed during the procedure should be emphasized to ensure the proper thermal dose delivery . A whole treatment strategy to address hemodynamically significant tributaries and perforators can further improve treatment outcomes . Body mass index is a risk factor for anatomical failure , indicating the impact of hemodynamic factors on disease progression and recurrence This report describes the clinical effectiveness and recurrence rates from a r and omized trial of endovenous laser ablation ( EVLA ) and surgery for varicose veins OBJECTIVES There have been few r and omised studies comparing Radiofrequency Ablation(RFA ) with other endovenous techniques . The primary aim of this study was to determine whether RFA of the great saphenous vein ( GSV ) was associated with less pain and bruising than endovenous laser ablation ( EVLA ) . MATERIAL S AND METHODS This trial had two cohorts-- patients with bilateral GSV incompetence causing varicose veins ( VV ) and those with unilateral GSV VVs . In total 87 legs were treated in this study . Limbs in the bilateral group were treated with RFA in one leg and EVLA in the other . In the unilateral group limbs were r and omised to RFA or EVLA . RFA was performed using the Celon RFiTT system ( Teltow , Germany ) . EVLA was performed using an 810 nm Laser ( Biolitec AG , Germany ) . Phlebectomies were performed as required . Primary endpoints were patient assessed pain and bruising measured by visual analogue scale ( VAS ) . Secondary endpoints were patency assessed by duplex ultrasound at 6 weeks and 6 months . RESULTS In the bilateral group , RFA result ed in significantly less pain than EVLA on days 2 - 11 postoperatively . RFA also result ed in significantly less bruising than EVLA on days 3 - 9 . There were no significant differences in mean post operative pain , bruising and activity scores in the unilateral group . Both RFA and EVLA result ed in occlusion rates of 95 % at 10 days postoperatively . CONCLUSIONS RFA was less painful for patients than EVLA and produced less bruising in the postoperative period with comparable success rates but there was no difference in the unilateral group AIM To assess the safety and efficacy of sclerotherapy of the great saphenous vein ( GSV ) comparing st and ardised polidocanol foam to liquid polidocanol in a r and omised controlled trial ( RCT ) . METHODS A multicentre r and omised controlled clinical trial was carried out in which saphenous trunks were treated by sclerotherapy . 106 patients with primary varicose veins due to an incompetent GSV were treated with either st and ardised 3 % polidocanol foam or 3 % liquid polidocanol . The primary efficacy criterion was elimination of reflux ( < 0.5 sec ) measured 3 cm below the sapheno-femoral junction ( SFJ ) by duplex ultrasonography 3 months after the last injection . RESULTS A significantly greater number of patients were successfully treated by foam sclerotherapy result ing in 69 % elimination of reflux compared to 27 % patients treated with liquid sclerosant . The secondary endpoints of vein occlusion , reflux time , refilling time and patient satisfaction also improved significantly more in the foam group . The mean number of treatment sessions was 1.3 in the foam group compared to 1.6 in the liquid group . Differences between study centres occurred with a mean of 96 % reflux elimination in 6 centres versus 39 % in 4 other centres . Centres with a high response rate injected a higher mean volume ( 4.3 vs. 3.6 ml ) in the first session in a vein with a smaller diameter ( 7.5 mm vs. 8.4 mm ) . No difference in adverse drug reactions was observed between treatment groups . CONCLUSIONS St and ardised 3 % polidocanol foam is more efficient and equally safe compared to 3 % liquid polidocanol for treatment of GSV . In comparison to other studies a relatively small volume was injected into relatively large veins Endovenous laser ablation ( EVLA ) is a minimally invasive technique for treating varicose veins due to truncal vein incompetence . This r and omized trial compared EVLA with conventional surgery in patients with primary saphenofemoral and great saphenous vein ( GSV ) reflux Background : Endovenous ablation of varicose veins using radiofrequency ablation ( RFA ) and endovenous laser therapy ( EVLT ) has reported advantages over traditional open surgical treatment . There is little evidence comparing the efficacy and patient-reported outcomes between the 2 endovenous solutions . This study compares the RFA and EVLT strategies in a prospect i ve double-blind clinical trial . Methods : Consecutive patients with primary unilateral great saphenous vein ( GSV ) reflux undergoing endovenous treatment were r and omized to RFA ( VNUS ClosureFAST ) or EVLT ( 810-nm diode laser ) . The primary outcome measure was GSV occlusion at 3 months after treatment . Secondary outcome measures were occlusion at 7 days , postoperative pain , analgesic requirement , and bruising , assessed at day 7 after surgery . Quality of life ( QoL ) was assessed preoperatively and 3 months after surgery using the Aberdeen Varicose Vein Question naire ( AVVQ ) and EQ-5D . Results : A total of 159 patients were r and omized to RFA ( 79 patients ) or EVLT ( 80 patients ) . Groups were well matched for demographics , disease extent , severity , and preoperative QoL. Duplex scanning confirmed 100 % vein occlusion at 1 week in both groups . At 3 months , occlusion was 97 % for RFA and 96 % for EVLT ; P = 0.67 . Median ( interquartile range ) percentage above-knee bruise area was greater after EVLT 3.85 % ( 6.1 ) than after RFA 0.6 % ( 2 ) ; P = 0.0001 . Postoperative pain assessed at each of the first 7 postoperative days was less after RFA ( P = 0.001 ) . Changes in the AVVQ ( P = 0.12 ) and EQ-5D ( P = 0.66 ) at 3 months were similar in both groups . Conclusions : RFA and EVLT offer comparable venous occlusion rates at 3 months after treatment of primary GSV varices ; with neither modality proving superior . RFA is associated with less periprocedural pain , analgesic requirement , and bruising . Registration number : IS RCT N63135694 ( http://www.controlled-trials.com OBJECTIVE This study compared postoperative patient comfort and the surgical outcome of endovenous laser ablation ( EVLA ) or stripping of the great saphenous vein , both performed in conjunction with high ligation . METHODS The study r and omized 100 patients with primary trunk varicosities of the great saphenous vein ( CEAP clinical class II to IV ) to EVLA or stripping . The success of surgery was followed-up by duplex ultrasound imaging at 1 , 4 , and 16 weeks . Primary end points were the size of the hematoma 1 week after the operation and the preoperative disease-specific Chronic Venous Insufficiency Question naire ( CIVIQ ) quality of life score compared with 4 weeks postoperatively . Secondary end points were postoperative symptoms ( pain , use of analgesics , paresthesia at the ankle , residual hematoma ) , complications , time taken to resume work , the patient 's satisfaction with the cosmetic outcome , and the CIVIQ quality of life score at 16 weeks . RESULTS The groups were well matched at baseline . In all , 95 patients could be followed up in accordance with the protocol . The treatment was successful in all patients . Endovenous laser ablation was associated with an occlusion rate of 100 % . Hematomas were significantly smaller after EVLA ( median [ quartiles ] ) at 125 ( 55 - 180 ) cm(2 ) vs stripping 200 ( 123 - 269 ) cm(2 ) ( P = .001 ) . No difference was registered between groups for the CIVIQ quality of life score , with EVLA at -1.25 ( -7.5 - 11.25 ) vs stripping at 4.38 ( -5.94 - 14.38 ; P = .34 ) . Several postoperative symptoms favored EVLA , but the only significant differences were seen in the minor side effects of surgery at 1 and 4 weeks and discomfort due to paresthesia at the ankle in the first postoperative week . EVLA was associated with a longer period of time until return to work ( median [ quartiles ] ) of 20 ( 14 - 25.5 ) days vs 14 ( 12.8 - 25 ) days ( P = .054 ) . CONCLUSION Endovenous laser ablation combined with high ligation is safe and effective . Postoperative hematomas are significantly smaller than those after stripping . Short-term quality of life is at least as good as that after stripping . The long-term results warrant further investigation This was the long‐term follow‐up of a previously reported r and omized clinical trial comparing endovenous laser ablation ( EVLA ) with cryostripping for great saphenous varicose veins OBJECTIVE to compare the clinical outcome of foam sclerotherapy of the great saphenous vein ( GSV ) combined with sapheno-femoral junction ( SFJ ) ligation to st and ard stripping surgery . METHODS as a prospect i ve r and omized controlled trial , 60 consecutive patients with incompetence of the GSV result ing in varicose veins were prospect ively r and omized into 2 groups , treated by SFJ ligation and either foam sclerotherapy or st and ard stripping of the GSV . There were 26 male and 34 female with a median age of 49 years ( ranging 37 to 66 years ) . Primary end points were patient recovery period , postoperative pain , quality of life and recurrence rate . Secondary end points were frequency of complications on the two arms of the trial . RESULTS all treatments were completed as intended . The time taken to complete treatment was shorter in the foam sclerotherapy plus SFJ ligation group than the st and ard stripping ( 43 min vs. 65 min , P < 0.01 ) . Less analgesic use postoperatively was recorded in the foam sclerotherapy group . Median time to return to normal activities was significantly reduced in the foam sclerotherapy group compared to the surgical group ( 3 d vs. 6 d , P < 0.01 ) . After 3 months , median CEAP class dropped from four pre-operatively to one following treatment in both groups ( P < 0.01 ) . After 6 months , in the foam sclerotherapy group , 5 patients needed further sessions of foam sclerotherapy , result ing in a short-term closure rate of 80.0 % . And the short-term obliteration rate was 89.5 % in the conventional surgery group . CONCLUSIONS foam sclerotherapy combined with sapheno-femoral ligation involves a shorter treatment time , less postoperative discomfort and results in more rapid recovery compared to conventional GSV stripping OBJECTIVE This study aim ed to assess the outcome of endoluminal thermal ablation ( VNUS ) and traditional redo groin surgery ( RGS ) and long saphenous vein ( LSV ) stripping in patients with bilateral recurrent long saphenous varicose veins . METHODS This was a r and omised patient controlled double blind study . Sample size calculations required 16 patients . Their median age was 54 and 11 were women . The median CEAP class was 3 . At operation one leg , chosen at r and om , was treated with VNUS and avulsions using intra-operative duplex control . The other leg was treated with traditional RGS , exposure of the femoral vein , stripping of the LSV and multiple avulsions . Post-operatively patients completed 10 cm visual analogue scales for pain and bruising . Digital Image analysis was used to objective ly assess bruising . Statistical analysis was done using Wilcoxon signed rank test for paired data . Results are expressed as median values ( inter-quartile ranges ) . RESULTS Time to perform VNUS was 25.5 ( 20.5 - 31.3 ) min compared with 40 ( 34.5 - 45.5 ) min it took for RGS ( p=0.02 ) . Pain score for VNUS was 1.7 ( 0.2 - 4 ) , significantly lower than that for RGS 3.8 ( 0.6 - 6.3 ) ( p=0.02 ) . Bruise score for VNUS was 1.7 ( 0.4 - 4.4 ) , and that for RGS was 5.2 ( 2.6 - 7 ) ( p=0.03 ) . All LSVs were sealed by VNUS at duplex follow up . Three legs in the RGS group and two in the VNUS group had a minor complication . CONCLUSIONS VNUS caused less pain and bruising and was performed more quickly than RGS . VNUS should be considered the treatment of choice for recurrent long saphenous varicose veins PURPOSE This study was design ed as a prospect i ve multicenter r and omized comparison of procedure-related complications , patient recuperation , and quality -of-life outcomes between patients undergoing vein stripping with high ligation and patients undergoing great saphenous vein ( GSV ) obliteration with temperature-controlled radiofrequency ablation without adjunctive high ligation ( Closure procedure ) . METHODS Eighty-five patients ( 86 limbs ) from five sites ( France , 2 ; Austria , 1 ; United States , 2 ) were r and omly allocated to undergo radiofrequency obliteration ( RFO ) or stripping and high ligation ( S&L ) . Final analysis included data for 44 limbs in the RFO group and 36 limbs in the S&L group . Follow-up examinations were performed at 72 hours , 1 week , 3 weeks , and 4 months . All patients completed the CIVIQ2 quality -of-life ( QOL ) question naire and underwent clinical and ultrasound examinations at each follow-up visit . RESULTS Immediate success on the day of treatment was reported for 95 % ( 42 of 44 ) of limbs in the RFO group and 100 % ( 36 of 36 ) of limbs in the S&L group . In seven RFO limbs ( 16.3 % ) a scan obtained 72 hours after the procedure showed flow in the proximal GSV . Five of these segments had reflux in the open segment . At 1 week two of these closed , and an additional segment closed at 3 weeks . In no cases did flow reappear after complete occlusion of the GSV . Time to return to normal activities was significantly less in the RFO group ( mean , 1.15 days ; 95 % confidence interval [ CI ] , 0.05 - 2.34 ) compared with the S&L group ( mean , 3.89 days ; CI , 2.67 - 5.12 ; P = .02 ) . In the RFO group , 80.5 % of patients returned to routine activities of daily living within 1 day , compared with 46.9 % of patients in the S&L group ( P < .01 ) . Patients in the RFO group were able to return to work in 4.7 days ( CI , 1.16 - 8.17 ) , compared with 12.4 days ( CI , 8.66 - 16.23 ) for the S&L group ( P < .05 ) . Analysis of the QOL surveys showed statistically significant differences in favor of the RFO group for global score and pain score during follow-up . The magnitude of the difference , however , progressively decreased between 1 week and 4 months . CONCLUSIONS In the absence of significant complications , such as deep vein thrombosis and pulmonary embolism , severe neuritic sequelae , and skin burns , there are significant early advantages to endovascular obliteration of the GSV compared with conventional vein stripping BACKGROUND Foamed sclerosing agents have been used with enthusiasm by phlebologists for more than 5 decades . Any type of varicose veins can and has been treated with this technique . Numerous publications have stressed the advantages of foamed sclerosing agents on the basis of empiric and experimental criteria and have described various individual techniques to prepare foams . Until now , however , no comparative study for the treatment of large varicose veins with foam or liquid exists . OBJECTIVE The purpose of this first r and omized , prospect i ve , multicenter trial was to study the elimination of reflux , the rate of recanalization , and possible side effects of foam sclerotherapy ( FS ) compared with conventional liquid sclerotherapy for the greater saphenous vein ( GSV ) . METHODS Eighty-eight patients were r and omized into two groups : One group was treated with sclerosing foam ( 45 patients ) and the other with sclerosing liquid ( 43 cases ) . Sclerotherapy was performed with direct puncture of the vessel under duplex guidance . The reference sclerosing agent was polidocanol in a 3 % solution . The foam was prepared using the Double Syringe System ( DSS ) method . Only one injection of 2.0 or 2.5 mL liquid or foam was allowed , depending on the diameter of the GSV . Results were assessed according to the protocol . RESULTS Follow-up after 3 weeks showed 84 % elimination of reflux in the GSV with DSS foam versus 40 % with liquid sclerosant ( P < 0.01 ) . At 6 months , six recanalizations were found in the liquid group versus two in the foam group . After 1 year , no additional recanalization was observed with either foam or liquid . Longer term studies are underway . Side effects did not differ between both groups . CONCLUSION The efficacy of sclerosing foam ( DSS ) compared with sclerosing liquid in therapy of the GSV is superior , a finding that had already gained empirical recognition but for which there has not been any clinical evidence to date OBJECTIVE To compare the costs involved ( from procedure to recovery ) following radiofrequency ablation and conventional surgery for lower limb varicose veins in a selected population . DESIGN Prospect i ve r and omised controlled trial . METHODS Patients with symptomatic great saphenous varicose veins suitable for radiofrequency ablation were r and omised to either RF ablation or surgery ( sapheno-femoral ligation and stripping ) . The hospital , general practice and patient costs incurred until full recovery and the indirect cost to society , due to sickness leave after surgery , were calculated to indicate mean cost per patient under each category . RESULTS Ninety three patients were r and omised . Eighty eight patients ( 47 - RF ablation , 41 - surgery ) underwent the allocated intervention . Ablation took longer to perform than surgery ( mean 76.8 vs 47.0 min , p<.001 ) . Ablation was more expensive ( mean hospital cost per patient 1275.90 pounds vs 559.13 pounds ) but enabled patients to return to work 1 week earlier than after surgery ( mean 12.2 vs 19.8 days , p=0.006 ) . Based on the Annual Survey of Hours and Earnings ( Office of National Statistics , UK ) for full time employees , the cost per working hour gained after ablation was 6.94 pounds ( 95 % CI 6.26 , 7.62 ) . CONCLUSION The increased cost of radiofrequency ablation is partly offset by a quicker return to work in the employed group ( IS RCT N29015169http://www.controlled-trials.com ) Background Patients with varicose veins seek medical assistance for many reasons , including esthetic ones . The development of suitable and more flexible instruments , along with less invasive techniques , enables the establishment of new therapeutic procedures . Objective To compare endovenous great saphenous vein photocoagulation with an 810 nm diode laser and the conventional stripping operation in the same patient . Methods Twenty patients selected for operative treatment of primary great saphenous vein insufficiency on duplex scanning were assigned to a bilateral r and om comparison . In all cases , both techniques were performed , one on each lower limb . Clinical ly , evaluation was assessed on the seventh , thirtieth , and sixtieth postoperative days . Patients underwent examination with duplex ultrasonography and air plethysmography during the follow-up . Results Patients who received endovenous photocoagulation presented with the same pain but fewer swellings and less bruising than the stripping side . Most patients indicated that the limb operated on by laser received more benefits than the other . There was only one recanalization and no adverse effects . The venous filling time showed better hemodynamics in both techniques . Conclusion The endovenous great saphenous vein photocoagulation is safe and well tolerated and presents results comparable to those of conventional stripping BACKGROUND Endovenous laser therapy ( EVLT ) for ablation of the great saphenous vein ( GSV ) is thought to minimize postoperative morbidity compared with high ligation and stripping ( HL/S ) . Only a few r and omized trials have reported early results . This prospect i ve r and omized trial compared EVLT ( 980 nm ) and HL/S results at 1 and 2 years after the intervention . METHOD Patients with symptomatic varicose veins due to GSV insufficiency were r and omized to HL/S ( 100 limbs ) or EVLT ( 104 limbs ) . Four EVLT procedures failed primarily and were excluded . Phlebectomy and ligature of incompetent perforators were performed whenever indicated in both groups . Patients were re-examined clinical ly and by duplex ultrasound imaging preoperatively and at 12 days and at 1 and 2 years after treatment . Closure rate , complication rate , time to return to normal activity , the Aberdeen Varicose Vein Symptom Severity Score ( AVVSS ) , the Varicose Venous Clinical Severity Score ( VVCSS ) , and the Medical Outcome Study Short Form-36 scores were also recorded . RESULTS There were no differences in patient demographics , CEAP class , Widmer class , or severity scores between the groups . Simultaneous interventions did not differ between the groups . Similar times for the return to normal activity and scores for postoperative pain were reported . No major complications after treatment were recorded . HL/S limbs had significantly more postoperative hematomas than EVLT limbs , and EVLT patients reported more bruising . Follow-up at 1 year was 100 % for HL/S and 99 % for EVLT . Two GSVs in the EVLT group reopened and three partially reopened . No open GSVs occurred in HL/S limbs . Ninety-eight percent of the limbs in both groups were free of symptoms . VCSS , AVVSS , and Short Form-36 scores did not reveal any group differences . At 2 years , no differences compared with 1-year results were observed , except that two more GSVs in the EVLT group were partially reopened . CONCLUSIONS Abolition of GSV reflux and improvement in quality of life was similar after HL/S and EVLT . After EVLT , however , two GSVs were found completely reopened and five were partially reopened , which was significantly higher than after HL/S. A prolonged follow-up is ongoing We evaluated the 3-year outcome of a series of patients with primary varicose veins who were r and omized to radiofrequency endovenous obliteration vs. stripping of the long saphenous vein ( LSV ) . Twenty-eight patients were included in the study : 15 were r and omized to the radiofrequency endovenous obliteration procedure and 13 to LSV stripping . At 3-year follow-up , five patients ( 33.3 % ) of the endovenous group had recurrent or residual varices and in three of them a reflux in the thigh veins was detected . None of the primarily occluded LSV segments was recanalized . In the stripping group , three patients ( 23.1 % , p = 0.68 ) showed varicosities at clinical and duplex examinations . In one patient , a patent duplicate LSV trunk was detected . In the remaining two patients , no reflux in the thigh region was detected . According to the present results , radiofrequency endovenous obliteration of the LSV is associated with somewhat poorer short-term results compared with the stripping operation This prospect i ve r and omized study compared the treatment of greater saphenous vein insufficiency by stripping and local avulsions of varicose veins with high ligation of the saphenofemoral junction ( crossectomy ) combined with sclerocompression therapy . Of 156 consecutive patients , 89 legs were r and omly allocated to stripping and 92 to high ligation . At follow-up of 3 months and 1 , 2 , and 3 years after treatment , clinical and Doppler ultrasound results , and complaints and cosmetic results , as judged by the patient and the surgeon , were scored . At 3 years , 69 limbs in the stripping group ( 78 % ) and 73 limbs in the ligation group ( 79 % ) were available to follow-up . The cosmetic results , both judged by the patient and the surgeon , were significantly better ( P < 0.05 ) in the stripped limbs than in the limbs with high ligation and sclerotherapy . Clinical and Doppler ultrasound evidence of reverse flow in the saphenous vein was significantly less ( P < 0.001 ) after the stripping operation . The results of treatment of isolated saphenous vein insufficiency by stripping operation , therefore , were superior to those obtained by high ligation combined with sclerotherapy This r and omized clinical trial compared early outcomes after radiofrequency ablation ( RFA ) and conventional surgery for varicose veins OBJECTIVE This study aims to compare the outcome 2years after treatment of varicose veins by endovenous laser ablation ( EVLA ) or surgery by assessing recurrence , venous clinical severity score ( VCSS ) and quality of life . METHODS A total of 121 patients ( 137 legs ) were r and omised to either EVLA or saphenofemoral ligation and stripping of the great saphenous vein ( GSV ) . Follow-up included clinical and duplex ultrasound examinations , VCSS and quality of life question naires . RESULTS A total of 18 ( 26 % ) and 25 patients ( 37 % ) in the EVLA and surgery group , respectively , developed recurrent varicose veins ( not significant ( NS ) between groups ) . The source of reflux was not significantly different between the groups . Technical failure occurred in three EVLA and two surgery patients , reflux in the anterior accessory GSV , the groin , thigh and calf perforators was found in six , two , four , and three EVLA patients , and in three , three , nine and six surgery patients . VCSS , Aberdeen Varicose Vein Severity Score and several domains of the Medical Outcomes Study Short Form 36 ( SF36 ) quality of life score improved significantly in both groups . CONCLUSIONS No significant differences in clinical or ultrasound recurrences were found between EVLA and surgery groups . Our study also shows that similar improvements in clinical severity scores and quality of life were gained in both treatments OBJECTIVES The aim of this study was to assess different techniques of saphenofemoral ligation in the treatment of primary varicose veins . METHODS One hundred and eighty-two patients ( 210 legs ) with primary saphenofemoral junction incompetence were r and omised to st and ard saphenofemoral ligation ( transfixion with an absorbable suture ) ( SSL ) or flush saphenofemoral ligation ( oversewing with 4/0 polypropylene ) ( FSL ) . All legs underwent additional great saphenous vein stripping and multiple phlebectomies . Patients underwent assessment preoperatively , and at 6 weeks , 1 year and 2 years postoperatively with clinical examination , duplex imaging and completion of the Aberdeen Varicose Vein Symptom Severity Score ( AVVSSS ) . RESULTS A total of 148 patients ( 172 legs ) attended follow-up at 2 years postoperatively . Recurrent varicose veins were visible in 30 legs ( 33 per cent ) in the SSL group and 26 legs ( 32 per cent ) in the FSL group ( P=0.90 ) . Neovascularisation was present in 20 groins ( 22 per cent ) in the SSL group and 15 groins ( 19 per cent ) in the FSL group ( P=0.57 ) . Nine cases of neovascularisation in the SSL group and five in the FSL group directly result ed in clinical recurrence ( P=0.37 ) . CONCLUSIONS Flush ligation of the saphenofemoral junction confers no advantage over st and ard ligation with respect to clinical recurrence and neovascularisation . REGISTRATION NUMBER IS RCT N20235689 ( http://www.controlled-trials.com ) AIM This study is a prospect i ve r and omised controlled trial comparing sapheno-femoral ligation , great saphenous stripping and multiple avulsions with sapheno-femoral ligation and ultrasound guided foam sclerotherapy to the saphenous vein . Primary end points were patient recovery period and quality of life and secondary end points frequency of complications on the two arms of the trial and the cost of the treatment . MATERIAL AND METHOD Sixty patients with primary varicose veins due to GSV incompetence and suitable for day case surgery were r and omly allocated to undergo ultrasound-guided sclerotherapy with sapheno-femoral ligation under local anaesthesia ( n=30 ) or sapheno-femoral ligation , stripping and multiple avulsions under general anaesthesia ( n=30 ) . The study protocol included history , physical examination , assignment of CEAP class and assessment venous clinical severity score ( VCSS ) , completion of the aberdeen vein question naire ( AVQ ) and colour duplex ultrasound . RESULTS All treatments were completed as intended . Median time to return to normal activities was significantly reduced in the foam sclerotherapy group ( 2 days ) compared to the surgical group ( 8 days ) ( p<0.001 , Mann-Whitney ) . AVQ score was also significantly reduced at 3 months by 46 % in the sclerotherapy group , and by 40 % in the conventional surgery group ( p<0.001 , Wilcoxon ) . The time taken to complete treatment was shorter in the foam sclerotherapy plus SFJ ligation group : 45 vs. 85 min ( p<0.001 , Mann-Whitney ) . The overall cost of the procedure in the sclerotherapy group ( 672.97 pounds ) was significantly less compared to conventional surgery ( 1120.64 pounds ) . At 3 weeks , there was no statistical difference in the complication rate between the two groups . At 3 months , median CEAP class dropped from four pre-operatively to one following treatment in both groups and the median VCSS score dropped from five to one in group one and from seven to three in group two ( p<0.001 , Wilcoxon test ) . In group one four patients ( 13 % ) had a recanalised vein which needed further sessions of foam sclerotherapy , result ing in a short-term closure rate of 87 % . CONCLUSION Ultrasound guided sclerotherapy combined with sapheno-femoral ligation was less expensive , involved a shorter treatment time and result ed in more rapid recovery compared to sapheno-femoral ligation , saphenous stripping and phlebectomies This r and omized trial compared four treatments for varicose great saphenous veins ( GSVs ) . BACKGROUND The purpose of this study was to investigate the long-term outcomes following stripping of the long saphenous vein during primary varicose vein surgery and to identify factors which may predict recurrence and the need for reoperation . METHODS The original study was design ed as a r and omized trial of 100 patients ( 133 legs ) who underwent saphenofemoral ligation with or without long saphenous vein stripping . After invitation 11 years later , 51 patients ( 74 legs ) underwent clinical review and duplex imaging and completed an Aberdeen Varicose Vein Symptom Severity Score ( AVVSSS ) . The hospital notes of the original cohort of patients were used to compile cumulative data and assess predictive factors . RESULTS A cumulative total of 83 legs had developed clinical ly recurrent varicose veins by 11 years ( 62 % ) . There was no statistically significant difference between the ligation-only and the stripping groups . Reoperation was required for 20 of 69 legs that underwent ligation alone compared with 7 of 64 legs that had additional long saphenous vein stripping ( relative risk [ RR ] , 2.65 ; 95 % confidence interval , 1.20 to 5.84 ; P = .012 ) . By life table analysis , freedom from reoperation at 11 years was 70 % after ligation , compared with 86 % after stripping ( P = .01 ) . The presence of neovascularization ( RR , 2.88 ; P = .15 ) , an incompetent superficial vessel in the thigh ( RR , 3.24 ; P = .03 ) or an incompetent saphenofemoral junction on duplex imaging at 2 years postoperatively ( RR , 4.89 ; P = .0001 ) increased the risk of a patient 's developing clinical ly recurrent veins . Patients with visible recurrent varicose veins had a significantly worse AVVSSS ( P = .001 ) . CONCLUSION Stripping the long saphenous vein is recommended as part of routine varicose vein surgery as it reduced the risk of reoperation by 60 % after 11 years , although it did not reduce the rate of visible recurrent veins The aim of this r and omized single‐centre trial was to compare the 2‐year results of endovenous laser ablation ( EVLA ) and cryostripping for varicose veins OBJECTIVE To compare the relative efficacy of polidocanol ( Aetoxisclerol , Kreussler , Germany ) when used as a foam or liquid in the treatment of saphenous incompetence . MATERIAL S AND METHODS Multicentre , prospect i ve , r and omised controlled trial conducted in patients with incompetence of the great saphenous vein ( GSV ) with a truncal diameter of 4 - 8 mm . The great saphenous vein was injected using a single injection 2 - 2.5 ml of either 3 % polidocanol or sclerosant foam containing one-fifth 3 % polidocanol to four-fifths air ( DSS technique ) . Clinical assessment s and duplex ultrasound scanning were performed after 3 weeks and then every 6 months for 2 years . No re-injection was performed irrespective of the immediate result . The main outcome measure was elimination of GSV reflux . RESULTS Ninety-five patients participated in the study , 47 were r and omised to the foam sclerosant group and 48 to the liquid group . No significant difference between the 2 groups was found regarding sex , age , height , weight and saphenous vein diameter . At 3 weeks , complete elimination of reflux was obtained in 17 of the 48 patients ( 35 % ) who received liquid sclerotherapy , versus 40 of the 47 subjects ( 85 % ) in the foam group ( p<0.001 , Chi squared ) . The incidence of immediate venous spasm and the length of the sclerotic reaction , occlusion measured by echography , were significantly greater in the foam group . There was no difference in the incidence of ecchymosis , inflammatory reactions or other side effects . Follow-up of 6 , 12 , 18 and 24 months confirms our early results published in 2003 . In total only 5 patients were lost to follow-up at 2 years ( all of them were in foam group ) . These patients were included in the final outcome analysis as treatment failures ( success rates at 2 years : 53 % in foam group and 12 % in liquid group ) . CONCLUSION The sclerosant foam used in this study was more than twice as effective as the liquid from which the foam was prepared |
1,287 | 24,443,033 | The frequency of other adverse events is probably similar with both combinations ( moderate quality evidence ) .
DHA‐P is associated with less nausea , vomiting , dizziness , sleeplessness , and palpitations compared to artesunate plus mefloquine ( moderate quality evidence ) .
DHA‐P was associated with more frequent prolongation of the QTc interval ( low quality evidence ) , but no cardiac arrhythmias were reported .
In Asia , dihydroartemisinin‐piperaquine is as effective as artesunate plus mefloquine , and is better tolerated | Background The World Health Organization ( WHO ) recommends Artemisinin‐based Combination Therapy ( ACT ) for treating uncomplicated Plasmodium falciparum malaria .
This review aims to assist the decision‐making of malaria control programmes by providing an overview of the relative effects of dihydroartemisinin‐piperaquine ( DHA‐P ) versus other recommended ACTs .
Objectives To evaluate the effectiveness and safety of DHA‐P compared to other ACTs for treating uncomplicated P. falciparum malaria in adults and children . | Background Artemether-lumefantrine ( AL ) was adopted as first-line treatment for uncomplicated malaria in Kenya in 2006 . Monitoring drug efficacy at regular intervals is essential to prevent unnecessary morbidity and mortality . The efficacy of AL and dihydroartemisinin-piperaquine ( DP ) were evaluated for the treatment of uncomplicated malaria in children aged six to 59 months in western Kenya . Methods From October 2010 to August 2011 , children with fever or history of fever with uncomplicated Plasmodium falciparum mono-infection were enrolled in an in vivo efficacy trial in accordance with World Health Organization ( WHO ) guidelines . The children were r and omized to treatment with a three-day course of AL or DP and efficacy outcomes were measured at 28 and 42 days after treatment initiation . Results A total of 137 children were enrolled in each treatment arm . There were no early treatment failures and all children except one had cleared parasites by day 3 . Polymerase chain reaction (PCR)-uncorrected adequate clinical and parasitological response rate ( ACPR ) was 61 % in the AL arm and 83 % in the DP arm at day 28 ( p = 0.001 ) . PCR-corrected ACPR at day 28 was 97 % in the AL group and 99 % in the DP group , and it was 96 % in both arms at day 42 . Conclusions AL and DP remain efficacious for the treatment of uncomplicated malaria among children in western Kenya . The longer half-life of piperaquine relative to lumefantrine may provide a prophylactic effect , accounting for the lower rate of re-infection in the first 28 days after treatment in the DP arm Background Co-infection with malaria and intestinal parasites such as Ascaris lumbricoides is common . Malaria parasites induce a pro-inflammatory immune response that contributes to the pathogenic sequelae , such as malarial anaemia , that occur in malaria infection . Ascaris is known to create an anti-inflammatory immune environment which could , in theory , counteract the anti-malarial inflammatory immune response , minimizing the severity of malarial anaemia . This study examined whether Ascaris co-infection can minimize the severity of malarial anaemia . Methods Data from a r and omized controlled trial on the effect of antihelminthic treatment in Nigerian preschool-aged ( 6–59 months ) children conducted in 2006–2007 were analysed to examine the effect of malaria and Ascaris co-infection on anaemia severity . Children were enrolled and tested for malaria , helminths and anaemia at baseline , four , and eight months . Six hundred and ninety subjects were analysed in this study . Generalized linear mixed models were used to assess the relationship between infection status and Ascaris and Plasmodium parasite intensity on severity of anaemia , defined as a haemoglobin less than 11 g/dL. Results Malaria prevalence ranged from 35 - 78 % over the course of this study . Of the malaria-infected children , 55 % were co-infected with Ascaris at baseline , 60 % were co-infected four months later and 48 % were co-infected eight months later , underlining the persistent prevalence of malaria-nematode co-infections in this population . Over the course of the study the percentage of anaemic subjects in the population ranged between 84 % at baseline and 77 % at the eight-month time point . The odds of being anaemic were four to five times higher in children infected with malaria compared to those without malaria . Ascaris infection alone did not increase the odds of being anaemic , indicating that malaria was the main cause of anaemia in this population . There was no significant difference in the severity of anaemia between children singly infected with malaria and co-infected with malaria and Ascaris . Conclusion In this cohort of Nigerian preschool children , malaria infection was the major contributor to anaemia status . Ascaris co-infection neither exacerbated nor ameliorated the severity of malarial anaemia BACKGROUND Antimalarial drug resistance is now well established in both Plasmodium falciparum and Plasmodium vivax . In southern Papua , Indonesia , where both strains of plasmodia coexist , we have been conducting a series of studies to optimize treatment strategies . METHODS We conducted a r and omized trial that compared the efficacy and safety of dihydroartemisinin-piperaquine ( DHP ) with artesunate-amodiaquine ( AAQ ) . The primary end point was the overall cumulative parasitological failure rate at day 42 . RESULTS Of the 334 patients in the evaluable patient population , 185 were infected with P. falciparum , 80 were infected with P. vivax , and 69 were infected with both species . The overall parasitological failure rate at day 42 was 45 % ( 95 % confidence interval [ CI ] , 36%-53 % ) for AAQ and 13 % ( 95 % CI , 7.2%-19 % ) for DHP ( hazard ratio [ HR ] , 4.3 ; 95 % CI , 2.5 - 7.2 ; P<.001 ) . Rates of both recrudescence of P. falciparum infection and recurrence of P. vivax infection were significantly higher after receipt of AAQ than after receipt of DHP ( HR , 3.4 [ 95 % CI , 1.2 - 9.4 ] and 4.3 [ 95 % CI , 2.2 - 8.2 ] , respectively ; P<.001 ) . By the end of the study , AAQ recipients were 2.95-fold ( 95 % CI , 1.2- to 4.9-fold ) more likely to be anemic and 14.5-fold ( 95 % CI , 3.4- to 61-fold ) more likely to have carried P. vivax gametocytes . CONCLUSIONS DHP was more effective and better tolerated than AAQ against multidrug-resistant P. falciparum and P. vivax infections . The prolonged therapeutic effect of piperaquine delayed the time to P. falciparum reinfection , decreased the rate of recurrence of P. vivax infection , and reduced the risk of P. vivax gametocyte carriage and anemia Background Many countries have implemented artemisinin-based combination therapy ( ACT ) for the first-line treatment of malaria . Although many studies have been performed on efficacy and tolerability of the combination arthemeter-lumefantrine ( AL ) or dihydroartemisinin-piperaquine ( DP ) , less is known of the effect of these drugs on gametocyte development , which is an important issue in malaria control . Methods and results In this two-arm r and omized controlled trial , 146 children were treated with either AL or DP . Both groups received directly observed therapy and were followed for 28 days after treatment . Blood sample s were analysed with microscopy and NASBA . In comparison with microscopy NASBA detected much more gametocyte positive individuals . Moreover , NASBA showed a significant difference in gametocyte clearance in favour of AL compared to DP . The decline of parasitaemia was slower and persistence or development of gametocytes was significantly higher and longer at day 3 , 7 and 14 in the DP group but after 28 days no difference could be observed between both treatment arms . Conclusion Although practical considerations could favour the use of one drug over another , the effect on gametocytogenesis should also be taken into account and studied further using molecular tools like NASBA . This also applies when a new drug is introduced . Trial registration Current controlled trials IS RCT Background Artemisinin combination therapy has become the st and ard of care for uncomplicated malaria in most of Africa . However , there is limited data on the safety and tolerability of these drugs , especially in young children and patients co-infected with HIV . Methods A longitudinal , r and omized controlled trial was conducted in a cohort of HIV-infected and uninfected children aged 4 - 22 months in Tororo , Ug and a. Participants were r and omized to treatment with artemether-lumefantrine ( AL ) or dihydroartemisinin-piperaquine ( DP ) upon diagnosis of their first episode of uncomplicated malaria and received the same regimen for all subsequent episodes . Participants were actively monitored for adverse events for 28 days and then passively for up to 63 days after treatment . This study was registered in Clinical Trials.gov ( registration # NCT00527800 ) . Results A total of 122 children were r and omized to AL and 124 to DP , result ing in 412 and 425 treatments , respectively . Most adverse events were rare , with only cough , diarrhoea , vomiting , and anaemia occurring in more than 1 % of treatments . There were no differences in the risk of these events between treatment groups . Younger age was associated with an increased risk of diarrhoea in both the AL and DP treatment arms . Retreatment for malaria within 17 - 28 days was associated with an increased risk of vomiting in the DP treatment arm ( HR = 6.47 , 95 % CI 2.31 - 18.1 , p < 0.001 ) . There was no increase in the risk of diarrhoea or vomiting for children who were HIV-infected or on concomitant therapy with antiretrovirals or trimethoprim-sulphamethoxazole prophylaxis . Conclusion Both AL and DP were safe and well tolerated for the treatment of uncomplicated malaria in young HIV-infected and uninfected children . Trial Registration Clinical Trials.gov : NCT00527800 ; http:// clinical Background The emergence of artemisinin-resistant P. falciparum malaria in South-East Asia highlights the need for continued global surveillance of the efficacy of artemisinin-based combination therapies . Methods On the Kenyan coast we studied the treatment responses in 474 children 6–59 months old with uncomplicated P. falciparum malaria in a r and omized controlled trial of dihydroartemisinin-piperaquine vs. artemether-lumefantrine from 2005 to 2008 . ( IS RCT N88705995 ) Results The proportion of patients with residual parasitemia on day 1 rose from 55 % in 2005–2006 to 87 % in 2007–2008 ( odds ratio , 5.4 , 95%CI , 2.7–11.1 ; P<0.001 ) and from 81 % to 95 % ( OR , 4.1 , 95%CI , 1.7–9.9 ; P = 0.002 ) in the DHA-PPQ and AM-LM groups , respectively . In parallel , Kaplan-Meier estimated risks of apparent recrudescent infection by day 84 increased from 7 % to 14 % ( P = 0.1 ) and from 6 % to 15 % ( P = 0.05 ) with DHA-PPQ and AM-LM , respectively . Coinciding with decreasing transmission in the study area , clinical tolerance to parasitemia ( defined as absence of fever ) declined between 2005–2006 and 2007–2008 ( OR body temperature > 37.5 ° C , 2.8 , 1.9–4.1 ; P<0.001 ) . Neither in vitro sensitivity of parasites to DHA nor levels of antibodies against parasite extract accounted for parasite clearance rates or changes thereof . Conclusions The significant , albeit small , decline through time of parasitological response rates to treatment with ACTs may be due to the emergence of parasites with reduced drug sensitivity , to the coincident reduction in population -level clinical immunity , or both . Maintaining the efficacy of artemisinin-based therapy in Africa would benefit from a better underst and ing of the mechanisms underlying reduced parasite clearance rates . Trial Registration Controlled-Trials.com IS RCT Background The choice of appropriate artemisinin-based combination therapy depends on several factors ( cost , efficacy , safety , reinfection rate and simplicity of administration ) . To assess whether the combination dihydroartemisinin-piperaquine ( DP ) could be an alternative to artemether-lumefantrine ( AL ) , the efficacy and the tolerability of the two products for the treatment of uncomplicated falciparum malaria in sub-Saharan Africa have been compared . Methods A multicentric open r and omized controlled clinical trial of three-day treatment of DP against AL for the treatment of two parallel groups of patients aged two years and above and suffering from uncomplicated falciparum malaria was carried out in Cameroon , Côte d'Ivoire and Senegal . Within each group , patients were r and omly assigned supervised treatment . DP was given once a day for three days and AL twice a day for three days . Follow-up visits were performed on day 1 to 4 and on day 7 , 14 , 21 , 28 to evaluate clinical and parasitological results . The primary endpoint was the recovery rate by day 28 . Results Of 384 patients enrolled , 197 were assigned DP and 187 AL . The recovery rates adjusted by genotyping , 99.5 % in the DP group and 98.9 % in the AL group , were not statistically different ( p = 0.538 ) . No Early Therapeutic Failure ( ETF ) was observed . At day 28 , two patients in the DP group and five in AL group had recurrent parasitaemia with Plasmodium falciparum . In the DP group , after PCR genotyping , one of the two recurrences was classified as a new infection and the other as recrudescence . In AL group , two recurrences were classified after correction by PCR as recrudescence . All cases of recrudescence were classified as Late Parasitological Failure ( LPF ) . In each group , a rapid recovery from fever and parasitaemia was noticed . More than 90 % of patients did no longer present fever or parasitaemia 48 hours after treatment . Both drugs were well tolerated . Indeed , no serious adverse events were reported during the follow-up period . Most of the adverse events which developed were moderate and did not result in the treatment being stopped in either treatment group . Conclusions Dihydroartemisinin-piperaquine was as effective and well-tolerated as artemether-lumefantrine in the treatment of uncomplicated falciparum malaria . In addition , dihydroartemisinin-piperaquine , a single daily dose , could be an advantage over artemether-lumefantrine in Africa because of better treatment observance Background A practical and simple regimen for all malaria species is needed towards malaria elimination in Indonesia . It is worth to compare the efficacy and safety of a single dose of artemisinin-naphthoquine ( AN ) with a three-day regimen of dihydroartemisinin-piperaquine ( DHP ) , the existing programme drug , in adults with uncomplicated symptomatic malaria . Methods This is a phase III , r and omized , open label using sealed envelopes , multi-centre , comparative study between a single dose of AN and a three-day dose of DHP in Jayapura and Maumere . The modified WHO inclusion and exclusion criteria for efficacy study were used in this trial . A total of 401 eligible adult malaria subjects were hospitalized for three days and r and omly treated with AN four tablets single dose on day 0 or DHP three to four tablets single daily dose for three days , and followed for 42 days for physical examination , thick and thin smears microscopy , and other necessary tests . The efficacy of drug was assessed by polymerase chain reaction ( PCR ) uncorrected and corrected . Results There were 153 Plasmodium falciparum , 158 Plasmodium vivax and 90 P. falciparum/P. vivax malaria . Mean of fever clearance times were similar , 13.0 ± 10.3 hours in AN and 11.3 ± 7.3 hours in DHP groups . The mean of parasite clearance times were longer in AN compared with DHP ( 28.0 ± 11.7 hours vs 25.5 ± 12.2 hours , p = 0.04 ) . There were only 12 PCR-corrected P. falciparum late treatment failures : seven in AN and five in DHP groups . The PCR uncorrected and corrected on day −42 of adequate clinical and parasitological responses for treatment of any malaria were 93.7 % ( 95 % Cl : 90.3–97.2 ) and 96.3 % ( 95 % Cl : 93.6–99.0 ) in AN , 96.3 % ( 95 % Cl : 93.5–99.0 ) and 97.3 % ( 95 % Cl : 95.0–99.6 ) in DHP groups . Few and mild adverse events were reported . All the abnormal haematology and blood chemistry values had no clinical abnormality . Conclusion AN and DHP are confirmed very effective , safe and tolerate for treatment of any malaria . Both drugs are promising for multiple first-line therapy policies in Indonesia ABSTRACT The population pharmacokinetics of piperaquine in adults and children with uncomplicated Plasmodium falciparum malaria treated with two different dosage regimens of dihydroartemisinin-piperaquine were characterized . Piperaquine pharmacokinetics in 98 Burmese and Karen patients aged 3 to 55 years were described by a two-compartment disposition model with first-order absorption and interindividual r and om variability on all parameters and were similar with the three- and four-dose regimens . Children had a lower body weight-normalized oral clearance than adults , result ing in longer terminal elimination half-lives and higher total exposure to piperaquine ( area under the concentration-time curve from 0 to 63 days [ AUCday 0 - 63 ] ) . However , children had lower plasma concentrations in the therapeutically relevant posttreatment prophylactic period ( AUCday 3 - 20 ) because of smaller body weight-normalized central volumes of distribution and shorter distribution half-lives . Our data lend further support to a simplified once-daily treatment regimen to improve treatment adherence and efficacy and indicate that weight-adjusted piperaquine doses in children may need to be higher than in adults We conducted an open , r and omized clinical trial of oral dihydroartemisinin-piperaquine ( DP ) versus artesunate-mefloquine ( AM ) in 300 patients in Laos with uncomplicated Plasmodium falciparum malaria as part of a multicentre study in Asia . Survival analysis and adjustment for re-infection showed that the 63-day cure rates ( 95 % confidence interval [ CI ] ) were 100 % for AM and 99.5 % ( 96.4–99.8 % ) for DP . The 63-day cure rates per protocol were 99 % ( 97 of 98 ) for AM and 99.5 % ( 196 of 197 ) for DP ( P = 0.55 ) . The difference ( AM minus DP ) in cure rates ( 95 % CI ) was −0.5 % ( −5.1 to 2.0 % ) , which is within the 5 % non-inferiority margin . The median fever and parasite clearance times were also similar for AM and DP . The proportion of patients with at least one recorded potential adverse event was significantly higher in the AM group ( 38 of 87 , 44 % ) than in the DP group ( 57 of 182 , 31 % ) ( relative risk = 0.6 , 95 % CI = 0.4–0.9 ; P = 0.04 ) . Dihydroartemisinin-piperaquine is not inferior to AM in the treatment of uncomplicated P. falciparum malaria in Laos and is associated with fewer adverse effects . The results of this study were similar to those of the larger multicentre study Background By 2009 , there were worrying signs from western Cambodia that parasitological responses to artesunate-containing treatment regimens for uncomplicated Plasmodium falciparum malaria were slower than elsewhere which suggested the emergence of artemisinin resistance . Vietnam shares a long l and border with Cambodia with a large number of migrants crossing it on a daily basis . Therefore , there is an urgent need to investigate whether there is any evidence of a change in the parasitological response to the artemisinin derivatives in Vietnam . Methods From August 2010 to May 2011 , a r and omized controlled clinical trial in uncomplicated falciparum malaria was conducted to compare two doses of artesunate ( AS ) ( 2mg/kg/day versus 4 mg/kg/day for three days ) followed by dihydroartemisinin-piperaquine ( DHA-PPQ ) and a control arm of DHA-PPQ . The goal was characterization of the current efficacy of artesunate in southern Vietnam . The primary endpoint of this study was the parasite clearance half-life ; secondary endpoints included the parasite reduction ratios at 24 and 48 hours and the parasite clearance time . Results 166 patients were recruited into the study . The median parasite clearance half-lives were 3.54 ( AS 2mg/kg ) , 2.72 ( AS 4mg/kg ) , and 2.98 hours ( DHA-PPQ ) ( p=0.19 ) . The median parasite-reduction ratio at 24 hours was 48 in the AS 2mg/kg group compared with 212 and 113 in the other two groups , respectively ( p=0.02 ) . The proportions of patients with a parasite clearance time of > 72 hours for AS 2mg/kg , AS 4mg/kg and DHA-PPQ were 27 % , 27 % , and 22 % , respectively . Early treatment failure occurred in two ( 4 % ) and late clinical failure occurred in one ( 2 % ) of the 55 patients in the AS 2mg/kg group , as compared with none in the other two study arms . The PCR-corrected adequate clinical and parasitological response ( APCR ) rates in the three groups were 94 % , 100 % , and 100 % ( p=0.04 ) . Conclusions This study demonstrated faster P. falciparum parasite clearance in southern Vietnam than in western Cambodia but slower clearance in comparison with historical data from Vietnam . Further studies to determine whether this represents the emergence of artemisinin resistance in this area are needed . Currently , the therapeutic response to DHA-PPQ remains satisfactory in southern Vietnam . Trial registration Background Artemisinin combination therapies ( ACTs ) are currently the preferred option for treating uncomplicated malaria . Dihydroartemisinin-piperaquine ( DHA-PQP ) is a promising fixed-dose ACT with limited information on its safety and efficacy in African children . Methodology /Principal Findings The non-inferiority of DHA-PQP versus artemether-lumefantrine ( AL ) in children 6–59 months old with uncomplicated P. falciparum malaria was tested in five African countries ( Burkina Faso , Kenya , Mozambique , Ug and a and Zambia ) . Patients were r and omised ( 2∶1 ) to receive either DHA-PQP or AL . Non-inferiority was assessed using a margin of −5 % for the lower limit of the one-sided 97.5 % confidence interval on the treatment difference ( DHA-PQP vs. AL ) of the day 28 polymerase chain reaction ( PCR ) corrected cure rate . Efficacy analysis was performed in several population s , and two of them are presented here : intention-to-treat ( ITT ) and enlarged per- protocol ( ePP ) . 1553 children were r and omised , 1039 receiving DHA-PQP and 514 AL . The PCR-corrected day 28 cure rate was 90.4 % ( ITT ) and 94.7 % ( ePP ) in the DHA-PQP group , and 90.0 % ( ITT ) and 95.3 % ( ePP ) in the AL group . The lower limits of the one-sided 97.5 % CI of the difference between the two treatments were −2.80 % and −2.96 % , in the ITT and ePP population s , respectively . In the ITT population , the Kaplan-Meier estimate of the proportion of new infections up to Day 42 was 13.55 % ( 95 % CI : 11.35%–15.76 % ) for DHA-PQP vs 24.00 % ( 95 % CI : 20.11%–27.88 % ) for AL ( p<0.0001 ) . Conclusions / Significance DHA-PQP is as efficacious as AL in treating uncomplicated malaria in African children from different endemicity setting s , and shows a comparable safety profile . The occurrence of new infections within the 42-day follow up was significantly lower in the DHA-PQP group , indicating a longer post-treatment prophylactic effect . Trial Registration Controlled-trials.com IS RCT BACKGROUND Artemisinin-based combinations are judged the best treatments for multidrug-resistant Plasmodium falciparum malaria . Artesunate-mefloquine is widely recommended in southeast Asia , but its high cost and tolerability profile remain obstacles to widespread deployment . To assess whether dihydroartemisinin-piperaquine is a suitable alternative to artesunate-mefloquine , we compared the safety , tolerability , efficacy , and effectiveness of the two regimens for the treatment of uncomplicated falciparum in western Myanmar ( Burma ) . METHODS We did an open r and omised comparison of 3-day regimens of artesunate-mefloquine ( 12/25 mg/kg ) versus dihydroartemisinin-piperaquine ( 6.3/50 mg/kg ) for the treatment of children aged 1 year or older and in adults with uncomplicated falciparum malaria in Rakhine State , western Myanmar . Within each group , patients were r and omly assigned supervised or non-supervised treatment . The primary endpoint was the PCR-confirmed parasitological failure rate by day 42 . Failure rates at day 42 were estimated by Kaplan-Meier survival analysis . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N27914471 . FINDINGS Of 652 patients enrolled , 327 were assigned dihydroartemisinin-piperaquine ( 156 supervised and 171 not supervised ) , and 325 artesunate-mefloquine ( 162 and 163 , respectively ) . 16 patients were lost to follow-up , and one patient died 22 days after receiving dihydroartemisinin-piperaquine . Recrudescent parasitaemias were confirmed in only two patients ; the day 42 failure rate was 0.6 % ( 95 % CI 0.2 - 2.5 ) for dihydroartemisinin-piperaquine and 0 ( 0 - 1.2 ) for artesunate-mefloquine . Whole-blood piperaquine concentrations at day 7 were similar for patients with observed and non-observed dihydroartemisinin-piperaquine treatment . Gametocytaemia developed more frequently in patients who had received dihydroartemisinin-piperaquine than in those on artesunate-mefloquine : day 7 , 18 ( 10 % ) of 188 versus five ( 2 % ) of 218 ; relative risk 4.2 ( 1.6 - 11.0 ) p=0.011 . INTERPRETATION Dihydroartemisinin-piperaquine is a highly efficacious and inexpensive treatment of multidrug-resistant falciparum malaria and is well tolerated by all age groups . The effectiveness of the unsupervised treatment , as in the usual context of use , equalled its supervised efficacy , indicating good adherence without supervision . Dihydroartemisinin-piperaquine is a good alternative to artesunate-mefloquine BACKGROUND Artemisinin-combination therapy ( ACT ) is recommended as first-line treatment of falciparum malaria throughout the world , and fixed-dose combinations are preferred by WHO ; whether a single gametocytocidal dose of primaquine should be added is unknown . We aim ed to compare effectiveness of four fixed-dose ACTs and a loose tablet combination of artesunate and mefloquine , and assess the addition of a single gametocytocidal dose of primaquine . METHODS In an open-label r and omised trial in clinics in Rakhine state , Kachin state , and Shan state in Myanmar ( Burma ) between Dec 30 , 2008 , and March 20 , 2009 , we compared the effectiveness of all four WHO-recommended fixed-dose ACTs ( artesunate-mefloquine , artesunate-amodiaquine , dihydroartemisinin-piperaquine , artemether-lumefantrine ) and loose artesunate-mefloquine in Burmese adults and children . Eligible patients were those who presented to the clinics with acute uncomplicated Plasmodium falciparum malaria or mixed infection , who were older than 6 months , and who weighed more than 5 kg . Treatments were r and omised in equal numbers within blocks of 50 and allocation was in sealed envelopes . All patients were also r and omly assigned to receive either a single dose of primaquine 0·75 mg base/kg or not . Patients were followed up for 63 days . Treatment groups were compared by analysis of variance and multiple logistic regression . The primary outcome was the 63 day recrudescence rate . This study is registered with clinical trials.gov , number NCT00902811 . FINDINGS 155 patients received artesunate-amodiaquine , 162 artemether-lumefantrine , 169 artesunate-mefloquine , 161 loose artesunate-mefloquine , and 161 dihydroartemisinin-piperaquine . By day 63 of follow-up , 14 patients ( 9·4 % ; 95 % CI 5·7 - 15·3 % ) on artesunate-amodiaquine had recrudescent P falciparum infections , a rate significantly higher than for artemether-lumefantrine ( two patients ; 1·4 % ; 0·3 - 5·3 ; p=0·0013 ) , fixed-dose artesunate-mefloquine ( 0 patients ; 0 - 2·3 ; p<0·0001 ) , loose artesunate-mefloquine ( two patients ; 1·3 % ; 0·3 - 5·3 ; p=0·0018 ) , and dihydroartemisinin-piperaquine ( two patients 1·3 % ; 0·3 - 5·2 % ; p=0·0012 ) . Hazard ratios for re-infection ( 95 % CI ) after artesunate-amodiaquine were 3·2 ( 1·3 - 8·0 ) compared with the two artesunate-mefloquine groups ( p=0·01 ) , 2·6 ( 1·0 - 6 - 0 ) compared with artemether-lumefantrine ( p=0·04 ) , and 2·3 ( 0·9 - 6·0 ) compared with dihydroartemisinin-piperaquine ( p=0·08 ) . Mixed falciparum and vivax infections were common : 129 ( 16 % ) had a mixed infection at presentation and 330 ( 41 % ) patients had one or more episodes of Plasmodium vivax infection during follow-up . The addition of a single dose of primaquine ( 0·75 mg/kg ) reduced P falciparum gametocyte carriage substantially : rate ratio 11·9 ( 95 % CI 7·4 - 20·5 ) . All regimens were well tolerated . Adverse events were reported by 599 patients , most commonly vomiting and dizziness . Other side-effects were less common and were not related to a specific treatment . INTERPRETATION Artesunate-amodiaquine should not be used in Myanmar , because the other ACTs are substantially more effective . Artesunate-mefloquine provided the greatest post-treatment suppression of malaria . Adding a single dose of primaquine would substantially reduce transmission potential . Vivax malaria , not recurrent falciparum malaria , is the main complication after treatment of P falciparum infections in this region . FUNDING Médecins sans Frontières ( Holl and ) and the Wellcome Trust Mahidol University Oxford Tropical Medicine Research Programme Background The treatment of falciparum malaria poses unique challenges in setting s where malaria transmission intensity is high because recurrent infections are common . These could be new infections , recrudescences , or a combination of the two . Though several African countries continue to use quinine as the second line treatment for patients with recurrent infections , there is little information on its efficacy when used for rescue therapy . Moreover , such practice goes against the World Health Organisation ( WHO ) recommendation to use combination therapy for uncomplicated malaria . Methods We conducted a nested , r and omized , open label , three-arm clinical trial of rescue therapy in children 6–59 months old with recurrent malaria infection during 28 days post treatment with artemisinin combination treatment ( ACT ) . Patients were r and omly assigned to receive either quinine , artemether-lumefantrine ( AL ) or dihydroartemisinin-piperaquine ( DHAPQ ) , and actively followed up for 28 days . Findings Among 220 patients enrolled , 217 ( 98.6 % ) were assigned an efficacy outcome and 218 ( 99.1 % ) were assessed for safety . The risk of recurrent infection was significantly higher in patients treated with quinine ( 70 % , 74/110 , HR = 3.9 ; 95 % CI : 2.4–6.7 , p<0.0001 ) and AL ( 60 % , 21/35 , HR = 3.3 ; 95 % CI : 1.8–6.3 , p<0.0002 ) , compared to DHAPQ ( 25 % , 18/72 ) . Recrudescence tended to be lower in the DHAPQ ( 1 % , 1/72 ) than in the quinine ( 7 % , 8/110 ) or AL ( 6 % , 2/35 ) group , though it was not statistically significant . No serious adverse events were reported . Conclusion Recurrent infections observed after the administration of an ACT can be successfully treated with an alternative ACT rather than with quinine . Trial Registration Current Controlled Trials IS RCT OBJECTIVE Artesunate-amodiaquine ( AAQ ) is efficacious for the treatment of uncomplicated Plasmodium falciparum malaria in Africa , but little is known about its efficacy in Southeast Asia . We compared the efficacy of dihydroartemisinin-piperaquine ( DHP ) and AAQ against falciparum malaria in central Vietnam . METHODS Open , r and omized clinical trial of 116 patients ( 36 children aged 6 - 14 years , 80 adults aged 15 - 60 years ) were r and omly allocated a 3-day course of either DHP ( approximately 2.3 mg/kg dihydroartemisinin plus approximately 18.5 mg/kg of piperaquine per day ) or AAQ ( approximately 4.4 mg/kg of artesunate plus approximately 10.6 mg/kg of amodiaquine per day ) . The follow-up period was 42 days . RESULTS The two drug combinations were well tolerated by all age groups with no obvious drug associated adverse events . Of the patients who completed 42 days of follow-up , 49 were on DHP ( 15 children , 34 adults ) and 49 were on AAQ ( 14 children , 35 adults ) . The 42 day cure rates adjusted for reinfection identified by PCR genotyping for the two groups were similar [ 100 % ( 49/49 ) and 98 % ( 48/49 ) for DHP and AAQ , respectively ] . With fewer reinfections , DHP appears to possess greater post-treatment prophylactic activity than AAQ . CONCLUSION AAQ , an inexpensive artemisinin-based combination , could be an additional option to DHP for the treatment of multidrug-resistant falciparum malaria in Vietnam Combination therapy that includes artemisinin derivatives cures most falciparum malaria infections . Lowering transmission by reducing gametocyte infectivity would be an additional benefit . To examine the effect of such therapy on transmission , Gambian children with Plasmodium falciparum malaria were treated with st and ard regimens of chloroquine or pyrimethamine-sulfadoxine alone or in combination with 1 or 3 doses of artesunate . The infectivity to mosquitoes of gametocytes in peripheral blood was determined 4 or 7 days after treatment . Infection of mosquitoes was observed in all treatment groups and was positively associated with gametocyte density . The probability of transmission was lowest in those who received pyrimethamine-sulfadoxine and 3 doses of artesunate , and it was 8-fold higher in the group that received pyrimethamine-sulfadoxine alone . Artesunate reduced posttreatment infectivity dramatically but did not abolish it completely . The study raises questions about any policy to use pyrimethamine-sulfadoxine alone as the first-line treatment for malaria Background Resistance in Plasmodium falciparum to commonly used anti-malarial drugs , especially chloroquine , is being increasingly documented in India . By 2007 , the first-line treatment for uncomplicated malaria has been revised to recommend artemisinin-based combination therapy ( ACT ) for all confirmed P. falciparum cases . Objective The objective of this study was to compare the efficacy , safety and tolerability between dihydroartemisinin-piperaquine ( DP ) and artesunate plus mefloquine ( A + M ) drug combinations in the treatment of uncomplicated P. falciparum malaria in India . Methods Between 2006 and 2007 , 150 patients with acute uncomplicated P. falciparum malaria were enrolled , r and omized to DP ( 101 ) or A + M ( 49 ) and followed up for 63 days as part of an open-label , non-inferiority , r and omized , phase III multicenter trial in Asia . Results The heterogeneity analysis showed no statistically significant difference between India and the other countries involved in the phase III study , for both the PCR-corrected and uncorrected cure rates . As shown at the whole study level , both forms of ACT were highly efficacious in India . In fact , in the per protocol population , the 63-day cure rates were 100 % for A + M and 98.8 % for DP . The DP combination exerted a significant post-treatment prophylactic effect , and compared with A + M a significant reduction in the incidence of new infections for DP was observed ( respectively 17.1 % versus 7.5 % of patients experienced new infection within follow up ) . Parasite and fever clearance was rapid in both treatment arms ( median time to parasite clearance of one day for both groups ) . Both DP and A + M were well tolerated , with the majority of adverse events of mild or moderate severity . The frequencies of individual adverse events were generally similar between treatments , although the incidence of post treatment adverse events was slightly higher in patients who received A + M with respect to those treated with DP . Conclusion DP is a new ACT displaying high efficacy and safety in the treatment of uncomplicated P. falciparum malaria and could potentially be considered for the first-line treatment of uncomplicated falciparum malaria in India . Trial registration Current Controlled Trials IS RCT N Objectives : To compare the efficacy and safety of artemether-lumefantrine ( AL ) and dihydroartemisinin-piperaquine ( DP ) for treating uncomplicated falciparum malaria in Ug and a. Design : R and omized single-blinded clinical trial . Setting : Apac , Ug and a , an area of very high malaria transmission intensity . Participants : Children aged 6 mo to 10 y with uncomplicated falciparum malaria . Intervention : Treatment of malaria with AL or DP , each following st and ard 3-d dosing regimens . Outcome measures : Risks of recurrent parasitemia at 28 and 42 d , unadjusted and adjusted by genotyping to distinguish recrudescences and new infections . Results : Of 421 enrolled participants , 417 ( 99 % ) completed follow-up . The unadjusted risk of recurrent falciparum parasitemia was significantly lower for participants treated with DP than for those treated with AL after 28 d ( 11 % versus 29 % ; risk difference [ RD ] 18 % , 95 % confidence interval [ CI ] 11%–26 % ) and 42 d ( 43 % versus 53 % ; RD 9.6 % , 95 % CI 0%–19 % ) of follow-up . Similarly , the risk of recurrent parasitemia due to possible recrudescence ( adjusted by genotyping ) was significantly lower for participants treated with DP than for those treated with AL after 28 d ( 1.9 % versus 8.9 % ; RD 7.0 % , 95 % CI 2.5%–12 % ) and 42 d ( 6.9 % versus 16 % ; RD 9.5 % , 95 % CI 2.8%–16 % ) . Patients treated with DP had a lower risk of recurrent parasitemia due to non-falciparum species , development of gametocytemia , and higher mean increase in hemoglobin compared to patients treated with AL . Both drugs were well tolerated ; serious adverse events were uncommon and unrelated to study drugs . Conclusion : DP was superior to AL for reducing the risk of recurrent parasitemia and gametocytemia , and provided improved hemoglobin recovery . DP thus appears to be a good alternative to AL as first-line treatment of uncomplicated malaria in Ug and a. To maximize the benefit of artemisinin-based combination therapy in Africa , treatment should be integrated with aggressive strategies to reduce malaria transmission intensity Background Malaria in Zambia remains a public health and developmental challenge , affecting mostly children under five and pregnant women . In 2002 , the first-line treatment for uncomplicated malaria was changed to artemether-lumefantrine ( AL ) that has proved to be highly efficacious against multidrug resistant Plasmodium falciparum . Objective The study objective was to determine whether dihydroartemisinin-piperaquine ( DHA/PQP ) had similar efficacy , safety and tolerability as AL for the treatment of children with uncomplicated P. falciparum malaria in Ndola , Zambia . Methods Between 2005 and 2006 , 304 children ( 6 - 59 months old ) with uncomplicated P. falciparum were enrolled , r and omized to AL ( 101 ) or DHA/PQP ( 203 ) and followed up for 42 days . Outcome of treatment was defined according to the st and ard WHO classification , i.e. early treatment failure ( ETF ) , late clinical failure ( LCF , late parasitological failure ( LPF ) and adequate clinical and parasitological response ( ACPR ) . Recurrent infections were genotyped to distinguish between recrudescence and new infection . Results No ETF was observed . At day 28 , PCR-uncorrected ACPR was 92 % in the DHA/PQP and 74 % in the AL arm ( OR : 4.05 ; 95%CI : 1.89 - 8.74 ; p < 0.001 ) . Most failure were new infections and PCR-corrected ACPR was similar in the two study arms ( OR : 0.69 ; 95%CI : 0.22 - 2.26 ; p = 0.33 ) . Similar results were observed for day 42 , i.e. higher PCR-uncorrected ACPR for DHA/PQP , mainly due to the difference observed up to day 28 , while the PCR-corrected ACPR was similar : DHA/PQP : 93 % ( 179/192 ) , AL : 93 % ( 84/90 ) , ( OR : 0.92 ; 95%CI : 0.30 - 2.64 ; p = 0.85 ) . Except for cough , more frequent in the DHA/PQP arm ( p = 0.04 ) , there were no differences between treatment arms in the occurrence of adverse events . Two serious adverse events were probably associated to AL treatment . Conclusion DHA/PQP was as efficacious , safe and well tolerated in treatment of uncomplicated malaria as AL , though in the latter group more new infections during the follow up were observed . DHA/PQP seems a potential c and i date to be used as an alternative first-line or rescue treatment in Zambia . Trial Registration IS RCT N16263443 , at http://www.controlled-trials.com/is rct Background Molecular genotyping is performed in anti-malarial trials to determine whether recurrent parasitaemia after therapy represents a recrudescence ( treatment failure ) or new infection . The use of capillary instead of agarose gel electrophoresis for genotyping offers technical advantages , but it is unclear whether capillary electrophoresis will result in improved classification of anti-malarial treatment outcomes . Methods Sample s were genotyped using both gel and capillary electrophoresis from r and omized trials of artemether-lumefantrine ( AL ) vs. dihydroartemisinin-piperaquine ( DP ) performed in two areas of Ug and a : Kanungu , where transmission is moderate , and Apac , where transmission is very high . Both gel and capillary methods evaluated polymorphic regions of the merozoite surface protein 1 and 2 and glutamine rich protein genes . Results Capillary electrophoresis detected more alleles and provided higher discriminatory power than agarose gel electrophoresis at both study sites . There was only moderate agreement between classification of outcomes with the two methods in Kanungu ( kappa = 0.66 ) and poor agreement in Apac ( kappa = 0.24 ) . Overall efficacy results were similar when using gel vs. capillary methods in Kanungu ( 42-day risk of treatment failure for AL : 6.9 % vs. 5.5 % , p = 0.4 ; DP 2.4 % vs. 2.9 % , p = 0.5 ) . However , the measured risk of recrudescence was significantly higher when using gel vs. capillary electrophoresis in Apac ( risk of treatment failure for AL : 17.0 % vs. 10.7 % , p = 0.02 ; DP : 8.5 % vs. 3.4 % , p = 0.03 ) . Risk differences between AL and DP were not significantly different whether gel or capillary methods were used . Conclusions Genotyping with gel electrophoresis overestimates the risk of recrudescence in anti-malarial trials performed in areas of high transmission intensity . Capillary electrophoresis provides more accurate outcomes for such trials and should be performed when possible . In areas of moderate transmission , gel electrophoresis appears adequate to estimate comparative risks of treatment failure Background Multi-drug resistant falciparum malaria is an important health problem in the Peruvian Amazon region . We carried out a r and omised open label clinical trial comparing mefloquine-artesunate , the current first line treatment in this region , with dihydroartemisinin-piperaquine . Methods and Findings Between July 2003 and July 2005 , 522 patients with P. falciparum uncomplicated malaria were recruited , r and omized ( 260 with mefloquine-artesunate and 262 with dihydroartemisinin-piperaquine ) , treated and followed up for 63 days . PCR-adjusted adequate clinical and parasitological response , estimated by Kaplan Meier survival and Per Protocol analysis , was extremely high for both drugs ( 99.6 % for mefloquine-artesunate and 98.4 % and for dihydroartemisinin-piperaquine ) ( RR : 0.99 , 95%CI [ 0.97−1.01 ] , Fisher Exact p = 0.21 ) . All recrudescences were late parasitological failures . Overall , gametocytes were cleared faster in the mefloquine-artesunate group ( 28 vs 35 days ) and new gametocytes tended to appear more frequently in patients treated with dihydroartemisinin-piperaquine ( day 7 : 8 ( 3.6 % ) vs 2 ( 0.9 % ) , RR : 3.84 , 95%CI [ 0.82–17.87 ] ) . Adverse events such as anxiety and insomnia were significantly more frequent in the mefloquine-artesunate group , both in adults and children . Conclusion Dihydroartemisinin-piperaquine is as effective as mefloquine-artesunate in treating uncomplicated P. falciparum malaria but it is better tolerated and more affordable than mefloquine-artesunate ( US$ 1.0 versus US$ 18.65 on the local market ) . Therefore , it should be considered as a potential c and i date for the first line treatment of P.falciparum malaria in Peru . Trial Registration Clinical Trials.gov BACKGROUND Artemisinin-based combination therapy ( ACT ) reduces the potential for malaria transmission , compared with non-ACTs . It is unclear whether this effect differs between ACTs . METHODS A total of 298 children ( age , 6 months to 10 years ) with uncomplicated falciparum malaria were r and omized to artemether-lumefantrine ( AL ; n = 153 ) or dihydroartemisinin-piperaquine ( DP ; n = 145 ) in Mbita , a community in western Kenya . Gametocyte carriage was determined by molecular methods on days 0 , 1 , 2 , 3 , 7 , 14 , 28 , and 42 after treatment initiation . The gametocyte infectiousness to mosquitoes was determined by mosquito-feeding assays on day 7 after beginning therapy . RESULTS The cumulative risk of recurrent parasitemia on day 42 after initiation of treatment , unadjusted by polymerase chain reaction findings , was 20.7 % ( 95 % confidence interval [ CI ] , 14.4 - 28.2 ) for AL , compared with 3.7 % ( 95 % CI , 1.2 - 8.5 ) for DP ( P < .001 ) . The mean duration of gametocyte carriage was 5.5 days ( 95 % CI , 3.6 - 8.5 ) for AL and 15.3 days ( 95 % CI , 9.7 - 24.2 ) for DP ( P = .001 ) . The proportion of mosquitoes that became infected after feeding on blood from AL-treated children was 1.88 % ( 43 of 2293 ) , compared with 3.50 % ( 83 of 2371 ) for those that fed on blood from DP-treated children ( P = .06 ) ; the oocyst burden among mosquitoes was lower among those that fed on blood from AL-treated children ( P = .005 ) CONCLUSIONS : While DP was associated with a longer prophylactic time after treatment , gametocyte carriage and malaria transmission to mosquitoes was lower after AL treatment . CLINICAL TRIALS REGISTRATION NCT00868465 BACKGROUND Artemisinin-based combination therapy is very effective in clearing asexual stages of malaria and reduces gametocytemia , but may not affect mature gametocytes . Primaquine is the only commercially available drug that eliminates mature gametocytes . METHODS We conducted a 2-arm , open-label , r and omized , controlled trial to evaluate the efficacy of single-dose primaquine ( 0.75 mg/kg ) following treatment with dihydroartemisinin-piperaquine ( DHP ) on Plasmodium falciparum gametocytemia , in Indonesia . Patients aged ≥5 years with uncomplicated falciparum malaria , normal glucose-6-phosphate dehydrogenase enzyme levels , and hemoglobin levels ≥8 g/dL were assigned by computerized-generating sequence to a st and ard 3-day course of DHP alone ( n = 178 ) or DHP combined with a single dose of primaquine on day 3 ( n = 171 ) . Patients were seen on days 1 , 2 , 3 , and 7 and then weekly for 42 days to assess the presence of gametocytes and asexual parasites by microscopy . Survival analysis was stratified by the presence of gametocytes on day 3 . RESULTS DHP prevented development of gametocytes in 277 patients without gametocytes on day 3 . In the gametocytemic patients ( n = 72 ) , primaquine was associated with faster gametocyte clearance ( hazard ratio = 2.42 [ 95 % confidence interval , 1.39 - 4.19 ] , P = .002 ) and reduced gametocyte densities ( P = .018 ) . The day 42 cure rate of asexual stages in the DHP + primaquine and DHP-only arms were : polymerase chain reaction ( PCR ) unadjusted , 98.7 % vs 99.4 % , respectively ; PCR adjusted , 100 % for both . Primaquine was well tolerated . CONCLUSIONS Addition of single-dose 0.75 mg/kg primaquine shortens the infectivity period of DHP-treated patients and should be considered in low-transmission regions that aim to control and ultimately eliminate falciparum malaria . Clinical Trials Registration . NCT01392014 Background Ug and a recently adopted artemether-lumefantrine ( AL ) as the recommended first-line treatment for uncomplicated malaria . However , AL has several limitations , including a twice-daily dosing regimen , recommendation for administration with fatty food , and a high risk of reinfection soon after therapy in high transmission areas . Dihydroartemisinin-piperaquine ( DP ) is a new alternative artemisinin-based combination therapy that is dosed once daily and has a long post-treatment prophylactic effect . We compared the efficacy and safety of AL with DP in Kanungu , an area of moderate malaria transmission . Methodology /Principal Findings Patients aged 6 months to 10 years with uncomplicated falciparum malaria were r and omized to therapy and followed for 42 days . Genotyping was used to distinguish recrudescence from new infection . Of 414 patients enrolled , 408 completed follow-up . Compared to patients treated with artemether-lumefantrine , patients treated with dihydroartemisinin-piperaquine had a significantly lower risk of recurrent parasitaemia ( 33.2 % vs. 12.2 % ; risk difference = 20.9 % , 95 % CI 13.0–28.8 % ) but no statistically significant difference in the risk of treatment failure due to recrudescence ( 5.8 % vs. 2.0 % ; risk difference = 3.8 % , 95 % CI −0.2–7.8 % ) . Patients treated with dihydroartemisinin-piperaquine also had a lower risk of developing gametocytaemia after therapy ( 4.2 % vs. 10.6 % , p = 0.01 ) . Both drugs were safe and well tolerated . Conclusions / Significance DP is highly efficacious , and operationally preferable to AL because of a less intensive dosing schedule and requirements . Dihydroartemisinin-piperaquine should be considered for a role in the antimalarial treatment policy of Ug and a. Trial Registration Controlled-Trials.com IS RCT BACKGROUND Dihydroartemisinin-piperaquine ( DP ) is a new and relatively inexpensive artemisinin-containing fixed-combination antimalarial treatment . An adult treatment course contained 6.4 mg/kg dihydroartemisinin ( DHA ) , which is > 40 % lower than the level in most artemisinin-containing combinations . This raised the possibility that the efficacy of the current coformulation may not be optimal in the treatment of multidrug-resistant falciparum malaria . METHODS In 2 large r and omized , controlled studies in Thail and , the recommended dose of DP was compared with a regimen with additional artemisinin derivative ( 12 mg/kg ; DP+ ) and with mefloquine plus artesunate ( MAS3 ) . RESULTS A total of 731 patients were included : 201 in a hospital-based study and 530 in a community study . Day-28 cure rates in the hospital-based study were 100 % ( 95 % confidence interval [ CI ] , 93.9%-100 % ) in the MAS3 and DP+ groups and 98.3 % ( 95 % CI , 91%-99.7 % ) in the DP group , with a single recrudescence on day 21 . In the community study , polymerase chain reaction genotyping-adjusted cure rates on day 63 were 96.1 % ( 95 % CI , 92.6%-99.7 % ) in the DP group , 98.3 % ( 95 % CI , 96.1%-100 % ) in the DP+ group , and 94.9 % ( 95 % CI , 91.2%-98.6 % ) in the MAS3 group ( P=.2 ) . Adverse events were few , with an excess of mild abdominal pain in the DP group . CONCLUSIONS The current dosage of DP ( 6.4 mg/kg DHA and 51.2 mg/kg piperaquine phosphate ) given over the course of 48 h is highly effective , safe , and well tolerated for the treatment of multidrug-resistant falciparum malaria , and its efficacy is not improved by the addition of more DHA To determine the optimum dose of artemisinin-piperaquine combination therapies for acute uncomplicated Plasmodium falciparum malaria , we examined 7 c and i date regimens in 411 patients admitted to the Bangkok Hospital for Tropical Diseases . The studies were performed from May 2005 to October 2005 and November 2005 to June 2006 . We compared 3-day courses of artesunate-mefloquine , artemether-lumefantrine ( Coartem ) and of dihydroartemisinin-piperaquine ( Artekin ) as reference antimalarial treatments , with c and i date regimens using 2 - 3 day courses of artemisinin-piperaquine , Artequick . Initially , patients receiving each of the regimens had a rapid clinical and parasitological response . All treatments were well tolerated and no serious adverse effects occurred . The 28-day cure rates were < 80 % for the 2-day treatments with artemisinin-piperaquine at 2.4 mg/kg and 14.4 mg/kg , respectively , in the first study period and artemisinin-piperaquine at 3.2 mg/kg and 16.0 mg/kg , respectively , but > 98 % for the 3-day regimens . These results suggest that a 3-day course of artemisinin-piperaquine at 3.2 mg/kg and 16.0 mg/kg , respectively , deserve further evaluation as an alternative treatment for multidrug-resistant P. falciparum malaria BACKGROUND The burden of Plasmodium vivax infections has been underappreciated , especially in southeast Asia where chloroquine resistant strains have emerged . Our aim was to compare the safety and efficacy of dihydroartemisinin-piperaquine with that of artemether-lumefantrine in patients with uncomplicated malaria caused by multidrug-resistant P falciparum and P vivax . METHODS 774 patients in southern Papua , Indonesia , with slide-confirmed malaria were r and omly assigned to receive either artemether-lumefantrine or dihydroartemisinin-piperaquine and followed up for at least 42 days . The primary endpoint was the overall cumulative risk of parasitological failure at day 42 with a modified intention-to-treat analysis . This trial is registered with Clinical Trials.gov , trial number 00157833 . FINDINGS Of the 754 evaluable patients enrolled , 466 had infections with P falciparum , 175 with P vivax , and 113 with a mixture of both species . The overall risk of failure at day 42 was 43 % ( 95 % CI 38 - 48 ) for artemether-lumefantrine and 19 % ( 14 - 23 ) for dihydroartemisinin-piperaquine ( hazard ratio=3.0 , 95 % CI 2.2 - 4.1 , p<0.0001 ) . After correcting for reinfections , the risk of recrudescence of P falciparum was 4.4 % ( 2.6 - 6.2 ) with no difference between regimens . Recurrence of vivax occurred in 38 % ( 33 - 44 ) of patients given artemether-lumefantrine compared with 10 % ( 6.9 - 14.0 ) given dihydroartemisinin-piperaquine ( p<0.0001 ) . At the end of the study , patients receiving dihydroartemisinin-piperaquine were 2.0 times ( 1.2 - 3.6 ) less likely to be anaemic and 6.6 times ( 2.8 - 16 ) less likely to carry vivax gametocytes than were those given artemether-lumefantrine . INTERPRETATION Both dihydroartemisinin-piperaquine and artemether-lumefantrine were safe and effective for the treatment of multidrug-resistant uncomplicated malaria . However , dihydroartemisinin-piperaquine provided greater post-treatment prophylaxis than did artemether-lumefantrine , reducing P falciparum reinfections and P vivax recurrences , the clinical public-health importance of which should not be ignored ABSTRACT The relationship between malnutrition and malaria in young children is under debate , and no studies evaluating the association between malnutrition and response to artemisinin-based combination therapies ( ACTs ) have been published . We evaluated the association between malnutrition and response to antimalarial therapy in Ug and an children treated with ACTs for repeated episodes of malaria . Children aged 4 to 12 months diagnosed with uncomplicated malaria were r and omized to dihydroartemisinin-piperaquine ( DP ) or artemether-lumefantrine ( AL ) and followed for up to 2 years . All HIV-exposed and HIV-infected children received trimethoprim-sulfamethoxazole prophylaxis ( TS ) . The primary exposure variables included height-for-age and weight-for-age z scores . Outcomes included parasite clearance at days 2 and 3 and risk of recurrent parasitemia after 42 days of follow-up . Two hundred ninety-two children were r and omized to DP or AL , result ing in 2,013 malaria treatments . Fewer than 1 % of patients had a positive blood smear by day 3 ( DP , 0.2 % ; AL , 0.6 % [ P = 0.18 ] ) . There was no significant association between height-for-age or weight-for-age z scores and a positive blood smear 2 days following treatment . For children treated with DP but not on TS , decreasing height-for-age z scores of < −1 were associated with a higher risk of recurrent parasitemia than a height-for-age z score of > 0 ( hazard ratio [ HR ] for height-for-age z score of < −1 and ≥−2 = 2.89 [ P = 0.039 ] ; HR for height-for-age z score of < −2 = 3.18 [ P = 0.022 ] ) . DP and AL are effective antimalarial therapies in chronically malnourished children in a high-transmission setting . However , children with mild to moderate chronic malnutrition not taking TS are at higher risk for recurrent parasitemia and may be considered a target for chemoprevention OBJECTIVES To compare the efficacy and tolerability of dihydroartemisinin-piperaquine ( DHA-PQP ) with that of a 3-day regimen of mefloquine and artesunate ( MAS3 ) for the treatment of uncomplicated falciparum malaria in Cambodia . METHOD R and omized open-label non-inferiority study over 64 days . RESULTS Four hundred and sixty-four patients were included in the study . The polymerase chain reaction genotyping-adjusted cure rates on day 63 were 97.5 % ( 95 % confidence interval , CI , 93.8 - 99.3 ) for DHA-PQP and 97.5 % ( 95 % CI , 93.8 - 99.3 ) for MAS3 , P = 1 . There were no serious adverse events , but significantly more episodes of vomiting ( P = 0.03 ) , dizziness ( P = 0.002 ) , palpitations ( P = 0.04 ) , and sleep disorders ( P = 0.03 ) reported in the MAS3 treatment group , consistent with the side-effect profile of mefloquine . CONCLUSIONS DHA-PQP was as efficacious as MAS3 , but much better tolerated , making it more appropriate for use in a routine programme setting . This highly efficacious , safe and more affordable fixed-dose combination could become the treatment of choice for Plasmodium falciparum malaria in Cambodia AIMS To assess the haemodynamic , electrocardiographic and glycaemic effects of piperaquine-dihydroartemisinin ( Artekin ) fixed combination therapy in uncomplicated malaria . METHODS Sixty-two Cambodians ( 32 children and 30 adults ) with falciparum or vivax malaria were given Artekin given as four age-based oral doses over 32 h. Supine and erect blood pressure , the electrocardiographic QT interval and plasma glucose were measured before treatment and then at regular intervals during a 4-day admission period as part of efficacy and safety monitoring . QT intervals were rate-corrected ( QTc ) using Bazett 's formula . RESULTS Artekin therapy was well tolerated and all patients responded to treatment . Average parasite and fever clearance times were 19 and 12 h , respectively . The pretreatment mean fall in systolic blood pressure on st and ing was 8 + /- 6 mmHg and 6-hourly measurements over 72 h showed no significant change ( P = 0.48 ) . There was a significant lengthening of the mean QTc to a maximum of 11 ms(0.5 ) ( 95 % confidence interval 4 - 18 ms(0.5 ) ) relative to baseline at 24 h ( P = 0.003 ) . The maximal QTc prolongation observed in any patient was 53 ms(0.5 ) . There was a mean 0.4 mmol l(-1 ) reduction in the post-absorptive plasma glucose during the first 48 h but no episodes of hypoglycaemia ( plasma glucose < 3.0 mmol l(-1 ) ) were observed at any time . CONCLUSIONS Artekin is safe and effective combination therapy for uncomplicated malaria in children and adults . Although piperaquine is a long half-life drug related to other quinoline compounds including chloroquine and quinine , no clinical ly significant cardiovascular or metabolic effects were observed OBJECTIVE To assess the therapeutic efficacy of the combinations dihydroartemisinin-piperaquine and artemether-lumefantrine in treating uncomplicated falciparum malaria cases in an area with high level resistance of Plasmodium falciparum to chloroquine in Hainan Province . METHODS Patients aged 1 to 60 with uncomplicated P. falciparum infection and parasite density 1,000 to 200,000 parasites/microl were enrolled following an informed consent . Eligible patients were r and omly assigned to 2 groups for receiving either a 3-day course of dihydroartemisinin-piperaquine ( 40/320 mg , DP , group A ) or 6-dose course of artemether/lumefantrine ( 20/120 mg tablets , AL , group B ) over three days . They were followed up with clinical and laboratory examinations until day 28 using st and ard WHO in vivo antimalarial drug test protocol . RESULTS Altogether 107 eligible patients were enrolled but 106 completed the study . Adequate clinical and parasitological response ( ACPR ) was observed in 51 ( 100 % ) and 55 ( 100 % ) cases in groups A and B respectively . The mean time of fever clearance and mean time of asexual parasite clearance were ( 20.99 + /- 11.38 ) h and ( 36.45 + /- 12.60 ) h in AL and ( 22.35 + /- 13.26)h and ( 34.99 + /- 12.28 ) h in DP , respectively . There was no statistical difference on the mean time of fever clearance and asexual parasite clearance between AL and DP ( P > 0.05 ) . None of the participants showed recrudescence and serious adverse effect . CONCLUSION Both combinations artemether-lumefantrine and dihydroartemisinin-piperaquine show a high cure rate and proper tolerability among the patients with uncomplicated falciparum malaria in Hainan Background The artemisinin-based combination treatment ( ACT ) of dihydroartemisinin ( DHA ) and piperaquine ( PQP ) is a promising novel anti-malarial drug effective against multi-drug resistant falciparum malaria . The aim of this study was to show non-inferiority of DHA/PQP vs. artesunate-mefloquine ( AS+MQ ) in Asia . Methods and Findings This was an open-label , r and omised , non-inferiority , 63-day follow-up study conducted in Thail and , Laos and India . Patients aged 3 months to 65 years with Plasmodium falciparum mono-infection or mixed infection were r and omised with an allocation ratio of 2∶1 to a fixed-dose DHA/PQP combination tablet ( adults : 40 mg/160 mg ; children : 20 mg/320 mg ; n = 769 ) or loose combination of AS+MQ ( AS : 50 mg , MQ : 250 mg ; n = 381 ) . The cumulative doses of study treatment over the 3 days were of about 6.75 mg/kg of DHA and 54 mg/kg of PQP and about 12 mg/kg of AS and 25 mg/kg of MQ . Doses were rounded up to the nearest half tablet . The primary endpoint was day-63 polymerase chain reaction ( PCR ) genotype-corrected cure rate . Results were 87.9 % for DHA/PQP and 86.6 % for AS+MQ in the intention-to-treat ( ITT ; 97.5 % one-sided confidence interval , CI : > −2.87 % ) , and 98.7 % and 97.0 % , respectively , in the per protocol population ( 97.5 % CI : > −0.39 % ) . No country effect was observed . Kaplan-Meier estimates of proportions of patients with new infections on day 63 ( secondary endpoint ) were significantly lower for DHA/PQP than AS+MQ : 22.7 % versus 30.3 % ( p = 0.0042 ; ITT ) . Overall gametocyte prevalence ( days 7 to 63 ; secondary endpoint ) , measured as person-gametocyte-weeks , was significantly higher for DHA/PQP than AS+MQ ( 10.15 % versus 4.88 % ; p = 0.003 ; ITT ) . Fifteen serious adverse events were reported , 12 ( 1.6 % ) in DHA/PQP and three ( 0.8 % ) in AS+MQ , among which six ( 0.8 % ) were considered related to DHA/PQP and three ( 0.8 % ) to AS+MQ . Conclusions DHA/PQP was a highly efficacious drug for P. falciparum malaria in areas where multidrug parasites are prevalent . The DHA/PQP combination can play an important role in the first-line treatment of uncomplicated falciparum malaria . Trial Registration Controlled-Trials.com IS RCT BACKGROUND Dihydroartemisinin-piperaquine ( DP ) is a fixed-combination antimalarial drug increasingly deployed in Southeast Asia . The current regimen involves 4 doses given over 3 days . Simplification of the dose regimen should facilitate treatment adherence and thereby increase effectiveness . METHODS In a r and omized , controlled , 3-arm trial conducted along the northwestern border of Thail and , the st and ard 4-dose course of DP ( DP4 ) was compared to an equivalent dose given as a once-daily regimen ( DP3 ) and to the st and ard treatment of mefloquine-artesunate ( MAS3 ) . RESULTS A total of 499 patients were included in the study . Times to fever and parasite clearance were similar in all groups . The PCR genotyping-adjusted cure rates at day 63 after treatment initiation were 95.7 % ( 95 % confidence interval [ 95 % CI ] , 92.2%-98.9 % ) for MAS3 , 100 % for DP4 , and 99.4 % ( 95 % CI , 98.1%-100 % ) for DP3 . The DP4 and DP3 cure rates were significantly higher than that for MAS3 ( P=.008 and P=.03 , respectively ) . All regimens were well tolerated . There were 3 deaths ( 1 in the MAS3 group and 2 in the DP3 group ) , all of which were considered to be unrelated to treatment . Rates of other adverse events were comparable between the groups , except for diarrhea , which was more common in the DP4 group ( P=.05 vs. the MAS3 group ) . CONCLUSIONS A once-daily , 3-dose regimen of DP is a highly efficacious treatment for multidrug-resistant falciparum malaria . This simple , safe , and relatively inexpensive fixed combination could become the treatment of choice for falciparum malaria BACKGROUND Malaria control is difficult where there is intense year-round transmission of multiple plasmodium species , such as in Papua New Guinea . METHODS Between April 2005 and July 2007 , we conducted an open-label , r and omized , parallel-group study of conventional chloroquine-sulfadoxine-pyrimethamine and artesunate-sulfadoxine-pyrimethamine , dihydroartemisinin-piperaquine , and artemether-lumefantrine in children in Papua New Guinea 0.5 to 5 years of age who had falciparum or vivax malaria . The primary end point was the rate of adequate clinical and parasitologic response at day 42 after the start of treatment with regard to Plasmodium falciparum , after correction for reinfections identified through polymerase-chain-reaction ( PCR ) genotyping of polymorphic loci in parasite DNA . Secondary end points included the rate of adequate clinical and parasitologic response at day 42 with regard to P. vivax without correction through PCR genotyping . RESULTS Of 2802 febrile children screened , 482 with falciparum malaria and 195 with vivax malaria were included . The highest rate of adequate clinical and parasitologic response for P. falciparum was in the artemether-lumefantrine group ( 95.2 % ) , as compared with 81.5 % in the chloroquine-sulfadoxine-pyrimethamine group ( P=0.003 ) , 85.4 % in the artesunate-sulfadoxine-pyrimethamine group ( P=0.02 ) , and 88.0 % in the dihydroartemisinin-piperaquine group ( P=0.06 ) . The rate of adequate clinical and parasitologic response for P. vivax in the dihydroartemisinin-piperaquine group ( 69.4 % ) was more than twice that in each of the other three treatment groups . The in vitro chloroquine and piperaquine levels that inhibited growth of local P. falciparum isolates by 50 % correlated significantly ( P<0.001 ) . Rash occurred more often with artesunate-sulfadoxine-pyrimethamine and dihydroartemisinin-piperaquine than with chloroquine-sulfadoxine-pyrimethamine ( P=0.004 for both comparisons ) . CONCLUSIONS The most effective regimens were artemether-lumefantrine against P. falciparum and dihydroartemisinin-piperaquine against P. vivax . The relatively high rate of treatment failure with dihydroartemisinin-piperaquine against P. falciparum may reflect cross-resistance between chloroquine and piperaquine . ( Australian New Zeal and Clinical Trials Registry number , ACTRN12605000550606 . BACKGROUND On the western border of Thail and the efficacy of mefloquine in the treatment of falciparum malaria has declined while gametocyte carriage rates have increased , which suggests increased transmissibility of these resistant infections . We compared the following antimalarial drugs in relation to subsequent Plasmodium falciparum gametocyte carriage : mefloquine , halofantrine , quinine , and the artemisinin derivatives . METHODS Between 1990 and 1995 we assessed gametocytaemia in a series of prospect i ve studies of antimalarial drug treatment in 5193 adults and children with acute uncomplicated falciparum malaria in an area of malarious hill forest on the western border of Thail and . Weekly parasite counts from thick and thin blood films were done during the 4-week ( 1990 - 93 ) or 9-week ( 1993 - 95 ) follow-up period . Gametocyte positivity rates and person gametocyte week ( PGW ) rates were calculated to measure gametocyte carriage and transmission potential . FINDINGS In primary P falciparum infections the gametocyte carriage rate was significantly higher after treatment with mefloquine than after treatment with the artemisinin derivatives ( PGW 34.1 [ 95 % CI 25.2 - 42.9 ] vs 3.9 [ 1.9 - 5.9 ] per 1000 person weeks ; relative risk 8.0 [ 4.1 - 15.6 ] ; p<0.0001 ) . Recrudescent infections were associated with increased gametocyte carrier rates ( relative risk 2.2 [ 1.6 - 3.0 ] ; p<0.0001 ) , but retreatment with artemisinin derivatives reduced subsequent gametocyte carriage 18.5 fold [ 3.5 - 98 ] compared with mefloquine retreatment and 6.8 fold ( 3.1 - 15.1 ) compared with quinine retreatment ( p<0.001 ) . The introduction of the artemisinin derivatives in routine treatment at this study site in mid 1994 was associated with a reduction in the subsequent incidence of falciparum malaria of 47 (25 - 69)% INTERPRETATION Although environmental changes affect vector numbers , and hence malaria incidence , artemisinin derivatives were found to reduce the transmission potential of falciparum malaria . Widespread introduction of artemisinin derivatives in the treatment of falciparum malaria may prevent the spread of multidrug resistance BACKGROUND Southeast Asia has the most resistant malaria parasites in the world , which severely limits treatment options . There is general acceptance that to combat resistance , combinations of antimalarial drugs that include an artemisinin derivative should be used , and , if possible , these should be formulated in a single tablet . METHODS We did a pilot r and omised study in a tertiary referral hospital in Vietnam to compare the efficacy of 3-day regimens of dihydroartemisinin-trimethoprim-piperaquine ( DHA-TP total dose 4.8/13.6/48 mg/kg , respectively ) with the st and ard antimalarial regimen in Vietnam , artesunate-mefloquine ( A3 M total dose 12/25 mg/kg , respectively ) in non-immune patients with uncomplicated Plasmodium falciparum malaria . 114 patients were r and omised , 76 to DHA-TP and 38 to A3 M . The subsequent open r and omised trial at a Provincial Health Station compared DHA-TP , dihydroartemisinin-piperaquine , and A3 M in 400 patients . In both studies all patients received directly observed therapy and were followed up for 56 days . The primary endpoint was reappearance of P falciparum malaria within 56 days of treatment . Analysis was by intention to treat . FINDINGS The 56-day cure rate in the pilot study , adjusted for reinfections identified by PCR genotyping , was 97.4 % ( 74/76 ) in the DHA-TP group and 100 % ( 38/38 ) in the A3 M group . In the second study , cure rates were similar in the three groups ; DHA-TP 97.4 % ( 153/157 ) , dihydroartemisinin-piperaquine 98.7 % ( 164/166 ) , and A3 M 98.7 % ( 76/77 ) . The DHA-TP and dihydroartemisinin-piperaquine regimens were well tolerated ; fewer than 3 % of patients had side-effects that might have been related to treatment , compared with 16 % of A3 M patients ( p<0.001 ) . No patients were lost to follow-up . INTERPRETATION Dihydroartemisinin-piperaquine is an inexpensive , safe , highly efficacious fixed-dose antimalarial combination treatment that could make an important contribution to the control of multidrug-resistant falciparum malaria Malaria remains a major cause of morbidity and mortality in tropical countries and subtropical regions in the world . Southeast Asia has the most resistant malaria parasites in the world , which has limited treatment options in this region . In response to this situation , short-course artemisinin-based combination therapies ( ACTs ) have been developed . The combination of dihydroartemisinin ( DHA ) and piperaquine ( PQP ) in the form of Artekin has been developed as an alternative to established combinations , such as artesunate-mefloquine , primarily to reduce treatment costs and toxicity . We conducted a study comparing a st and ard treatment for acute uncomplicated falciparum malaria ( artesunate 4 mg/kg/day together with mefloquine 8 mg/kg/day oral route once a day for 3 days ) ( Group A ) and a combination of dihydroartemisinin 40 mg and piperaquine 320 mg in the form of Artekin given once a day for 3 days ( Group B ) to determine safety , efficacy , and tolerability . One hundred and eighty patients were r and omly enrolled at the ratio of 1:2 into groups A : B. All patients had rapid initial clinical and parasitological responses . There were no significant differences in fever clearance time or parasite clearance time between both groups . The 28-day cure rates were high , at 100 % and 99 % , in groups A and B , respectively . We conclude that Artekin was as effective and well-tolerated as artesunate-mefloquine , and can be used alternatively as the current treatment for multidrug-resistant P. falciparum malaria Artemisinin-based combination therapies ( ACTs ) and trimethoprim-sulfamethoxazole ( TS ) prophylaxis are important tools for malaria control , but there are concerns about their effect on gametocytes , the stage of the parasite responsible for transmission . We conducted a longitudinal clinical trial in a cohort of HIV-infected and uninfected children living in an area of high malaria transmission intensity in Ug and a. Study participants were r and omized to artemether-lumefantrine ( AL ) or dihydroartemisinin-piperaquine ( DP ) for all treatments of uncomplicated malaria ( N = 4,380 ) as well as TS prophylaxis for different duration s. The risks of gametocytemia detected by microscopy in the 28 days after antimalarial therapy were compared using multivariate analyses . The risk of gametocyte detection was significantly higher in patients treated with DP compared with AL ( adjusted relative risk = 1.85 , P < 0.001 ) and among children prescribed TS prophylaxis ( adjusted relative risk = 1.76 , P < 0.001 ) . The risk of gametocytemia and its potential for increasing transmission should be considered when evaluating different ACTs and TS prophylaxis for malaria control OBJECTIVE To compare the cost-effectiveness of conventional antimalarial therapy with that of three artemisinin combination treatment regimens in children from Papua New Guinea aged 6 to 60 months . METHODS An incremental cost-effectiveness analysis was performed using data from 656 children with Plasmodium falciparum and /or P. vivax malaria who participated in a large intervention trial in two clinics in northern Papua New Guinea . The children were r and omized to one of the following groups : ( i ) conventional treatment with chloroquine plus sulfadoxine plus pyrimethamine ( CQ+S+P ) ; ( ii ) artesunate plus S plus P ; ( iii ) dihydroartemisinin plus piperaquine ( DHA+PQ ) ; and ( iv ) artemether plus lumefantrine ( A+L ) . For treatment outcomes , World Health Organization definitions were used . The cost of transport between home and the clinic plus direct health-care costs served as a basis for determining each regimen 's incremental cost per incremental treatment success relative to CQ+S+P by day 42 and its cost per life year saved . FINDINGS A+L proved to be the most effective regimen against P. falciparum malaria and was highly cost-effective at 6.97 United States dollars ( US$ ) per treatment success ( about US$ 58 per life year saved ) . DHA+PQ was the most effective regimen against P. vivax malaria and was more cost-effective than CQ+S+P. CONCLUSION A+L and DHA+PQ are highly cost-effective regimens for the treatment of paediatric P. falciparum and P. vivax malaria , respectively , in parts of Papua New Guinea . Future research will be required to determine if these findings hold true for other territories in Asia and Oceania with similar malaria epidemiology BACKGROUND Artemisinin-based combination therapies are now widely recommended as first-line treatment for uncomplicated malaria . However , which therapies are optimal is a matter of debate . We aim ed to compare the short- and longer-term efficacy of 2 leading therapies in a cohort of young Ug and an children . METHODS A total of 351 children aged 6 weeks to 12 months were enrolled and followed up for up to 1 year . Children who were at least 4 months of age , weighted at least 5 kg , and had been diagnosed as having their first episode of uncomplicated malaria were r and omized to receive artemether-lumefantrine or dihydroartemisinin-piperaquine . The same treatment was given for all subsequent episodes of uncomplicated malaria . Recrudescent and new infections were distinguished by polymerase chain reaction genotyping . Outcomes included the risk of recurrent malaria after individual treatments and the incidence of malaria treatments for individual children after r and omization . RESULTS A total of 113 children were r and omized to artemether-lumefantrine and 119 to dihydroartemisinin-piperaquine , result ing in 320 and 351 treatments for uncomplicated falciparum malaria , respectively . Artemether-lumefantrine was associated with a higher risk of recurrent malaria after 28 days ( 35 % vs 11 % ; P = .001 ] ) . When the duration of follow-up was extended , differences in the risk of recurrent malaria decreased such that the overall incidence of malaria treatments was similar for children r and omized to artemether-lumefantrine , compared with those r and omized to dihydroartemisinin-piperaquine ( 4.82 vs 4.61 treatments per person-year ; P = .63 ) . The risk of recurrent malaria due to recrudescent parasites was similarly low in both treatment arms . CONCLUSIONS Artemether-lumefantrine and dihydroartemisinin-piperaquine were both efficacious and had similar long-term effects on the risk of recurrent malaria . Clinical trials registration . NCT00527800 BACKGROUND Combination antimalarial therapy is advocated to improve treatment efficacy and limit selection of drug-resistant parasites . We compared the efficacies of 3 combination regimens in Bobo-Dioulasso , Burkina Faso : amodiaquine plus sulfadoxine-pyrimethamine , which was recently shown to be highly efficacious at this site ; artemether-lumefantrine , the new national first-line antimalarial regimen ; and dihydroartemisinin-piperaquine ( DP ) , a newer regimen . METHODS We enrolled 559 patients > or=6 months of age with uncomplicated Plasmodium falciparum malaria and r and omized them to the 3 regimens . We analyzed the risk of recurrent parasitemia by day 28 and day 42 , both unadjusted and adjusted by PCR methods to distinguish recrudescence and new infection . RESULTS Complete data were available for 517 ( 92.5 % ) of the enrolled subjects . Early treatment failures occurred in 5 patients treated with amodiaquine plus sulfadoxine-pyrimethamine and in 2 patients each treated with the other regimens . The day 28 risk of recurrent parasitemia , unadjusted by genotyping , was significantly higher for patients receiving artemether-lumefantrine than for patients receiving amodiaquine plus sulfadoxine-pyrimethamine ( 20.1 % vs. 6.2 % ; risk difference , 13.8 % ; 95 % confidence interval , 7.0%-20.7 % ) or dihydroartemisinin-piperaquine ( 20.1 % vs. 2.2 % ; risk difference , 17.9 % ; 95 % confidence interval , 11.6%-24.1 % ) . Similar differences were seen for children < 5 years of age ( 54 % of the study population ) and when outcomes were extended to 42 days . Significant differences were not seen between outcomes for patients receiving amodiaquine plus sulfadoxine-pyrimethamine and outcomes for those receiving dihydroartemisinin-piperaquine . Recrudescences were uncommon ( occurring in < 5 % of patients ) in all treatment groups . No serious adverse events were noted . CONCLUSIONS All regimens were highly efficacious in clearing infection , but considering the risks of recurrent malaria after therapy , the amodiaquine plus sulfadoxine-pyrimethamine and dihydroartemisinin-piperaquine regimens were more efficacious than the artemether-lumefantrine regimen ( the new national regimen in Burkina Faso ) for the treatment of uncomplicated P. falciparum malaria OBJECTIVE To determine the efficacy and safety of oral dihydroartemisinin-piperaquine ( DP , Artekin ) in the treatment of uncomplicated Plasmodium falciparum malaria in southern Laos . METHODS An open , r and omized clinical trial of oral artesunate-mefloquine ( AM ) vs. DP in 220 patients with acute uncomplicated falciparum malaria in Savannakhet Province , Laos . RESULTS The 42-day cure rates ( 95 % CI ) , as determined by survival analysis and adjusted for reinfection , were excellent and similar for the two groups [ 99 (94 - 100)% and 100 (100 - 100)% for AM and DP , respectively ] . The median ( range ) fever and parasite clearance times for the AM and DP groups were also similar [ 20 ( 4 - 63 ) h and 2 ( 1 - 4 ) days vs. 20 ( 7 - 57 ) and 2 ( 1 - 4 ) days , logrank P = 0.4 and 0.17 , respectively ] . There were more patients with at least one potential side effect following treatment in the AM group when compared with the DP group [ 64/110 ( 58 % ) vs. 48/110 ( 44 % ) , respectively , P = 0.031 ] . CONCLUSION Dihydroartemisinin-piperaquine did not have superior efficacy to AM for the treatment of uncomplicated falciparum malaria in Laos but was associated with fewer adverse effects In Rw and a , amodiaquine+sulfadoxine/pyrimethamine ( AQ+SP ) is the current first-line treatment for malaria , introduced in 2001 as an interim strategy before the future deployment of an artemisinin-based combination treatment ( ACT ) . Dihydroartemisinin/piperaquine ( DHA-PQP ) is a new co-formulated and well tolerated ACT increasingly used in Southeast Asia where it has proved to be highly effective against Plasmodium falciparum malaria . We tested the efficacy , safety and tolerability of DHA-PQP in children with uncomplicated P. falciparum malaria . A r and omised , open trial was carried out in 2003 - 2004 . Seven hundred and sixty-two children aged 12 - 59 months with uncomplicated P. falciparum malaria were r and omly allocated to one of the following treatments : amodiaquine+artesunate ; AQ+SP ; or DHA-PQP . Patients were followed-up until Day 28 after treatment . Adverse events and clinical and parasitological outcomes were recorded . Children treated with DHA-PQP or AQ+AS had a significantly higher cure rate compared with those treated with amodiaquine+sulfadoxine/pyrimethamine ( 95.2 % and 92.0 % vs. 84.7 % , respectively ) . Parasite clearance was significantly faster in children treated with DHA-PQP and AQ+AS compared with those treated with amodiaquine+sulfadoxine/pyrimethamine . The frequency of adverse events was significantly lower in patients treated with DHA-PQP than in those treated with combinations containing amodiaquine . A 3-day treatment with DHA-PQP proved to be efficacious with a good safety and tolerability profile and could be a good c and i date for the next first-line treatment Artemether-lumefantrine ( AL ) and dihydroartemisinin-piperaquine ( DP ) are highly efficacious antimalarial therapies in Africa . However , there are limited data regarding the tolerability of these drugs in young children . We used data from a r and omized control trial in rural Ug and a to compare the risk of early vomiting ( within one hour of dosing ) for children 6 - 24 months of age r and omized to receive DP ( n = 240 ) or AL ( n = 228 ) for treatment of uncomplicated malaria . Overall , DP was associated with a higher risk of early vomiting than AL ( 15.1 % versus 7.1 % ; P = 0.007 ) . The increased risk of early vomiting with DP was only present among breastfeeding children ( relative risk [ RR ] = 3.35 , P = 0.001 ) compared with children who were not breastfeeding ( RR = 1.03 , P = 0.94 ) . Age less than 18 months was a risk factor for early vomiting independent of treatment ( RR = 3.27 , P = 0.02 ) . Our findings indicate that AL may be better tolerated than DP among young breastfeeding children treated for uncomplicated malaria |
1,288 | 28,813,703 | Conclusions : This meta- analysis suggests that the entacapone used as adjuvant therapy to LD is effective in the management of later PD with fluctuation .
However , patients on entacapone had a higher frequency of adverse events than those on placebo but no occurrence of severe adverse reactions | Aims : To assess the efficacy and safety of adjuvant treatment with entacapone in the treatment of later Parkinson ’s disease ( PD ) patients with motor fluctuation . | OBJECTIVES --To establish , in a double blind manner , the antiparkinsonian effects of repeated dosing with entacapone , a peripheral COMT inhibitor . METHODS --A one month , cross over study was conducted . During the two four-week treatment periods , entacapone ( 200 mg ) or placebo was given with each levodopa dose four to 10 times daily . Motor responses were repeatedly quantified using the motor part of UPDRS . Plasma levodopa and its metabolites were measured . RESULTS --Entacapone prolonged the availability of levodopa in the plasma and thus to the brain by decreasing its peripheral O-methylation and slowing its elimination rate , without affecting the maximum plasma levodopa concentration or the time to maximum concentration . Corresponding with the pharmacokinetic findings , entacapone prolonged the duration of motor response to an individual levodopa/DDC inhibitor dose by 34 minutes ( 24 % , P = 0.001 ) and dyskinesiae by 39 minutes ( 37 % , P = 0.002 ) compared with placebo , without affecting their magnitude or starting time . Entacapone treatment result ed in a reduction of 16 % in the mean total daily levodopa dose due to dyskinesiae . Also , according to the home diaries , the mean daily " on " time increased by 2.1 hours compared with placebo , despite the lowered mean levodopa intake . CONCLUSION --The efficacy of repeated entacapone dosing as an adjuvant to levodopa/DDC inhibitor treatment for Parkinson 's disease with levodopa related fluctuations is verified Motor fluctuations associated with levodopa therapy are common problems encountered in the long‐term treatment of Parkinson 's disease ( PD ) . Entacapone , a peripherally acting , reversible inhibitor of catechol‐O‐methyltransferase , slows the elimination of levodopa in humans by reducing the formation of 3‐O‐methyldopa . We conducted a placebo‐controlled , double‐blind , parallel‐group , multicenter trial of entacapone in PD patients with motor fluctuations . Two hundred five patients were r and omized to receive either entacapone 200 mg or matching placebo with each dose of levodopa and were followed for 24 weeks . The primary measure of efficacy was the change in percentage of “ on ” time ( relief of parkinsonism ) while awake , as recorded by subjects at home in diaries completed at 30‐minute intervals . At baseline , patients averaged approximately 10 hours of “ on ” time per day while awake ( 60.5 % “ on ” time ) , and entacapone treatment increased the percent “ on ” time by 5.0 percentage points . The effect of entacapone was more prominent in patients with a smaller percent “ on ” time ( < 55 % ) at baseline , and increased as the day wore on . Entacapone is effective at increasing the duration of response to levodopa and at relieving parkinsonism in patients experiencing motor flucturations and was well tolerated during the 24 weeks of treatment OBJECTIVE The objective of this study was to examine the cost-effectiveness of a complementary treatment with entacapone versus usual care only in patients with Parkinson 's disease . METHODS The setting for this study was the Netherl and s. A Markov process model was constructed to model the average quality -adjusted life years ( QALYs ) and the costs of both treatments . The model examined a period of 5 years in order to capture the influence of symptom improvement and disease progression . Data for the construction of the model were derived from published literature , including large , multicenter , r and omized clinical trials in patients with end-of-dose motor fluctuations . Costs were obtained from published sources . RESULTS The results of the baseline analysis showed that the use of entacapone as complementary therapy in Parkinson 's disease slightly decreased the total average discounted costs from NLG 111,317 to NLG 110,038 , while effectiveness increased from 2.42 to 2.56 QALYs ( a 6 % increase ) . In addition , entacapone substantially increased time without severe fluctuations by 0.63 years . Sensitivity analyses confirmed the robustness of these findings . CONCLUSION The study shows that entacapone is a cost-effective treatment in patients with Parkinson 's disease : entacapone yields higher effectiveness in terms of both effectiveness measures ( time without severe fluctuations and QALYs ) , while costs remain quite similar to those for usual care . The additional drug costs for entacapone are offset by reductions in other costs Summary . Objectives : To evaluate the tolerability , safety and efficacy of Stalevo ® ( carbidopa , levodopa and entacapone ) in Parkinson ’s disease ( PD ) . Background : Levodopa provides the most effective symptom control for the treatment of Parkinson ’s disease ( PD ) . However , its long-term use is limited by the development of motor complications such as wearing-off . Catechol-O-methyltransferase ( COMT ) inhibitors such as entacapone extend the plasma half-life of levodopa and reduce ‘ off ’ time . Stalevo is a new levodopa product that combines carbidopa , levodopa and entacapone in one tablet . Clinical studies have not been reported with this compound . Design methods : An open-label , multi-center US trial evaluated 169 consecutive PD patients experiencing end-of-dose wearing-off , with ( n = 39 ) and without ( n = 130 ) mild dyskinesia . Patients were switched from immediate-release carbidopa/levodopa to Stalevo and were treated for four weeks . Assessment s included tolerability measures , adverse events profile , the disease-specific quality of life instrument PDQ-39 , UPDRS parts II , III , and question 39 and investigator and patient global clinical assessment s. Results : 14 subjects ( 8 % ) discontinued treatment with Stalevo , of which 12 ( 7 % ) were due to adverse events . 11/130 ( 8.5 % ) subjects developed new onset dyskinesia and 17/39 ( 43.6 % ) of patients with existing dyskinesia reported a worsening in their dyskinesia . However , this was managed by a change in dose in 21.4 % of patients and in another 10.7 % dyskinesias resolved without any need for dose adjustment . Other side effects were infrequent and mild , the most common being nausea ( 12.4 % ) dizziness ( 6.5 % ) and somnolence ( 6.5 % ) . Stalevo treatment result ed in significant improvements in PDQ-39 and UPDRS ( II + III ) scores ( p < 0.001 ) . Assessment of ‘ off ’ time demonstrated a reduction in off time in 32 % of patients , compared with an increase in 7 % of patients . Improvements were noted by both investigator ( 68.1 % ) and patient ( 68.6 % ) assessment s. Conclusions : Switching PD patients experiencing wearing-off from carbidopa/levodopa therapy to Stalevo was safe , well tolerated and result ed in clinical improvement Summary . The efficacy and tolerability of entacapone was investigated in a r and omized , double-blind , placebo-controlled , 3-month study of 162 patients with Parkinson 's disease ( PD ) treated with levodopa and a dopamine agonist and experiencing wearing-off motor fluctuations . Patients were r and omized in a 3 : 2 ratio to entacapone 200 mg or placebo , administered with each dose of levodopa . Efficacy was judged on the improvement of “ on ” and “ off ” time while awake ( Patient Diary and UPDRS part IV Item 39 ) , Investigators ' Global Assessment , the SF-36 Health Survey , and changes in levodopa dosages . Patients were monitored for adverse events , laboratory safety and vital signs throughout the study . Improvements in “ on ” time as assessed using patient diary data showed a trend in favour of entacapone , however these did not reach statistical significance . “ Off ” time while awake ( UPDRS part IV Item 39 ) showed an improvement of at least one category in 36 % of entacapone-treated patients , compared with 22 % in the control group ( p = 0.0038 ) . The proportion of patients showing an improvement at the Investigators ' Global Assessment was significantly higher ( p = 0.0006 ) in the entacapone-treated group of patients . Also , the proportion of patients with a reduction in their daily levodopa dose was significantly higher ( p = 0.02 ) in the entacapone group ( 28 % ) compared with placebo ( 13 % ) . As expected , the most frequent adverse events were dopamine-mediated ( dyskinesia : entacapone 31 % versus placebo 13 % ) , and harmless urinary discoloration . The modest increase in dyskinesias could be readily managed by levodopa down-adjustment , and , at study end there was no significant difference for the UPDRS “ overall dyskinesia score ” between entacapone and placebo . In conclusion , although the primary efficacy variable did not reach statistical significance , the present results demonstrate that entacapone provides additional antiparkinsonian benefits to levodopa therapy and is well tolerated in levodopa-treated PD patients experiencing wearing-off motor fluctuations despite adjunct dopamine agonist therapy Entacapone is a catechol-O-methyltransferase ( COMT ) inhibitor used as an adjunct to levodopa/dopa decarboxylase inhibitors in the treatment of Parkinson 's disease . Entacapone increases the bioavailability and reduces the daily variation of plasma levodopa when administered with st and ard levodopa preparations . These parameters were studied when entacapone was administered with a controlled-release levodopa preparation after repeated administrations throughout the day in 16 healthy male volunteers . On 2 test days , 200 mg entacapone or placebo was administered 4 times during the day at 4-hour intervals concomitantly with a single dose of controlled-release levodopa/carbidopa 100 mg/25 mg ( Sinemet CR ) . Plasma levodopa , 3-O-methyldopa ( 3-OMD ) , and carbidopa concentrations were measured before intake of the medication and then every 30 minutes for 16 hours ( until midnight ) , and less frequently up to 24 hours after the first levodopa dose . The minimum , maximum , and average concentration of levodopa ; the daily variation of levodopa concentration ; and the area under the time concentration curve ( AUC ) were calculated . The mean ( ±SD ) plasma levodopa AUC was 39 % ( P = 0.0001 ) higher with entacapone ( 11,802 ± 1454 ng/hour/mL ) compared with placebo ( 8465 ± 927 ng/hour/mL ) . The daily variation of plasma levodopa was reduced by about 25 % with entacapone ( P < 0.01 ) . Entacapone significantly reduced plasma 3-OMD concentration by about 50 % ( P = 0.0001 ) , indicating marked COMT inhibiting activity . There were no differences in plasma carbidopa concentrations . Entacapone significantly increased the bioavailability of levodopa and reduced its daily variation when administered concomitantly with a controlled-release levodopa preparation Objectives – To determine the efficacy and safety of the catechol‐O‐methyltransferase ( COMT ) inhibitor entacapone , used as an adjunct to levodopa , in Parkinson 's disease ( PD ) patients . Patients and methods – In this parallel group , r and omized , double‐blind study , 301 PD patients , the majority with motor fluctuations , received entacapone ( 200 mg ) or placebo with each daily dose of st and ard or controlled‐release ( CR ) levodopa . The 24‐week treatment period was followed by 2 weeks of entacapone withdrawal . Efficacy was determined by home diaries ( ` on ' and ` off ' times ) , Unified Parkinson 's Disease Rating Scale ( UPDRS ) and changes in levodopa dosage , and safety by adverse‐event inquiry , vital signs , electro cardiography ( ECG ) and laboratory tests . Results – In the total population , the UPDRS activities of daily living and motor scores were significantly improved ( P < 0.05 ) by entacapone vs placebo . In fluctuating patients , ` on ' time increased ( 1.7 h ) and ` off ' time decreased ( 1.5 h ) significantly more with entacapone than with placebo ( 0.5 and 0.6 h , respectively ; P < 0.05 ) , and the daily levodopa dose was reduced by 54 mg with entacapone and increased by 27 mg with placebo ( P < 0.05 ) . Entacapone benefit was lost on withdrawal . Entacapone efficacy was comparable between patients using CR and st and ard levodopa preparations . Increased dyskinesias ( entacapone 34 % , placebo 26 % ) and nausea ( 10 and 5 % , respectively ) , mostly occurring shortly after treatment initiation , were generally managed by reducing the levodopa dose . Diarrhoea ( entacapone 8 % , placebo 4 % ) was seldom severe . There were no differences in vital signs , ECG or laboratory results . Conclusion – Entacapone is an effective and safe levodopa extender and enhancer , improving the symptomatic efficacy of levodopa in PD and adding to the patients ' benefit Abstract Levodopa ( LD ) provides the most effective symptomatic treatment for Parkinson 's disease ( PD ) . Long-term treatment with LD , however , is often associated with the development of response fluctuations . Previous evidence suggests that the short half-life of LD is a major contributor to the development of response fluctuations and the wearing-off phenomenon in particular . Entacapone , a peripheral catechol-O-methyltransferase inhibitor has been shown to reduce OFF time and increase ON time in several therapeutic trials on PD patients treated with LD experiencing motor fluctuations . However , data are missing on the tolerability and efficacy of entacapone in elderly PD patients . This is of particular relevance , as most PD patients develop LD-related motor fluctuations after several years of disease duration . Here we report that addition of entacapone in a group of 45 elderly PD patients with LD-related motor fluctuations is well tolerated and efficacious in reducing the time , frequency and severity of the OFF periods . These data suggest that the drug can be used safely and efficaciously in elderly PD patients Objective : To study the effect of entacapone , a specific peripherally acting catechol-O-methyltransferase ( COMT ) inhibitor used in combination with levodopa treatment , in cases of Parkinson ’s disease with both fluctuating and non-fluctuating response to treatment . Methods : A r and omised , placebo controlled , double blind , six month study was undertaken in 172 fluctuating and 128 non-fluctuating patients . The clinical efficacy and safety of 200 mg entacapone given with each daily levodopa dose was studied . Efficacy was examined using home diaries , the unified Parkinson disease rating scale ( UPDRS ) , and recording of daily levodopa dose . Results : The primary efficacy variable for fluctuating patients —the proportion of daily ON time — showed a significant increase compared with placebo ( p < 0.05 ) . The absolute ON time ( mean ( SD ) ) increased from 9.5 ( 2.5 ) to 10.8 ( 2.4 ) hours ( p < 0.01 ) , and the daily OFF time was correspondingly reduced from 7.0 ( 2.6 ) to 5.9 ( 2.5 ) hours ( p < 0.05 v placebo ) . This improvement was achieved despite a reduction in daily levodopa requirements . The effect was rapidly lost on withdrawal of entacapone . In non-fluctuating patients , the primary efficacy measure was part II of the UPDRS ( activities of daily living ; ADL ) . In this group of patients , ADL scores improved in the entacapone group ( p < 0.01 v placebo ) , and there was also a 40 mg reduction in levodopa requirement ( p < 0.01 v placebo ) . Entacapone was well tolerated by both fluctuating and non-fluctuating patients . Conclusions : The ability of entacapone to provide additional benefits to levodopa treatment in increasing ON time in fluctuating Parkinson ’s disease patients was confirmed . A novel finding was that patients without fluctuations also obtained benefit from the addition of entacapone to their levodopa treatment , as evidence d by improved ADL scores and a relatively reduced levodopa requirement BACKGROUND Despite the known benefit of levodopa in reducing the symptoms of Parkinson 's disease , concern has been expressed that its use might hasten neurodegeneration . This study assessed the effect of levodopa on the rate of progression of Parkinson 's disease . METHODS In this r and omized , double-blind , placebo-controlled trial , we evaluated 361 patients with early Parkinson 's disease who were assigned to receive carbidopa-levodopa at a daily dose of 37.5 and 150 mg , 75 and 300 mg , or 150 and 600 mg , respectively , or a matching placebo for a period of 40 weeks , and then to undergo withdrawal of treatment for 2 weeks . The primary outcome was a change in scores on the Unified Parkinson 's Disease Rating Scale ( UPDRS ) between baseline and 42 weeks . Neuroimaging studies of 142 subjects were performed at baseline and at week 40 to assess striatal dopamine-transporter density with the use of iodine-123-labeled 2-beta-carboxymethoxy-3-beta-(4-iodophenyl)tropane ( [123I]beta-CIT ) uptake . RESULTS The severity of parkinsonism increased more in the placebo group than in all the groups receiving levodopa : the mean difference between the total score on the UPDRS at baseline and at 42 weeks was 7.8 units in the placebo group , 1.9 units in the group receiving levodopa at a dose of 150 mg daily , 1.9 in those receiving 300 mg daily , and -1.4 in those receiving 600 mg daily ( P<0.001 ) . In contrast , in a sub study of 116 patients the mean percent decline in the [123I]beta-CIT uptake was significantly greater with levodopa than placebo ( -6 percent among those receiving levodopa at 150 mg daily , -4 percent in those receiving it at 300 mg daily , and -7.2 percent among those receiving it at 600 mg daily , as compared with -1.4 percent among those receiving placebo ; 19 patients with no dopaminergic deficits on the baseline scans were excluded from the analysis ) ( P=0.036 ) . The subjects receiving the highest dose of levodopa had significantly more dyskinesia , hypertonia , infection , headache , and nausea than those receiving placebo . CONCLUSIONS The clinical data suggest that levodopa either slows the progression of Parkinson 's disease or has a prolonged effect on the symptoms of the disease . In contrast , the neuroimaging data suggest either that levodopa accelerates the loss of nigrostriatal dopamine nerve terminals or that its pharmacologic effects modify the dopamine transporter . The potential long-term effects of levodopa on Parkinson 's disease remain uncertain To determine the efficacy , safety and tolerability of nebicapone , a new catechol‐O‐methyltransferase inhibitor for the treatment of motor fluctuations in Parkinson 's disease ( PD ) , we conducted a multicenter , r and omized , 8‐week double‐blind , placebo‐ and active‐controlled , parallel‐group study comparing nebicapone 50 mg , 100 mg , or 150 mg , entacapone 200 mg ( active control ) or placebo administered concomitantly with levodopa/carbidopa or levodopa/benserazide . Two hundred and fifty‐two PD patients with motor fluctuations treated with levodopa/carbidopa or levodopa/benserazide ( 4–8 daily doses ) were enrolled and 250 patients were eligible for intention‐to‐treat ( ITT ) analysis on the basis of having at least one efficacy assessment . The primary endpoint was 8‐week change from baseline in absolute “ Off ” time duration noted in self‐scoring diaries . At 8 weeks of treatment the mean daily “ Off ” time decreased significantly compared to placebo for nebicapone 150 mg ( −106 min ; 95%CI : −192 ; −21 ) and entacapone 200 mg ( −81 min ; 95%CI : −142 ; −19 ) . The decrease in “ Off ” time with nebicapone 50 mg or 100 mg did not reach statistical significance . Treatment‐emergent adverse events were reported by 32 % to 49 % of patients in any treatment group , with no observed dose relationship in the nebicapone groups . Clinical ly relevant elevations in aspartate transaminase ( AST ) and /or alanine transaminase ( ALT ) were observed in 4 of 46 patients with the nebicapone 150 mg dose . The results of this study show that nebicapone 150 mg is efficacious for the treatment of motor fluctuations in PD patients . However , the risk of increasing liver transaminases and its clinical ly relevance deserves further evaluation Objectives Perampanel is a selective and noncompetitive & agr;-amino-3-hydroxy-5-methylisoxazole propionic acid – type glutamate receptor antagonist that improves motor symptoms in animal models of Parkinson disease ( PD ) . The aim of this study was to assess the efficacy and tolerability of perampanel in L-dopa – treated patients with moderately severe PD and motor fluctuations using an active comparator study design . Methods This was a prospect i ve , r and omized , double-blind , 3-arm , parallel-group , controlled study assessing the effects of perampanel ( 4 mg/d ) , placebo , or entacapone ( 200 mg with each dose of L-dopa ) in 723 L-dopa – treated patients with PD with “ OFF ” problems . The primary outcome measure was the change from baseline in mean total daily OFF time based on diaries . Secondary end points included change from baseline in Unified Parkinson ’s Disease Rating Scale part II while OFF , Unified Parkinson ’s Disease Rating Scale part III while “ ON , ” and mean total daily ON time without dyskinesias or with nontroublesome dyskinesias . Results In total , 480 patients ( 66.4 % ) completed the study , which was terminated early after negative results of 2 other large placebo-controlled studies became available . Perampanel was not superior to placebo on any efficacy end point , whereas entacapone was superior to placebo on the primary end point ( P = 0.034 ) and most secondary outcomes . Perampanel was generally well tolerated . Conclusions Perampanel ( 4 mg/d ) was well tolerated but did not have a clinical ly significant effect in improving motor symptoms of L-dopa – treated patients with moderately advanced PD and motor fluctuations . These patients did respond to the active comparator , entacapone , confirming the validity of the findings despite the early termination of the study We conducted a multicenter r and omized , placebo-controlled double-blind parallel-group study in Japanese Parkinson 's disease ( PD ) patients with wearing-off motor fluctuations to determine the clinical efficacy and safety of entacapone as an adjunct to concomitant treatment with levodopa and a dopa decarboxylase inhibitor ( DCI ) . We r and omized 341 patients to receive entacapone 100 or 200 mg or placebo per dose of levodopa/DCI for 8 weeks . The primary efficacy variable was on time change while awake , determined by patients ' diaries . Mean baseline on time in each group was approximately 8 hours . Mean on time change at final assessment was 1.4 hours each for entacapone 100-mg and 200-mg groups and by 0.5 hours for the placebo group ( P < 0.05 ) . The two entacapone doses were equally efficacious . Adverse events occurred in 79 patients ( 69.9 % ) in placebo , 82 ( 72.6 % ) in 100 mg , and 98 ( 86.0 % ) in 200 mg . The most common adverse event with entacapone was an increase in dyskinesias . The overall safety profile was satisfactory in both entacapone groups . In conclusion , both entacapone 100 and 200 mg were equally effective in increasing on time of PD patients with wearing-off fluctuations , although the safety and tolerability profile appeared more favorable for the 100-mg dose Objectives – To compare the efficacy of levodopa/dopa decarboxylase inhibitor ( DDCI ) plus entacapone with levodopa/DDCI plus placebo on measures of parkinsonian disability and health‐related quality of life ( QoL ) in subjects with Parkinson 's disease ( PD ) experiencing motor fluctuations Entacapone is a potent , reversible and orally active inhibitor of catechol-O-methyltransferase . This open multicenter study evaluated the efficacy , safety and tolerability of entacapone as adjunct therapy to levodopa/dopa decarboxylase inhibitor ( ≧3 daily doses ) in patients with idiopathic Parkinson ’s disease and end-of-dose motor fluctuations . The 8-week study included 489 patients under conditions of typical daily medical practice . Patients were treated with a 200-mg fixed dose of entacapone administered with each scheduled dose of levodopa to a maximum of 10 doses per day . Other antiparkinsonian medication should have been stable for at least 1 month . The primary efficacy criteria were : ( 1 ) Part II ( activities of daily living , ADL ) of the Unified Parkinson ’s Disease Rating Scale ( UPDRS ) , ( 2 ) the reduction of ‘ off ’ time during the daily waking period as assessed by the percentage of patients improving by at least one category at Item 39 of Part IV of the UPDRS . Secondary outcome measures included : ( 1 ) the investigator ’s global assessment of change , ( 2 ) quality of life ( QoL ) was assessed using the Parkinson ’s Disease Question naire ( PDQ-39 ) . Adverse events , vital signs and liver enzymes were monitored at weeks 2 and 8 . The baseline mean score for ADL was 10.5 ( ±7.04 ) , which decreased to 8.5 ( ±6.37 ) at the end of the study ( p < 0.0001 ) . Compared to baseline , 40.8 % of patients experienced a reduction in ‘ off ’ time during the waking period ; this improvement was highly significant ( p < 0.0001 ) . A reduction in the daily dose of levodopa was observed in 35.8 % of patients ( mean decrease 209 ± 149 mg ) . QoL was improved by a mean of 10 % in all categories of the PDQ-39 ( p < 0.001 ) , except social support and cognition . This improvement was statistically significant ( p < 0.001 ) . The dyskinesia score ( UPDRS Item 32 ) was decreased significantly from 2.3 to 2.1 from baseline to end of study ( p < 0.001 ) , although 52.7 % of patients reported levodopa-induced dyskinesia as an adverse event . There was no case of increased liver enzymes . The study results confirm that the excellent risk/benefit ratio seen in phase III controlled studies can be seen in daily neurological practice . Moreover , the study suggests that the benefits of entacapone are associated with a significant improvement in Article abstract –Catechol-O-methyltransferase ( COMT ) metabolizes a portion of administered levodopa and thus makes it unavailable for conversion to dopamine in the brain . In an open-label trial , we examined the effects of entacapone , a peripheral inhibitor of COMT , administered acutely or for 8 weeks , on the pharmacokinetics and pharmacodynamics of levodopa in 15 parkinsonian subjects with a fluctuating response to levodopa . Acutely and chronically administered entacapone similarly decreased the plasma elimination of orally and intravenously administered levodopa . Absorption of levodopa was minimally affected . During chronic entacapone treatment , daily levodopa dosages were reduced by 27 % yet mean plasma levodopa concentrations were increased by 23 % . Plasma 3-O-methyldopa concentrations were decreased by 60 % . Entacapone increased the duration of action of single doses of levodopa by a mean of 56 % . The percent of the day “ on ” after 8 weeks of entacapone treatment was 77 % ; it dropped to 44 % upon withdrawal of entacapone . We conclude that inhibition of COMT by entacapone increases the plasma half-life of levodopa and augments the antiparkinsonian effects of single and repeated doses of levodopa Two common primary efficacy outcome measures in Parkinson 's disease ( PD ) are change in Unified Parkinson 's Disease Rating Scale ( UPDRS ) scores in early PD and change in " off " time in patients with motor fluctuations . Defining the minimal clinical ly important change ( MCIC ) in these outcome measures is important to interpret the clinical relevance of changes observed in clinical trials and other situations . We analyzed data from 2 multicenter , placebo-controlled , r and omized clinical trials of rasagiline ; TEMPO studied 404 early PD subjects , and PRESTO studied 472 levodopa-treated subjects with motor fluctuations . An anchor-based approach using clinical global impression of improvement ( CGI-I ) was used to determine MCIC for UPDRS scores and daily " off " time . MCIC was defined as mean change in actively treated subjects rated minimally improved on CGI-I. Receiver operating characteristic ( ROC ) curves defined optimal cutoffs discriminating between changed and unchanged subjects . MCIC for improvement in total UPDRS score ( parts I-III ) in early PD was determined to be -3.5 points based on mean scores and -3.0 points based on ROC curves . In addition , we found an MCIC for reduction in " off " time of 1.0 hours as defined by mean reduction in " off " time in active treated subjects self-rated as minimally improved on CGI-I minus mean reduction in " off " time in placebo-treated subjects self-rated as unchanged ( 1.9 - 0.9 hours ) . We hypothesize that many method ological factors can influence determination of the MCIC , and a range of values is likely to emerge from multiple studies Objective : To study the effect and safety of entacapone as an adjunct to levodopa treatment in patients with PD with wearing-off motor fluctuations . Background : Entacapone is a catechol-O-methyltransferase ( COMT ) inhibitor that has been shown to increase the area under the concentration-time curve of plasma levodopa by decreasing its systemic elimination , thereby promoting and improving therapeutic response to it . Methods : A total of 171 parkinsonian patients with wearing-off-type motor fluctuations participated in a 6-month r and omized , placebo-controlled , double-blind , parallel-group study . The extent of therapeutic response was elicited in the first h and with home diary recordings of " on " and " off " times by the patient and with Unified Parkinson 's Disease Rating Scale scoring by the examiner . The patients took either 200 mg entacapone or identical placebos concomitantly with each daily levodopa dose ( four to 10 times a day ) . Results : Patients ' home diaries indicated that entacapone increased the mean ( ± SD ) " on " time significantly ( 9.3 ± 2.2 to 10.7 ± 2.2 hours ; p < 0.01 ) and correspondingly decreased the " off " time significantly ( 5.3 ± 2.2 to 4.2 ± 2.2 hours ; p < 0.001 ) . The average benefit derived from a daily levodopa dose as related by the patients was increased significantly ( p < 0.01 ) . The daily levodopa dose was reduced significantly in the entacapone group , the difference between the groups being 102 mg ( p < 0.01 ) . The entacapone-derived increase in the benefit from levodopa was lost almost completely following its withdrawal . Entacapone was well tolerated . Dopaminergic adverse events , which increased , were ameliorated by reducing the levodopa dose . Diarrhea was the most common nondopaminergic adverse event . Conclusions : Long-term entacapone treatment effectively prolonged the beneficial response to levodopa in parkinsonian patients with the wearing-off phenomenon . The improvement occurred irrespective of the reduction of the levodopa dose The Unified Parkinson 's Disease Rating Scale ( UPDRS ) is the main outcome measure in clinical trials of Parkinson 's disease ( PD ) . The minimal change that represents a clinical ly meaningful improvement is unknown . The objective of this study was to determine the minimal change on the UPDRS that represents a clinical ly meaningful improvement in early PD after 6 months of treatment . Data from two independent r and omized treatment trials over 6 months involving 603 patients with de novo PD were analyzed to determine the minimal clinical ly important change ( MCIC ) , referred to the status before treatment , for the UPDRS motor , activities of daily living ( ADL ) , and total scores . An anchor-based method using ratings on a seven-point global clinical improvement was used . A change of five points on the UPDRS motor part was found to be the most appropriate cutoff score for all Hoehn and Yahr stages I to III , and a change of eight points for the UDPRS total score . For the UDPRS ADL score , an MCIC of two points for Hoehn and Yahr stages I/I.5 and II and of three points for Hoehn and Yahr stage II.5/III was the most appropriate cutoff score . These data give the first estimate for cutoffs defining clinical ly important changes in UPDRS ADL and motor scores . Further studies using larger data bases from more diverse study population s are encouraged to better define and solidify the MCIC for the UPDRS A dose-response study of the effects of entacapone on the pharmacokinetics and metabolism of levodopa and on the clinical response to levodopa was carried out in 20 parkinsonian patients with levodopa-related fluctuations . A r and omized , double-blind , single- grade d-dose , crossover design of five 1-day treatment periods each 1 week apart was used . Entacapone ( 50 , 100 , 200 , or 400 mg ) or placebo was given at 8 a.m. with the patient 's individual dose of levodopa/dopa decarboxylase inhibitor . The inhibition of soluble catechol-O-methyltransferase ( S-COMT ) in red blood cells ( RBCs ) and plasma concentrations of levodopa , its metabolites , and entacapone were measured and motor responses were quantified at 30min intervals using the motor part of the Unified Parkinson 's Disease Rating Scale . Entacapone brought about a dose-dependent decrease in S-COMT activity in the RBCs , maximally by 48 % at 400 mg . With a 200-mg dose of entacapone , the area under the plasma concentration-time curve ( AUC ) and half-life of levodopa increased ( p < 0.001 ) ; the AUCs of 3-O-methyldopa and homovanillic acid decreased ( p = 0.01 and p < 0.001 , respectively ) and that of 3,4-dihydroxyphenylacetic acid increased ( p < 0.001 ) . Entacapone prolonged the duration of the motor response to levodopa by 33 min ( p = 0.04 ) and dyskinesias by 45 min ( p = 0.003 ) without affecting their magnitude ; the highest increase in duration of these responses occurred with 200 mg of entacapone . Thus , on pharmacokinetic and clinical grounds , the 200-mg dose of entacapone was the most effective . Dose-related responses to entacapone demonstrated its value in the treatment of parkinsonian patients with levodopa-related fluctuations by prolonging the antiparkinsonian response to the levodopa dose Objective : To investigate the effects of nebicapone , a new catechol-O-methyltransferase ( COMT ) inhibitor , on levodopa pharmacokinetics , COMT activity , and motor fluctuations in Parkinson disease in comparison to placebo and entacapone . Methods : R and omized , double-blind , placebo-controlled , 4-way crossover study consisting of 4 treatment periods ( 6 - 9 days duration each ) in 19 patients ( 65.3 ± 8.5 years ) treated with carbidopa/levodopa 3 to 7 times per day . Nebicapone/entacapone/placebo and carbidopa/levodopa doses were administered concomitantly . At the end of each period , a levodopa test was performed , and levodopa and 3-O-methyldopa levels and COMT activity were assayed . Results : After 75 mg nebicapone , 150 mg nebicapone , and 200 mg entacapone , levodopa area under the plasma concentration time curve significantly increased 28.1 , 48.4 , and 33.3 % , and 3-O-methyldopa area under the plasma concentration time curve significantly decreased 59.2 , 70.8 , and 59.1 % , respectively . Peak COMT inhibition was similar between active treatments , but extent of COMT inhibition was more sustained with 75 and 150 mg nebicapone than with 200 mg entacapone . After the levodopa test doses , ON time significantly increased 29 minutes with 75 mg nebicapone , 45 minutes with 150 mg nebicapone , and 16 minutes with 200 mg entacapone . Patients ' diaries showed a decrease in daily OFF time of 109 minutes with 75 mg nebicapone , 103 minutes with 150 mg nebicapone , and 71 minutes with 200 mg entacapone , and an increase in daily ON time of 74 , 101 , and 74 minutes , respectively . Treatments were generally well tolerated and safe ; no relevant changes in liver function tests were reported . Conclusions : Nebicapone , a new COMT inhibitor , significantly decreased COMT activity , increased systemic exposure to levodopa , and improved motor response . Nebicapone deserves further evaluation in larger sample s of patients |
1,289 | 17,636,812 | Improvement with use of opioid analgesia was verified in variables patient comfort , reduction of pain , changes in physical examination .
AUTHORS ' CONCLUSIONS The review provide some evidence to support the notion that the use of opioid analgesics in patients with acute abdominal pain is helpful in terms of patient comfort and does not retard decisions to treat | BACKGROUND For decades , analgesia for patients with acute abdominal pain was withheld until a definitive diagnosis was established for fear of masking the symptoms , changing physical findings or ultimately delaying diagnosis and treatment of a surgical condition .
This non- evidence -based approach has been challenged by recent studies demonstrating that the use of analgesia in the initial evaluation of patients with acute abdominal pain leads to significant pain reduction without affecting diagnostic accuracy .
However , early administration of analgesia to such patients can greatly reduce their pain and does not interfere with a diagnosis , which may even be facilitated due to the severity of physical symptoms being reduced .
OBJECTIVES To determine if the currently available evidence supports the use of opioid analgesia in patient management with acute abdominal pain ; and to assess changes in a patient comfort while awaiting definitive diagnosis and final treatment decisions . | OBJECTIVE To evaluate the effects of intravenous morphine on pain reduction , physical examination , and diagnostic accuracy in children with acute abdominal pain . METHODS A r and omized , double-blind , placebo-controlled clinical trial was conducted at an emergency department of a tertiary care children 's hospital . Children aged 5 - 18 years with abdominal pain of < or = 5 days ' duration , pain score > or = 5 on a 0 - 10 visual analog scale , and need for surgical evaluation were eligible . Following the initial assessment , patients were r and omized to receive either 0.1 mg/kg morphine or an equal volume of saline . The pediatric emergency medicine physician and surgical consultant independently recorded the areas of tenderness to palpation and percussion , and their diagnoses before the study medication and 15 to 30 minutes later . RESULTS Sixty patients were enrolled , and 29 received morphine and 31 received saline . The demographic characteristics between the two groups were similar . The median reduction of pain score between the two study groups was 2 ( 95 % CI = 1 to 4 ; p = 0.002 ) . There was no significant change in the areas of tenderness in both study groups . Children with surgical conditions had persistent tenderness to palpation and /or percussion . There was no significant change in the diagnostic accuracy between the study groups and between the physician groups . All patients requiring laparotomy were identified and no significant complication was noted in the morphine group . CONCLUSIONS Intravenous morphine provides significant pain reduction to children with acute abdominal pain without adversely affecting the examination , and morphine does not affect the ability to identify children with surgical conditions Aim : To see whether laparoscopy improves the accuracy of a clinical diagnosis of acute appendicitis in women of reproductive age , and to determine what the long-term sequelae are of not removing an appendix deemed at laparoscopy to be normal . Method : The initial part of the study was undertaken during 1991–1992 . Female patients between 16 and 45 years were eligible for inclusion once a clinical decision had been made to perform an appendicectomy for suspected acute appendicitis . Following consent , patients were r and omized into two groups . One group had open appendicectomy , as planned . The other group had laparoscopy , followed by open appendicectomy only if the appendix was seen to be inflamed or was not visualized . The end points for the study were the clinical outcomes of all patients , and the results of histology , where appropriate . An attempt was made to contact all patients at 10 years to determine whether they had had a subsequent appendicectomy , or had been diagnosed with another abdominal condition that might be relevant to the initial presentation in 1991–1992 . Results : Laparoscopic assessment was correct in all cases in which the appendix was visualized . Diagnostic accuracy was improved from 75 % to 97 % . Laparoscopy was associated with no added complications , no increase in hospital stay in patients who went on to appendicectomy , and a reduction in hospital stay for those who underwent laparoscopy alone . No patients developed a problem over the 10-year follow-up period from having a normal-looking appendix not removed at laparoscopy . Conclusion : Laparoscopic assessment of the appendix is reliable , and to leave a normal-looking appendix at laparoscopy does not appear to cause any long-term problems OBJECTIVES The total white blood cell ( WBC ) count and temperature are often expected to be elevated in patients with appendicitis . Clinicians often use the results of these parameters in making a judgment about the presence or absence of disease . The objective of this study was to assess the discriminatory value of the total WBC count and presenting body temperature in patients presenting to the emergency department ( ED ) with signs and symptoms suggestive of appendicitis . METHODS This was a prospect i ve consecutive case series in a university ED with an annual census of 38,000 . All patients presenting to the ED in whom the diagnosis of appendicitis was the attending physician 's primary consideration were enrolled . Measures included age , gender , symptoms , physical findings , patient temperature as taken in the ED , initial total WBC count , and discharge diagnosis . Admitted patients were followed up until surgical or clinical outcomes , and discharged patients were followed up by telephone two weeks after the initial visit . All statistical analysis was performed using StatsDirect version 1.9.8 . RESULTS A total of 293 patients were enrolled over a two-year study period . The total WBC count was measured in 274 cases , and the temperature was measured in 293 cases . There were 130 male patients and 163 female patients . The mean age of the patients was 30.8 years ( range , 7 - 75 years ) . Appendicitis was confirmed in 92 patients . In this study group of patients , a total WBC count > 10,000 cells/mm(3 ) had a sensitivity of 76 % ( 95 % confidence interval [ 95 % CI ] = 65 % to 84 % ) and a specificity of 52 % ( 95 % CI = 45 % to 60 % ) . The positive predictive value ( PPV ) was 42 % ( 95 % CI = 35 % to 51 % ) , and the negative predictive value ( NPV ) was 82 % ( 95 % CI = 74 % to 89 % ) . The positive likelihood ratio ( LR ) was 1.59 ( 95 % CI = 1.31 to 1.93 ) , and the negative LR was 0.46 ( 95 % CI = 0.31 to 0.67 ) . A temperature > 99.0 degrees F had a sensitivity of 47 % ( 95 % CI = 36 % to 57 % ) and a specificity of 64 % ( 95 % CI = 57 % to 71 % ) . The PPV was 37 % ( 95 % CI = 29 % to 46 % ) , and the NPV was 72 % ( 95 % CI = 65 % to 79 % ) . The positive LR was 1.3 ( 95 % CI = 0.97 to 1.72 ) , and the negative LR was 0.82 ( 95 % CI = 0.65 to 1.01 ) . The areas under the curve for the receiver-operating characteristic ( ROC ) curve were 0.72 ( 95 % CI = 0.65 to 0.79 ) and 0.59 ( 95 % CI = 0.52 to 0.66 ) for an elevated total WBC count and an elevated temperature , respectively . CONCLUSIONS An elevated total WBC count > 10,000 cells/mm(3 ) , while statistically associated with the presence of appendicitis , had very poor sensitivity and specificity and almost no clinical utility . There was minimal statistical association between a temperature of > 99 degrees F and the presence of appendicitis . The ROC curve suggests there is no value of total WBC count or temperature that has sufficient sensitivity and specificity to be of clinical value in the diagnosis of appendicitis . Clinicians should be wary of reliance on either elevated temperature or total WBC count as an indicator of the presence of appendicitis HYPOTHESIS Ultrasonography can be efficiently performed using new criteria for the diagnosis of acute appendicitis . DESIGN Prospect i ve trial . PATIENTS Eighty-nine patients admitted to the hospital with suspected appendicitis between March 1998 and November 2000 . INTERVENTION At hospital admission , a staff surgeon evaluated each patient and determined whether the patient had appendicitis requiring immediate surgery or another disease . Patients then underwent ultrasonography . A sonographic transducer was placed on the area of maximal tenderness . When the pathological manifestation was depicted , the examiner slipped a fingertip between the transducer and the patient 's skin and then pressed the area of depicted pathological manifestation to find pinpoint tenderness . When maximal pinpoint tenderness was noted on the appendix or on pathological manifestations contiguous to the appendix , we diagnosed the condition as appendicitis . MAIN OUTCOME MEASURES Sensitivity , specificity , positive and negative predictive values , and overall accuracy . RESULTS The diagnosis of appendicitis by this criteria had a sensitivity of 86.7 % , a specificity of 89.7 % , a positive predictive value of 94.5 % , a negative predictive value of 76.5 % , and overall accuracy of 87.6 % . All 50 patients with pinpoint tenderness noted on the appendix had appendicitis . The surgeon 's initial clinical impression had a sensitivity of 83.3 % , a specificity of 44.8 % , a positive predictive value of 75.8 % , a negative predictive value of 56.5 % , and overall accuracy of 70.8 % . CONCLUSIONS The efficacy of ultrasonography using the simple criteria was superior to that of the surgeon 's initial clinical impression ( P<.001 ) . Our ultrasonographic criteria for the diagnosis of appendicitis are simple to use and efficient The objective of this study was to examine current practice patterns of analgesia administration among emergency physicians ( EPs ) when caring for a patient with an acute abdomen . Cross sectional data were acquired by a survey mailed in October 1997 to 1,000 American College of Emergency Physicians ( ACEP ) members from a purchased ACEP mailing list which contained 1,000 r and omized ACEP members . A repeat survey was sent to nonresponders 2 months later and a r and om subset of recurrent nonresponders were telephoned . The question naire focused on physician demographics , practice patterns , and factors which influenced physician decision of when and whether to administer pain medication , specifically opiates , to patients with an acute abdomen . Forty-four percent of surveys were returned . Seventy-seven percent of respondents were men with an average of 10 years of experience . Fifty-seven percent were residency trained in emergency medicine . Although eighty-five percent felt that the conservative administration of pain medication did not change important physical findings on the physical examination , 76 % choose not to give an opiate analgesic until after the examination by a surgeon . Twenty-five percent of patients did not receive any pain medication in the department . In conclusion , although EPs report that the judicious administration of pain medication does not mask important examination findings , the majority wait until after the surgeon has evaluated the patient to deliver analgesics Abstract Objectives : To evaluate the impact of early abdominopelvic computed tomography in patients with acute abdominal pain of unknown cause on length of hospital stay and accuracy of diagnosis . Design : R and omised , prospect i ve controlled trial . Setting : Teaching hospital in Engl and . Participants : 120 patients admitted with acute abdominal pain for which no immediate surgical intervention or computed tomography was indicated . Intervention : 55 participants were prospect ively r and omised to early computed tomography ( within 24 hours of admission ) and 65 to st and ard practice ( radiological investigations as indicated ) . Main outcome measures : Length of hospital stay , accuracy of diagnosis , and , owing to a possible effect on inpatient mortality , deaths during the study . Results : Early computed tomography reduced the length of hospital stay by 1.1 days ( geometric mean 5.3 days ( range 1 to 31 ) v 6.4 days ( 1 to 60 ) ) , but the difference was non-significant ( 95 % confidence interval , 8 % shorter stay to 56 % longer stay , P=0.17 ) . Early computed tomography missed significantly fewer serious diagnoses . Seven in patients in the st and ard practice arm died . Only 50 % ( 59 of 118 ) of diagnoses on admission were correct at follow up at 6 months , but this improved to 76 % ( 90 ) of diagnoses after 24 hours . Conclusions : Early abdominopelvic computed tomography for acute abdominal pain may reduce mortality and length of hospital stay . It can also identify unforeseen conditions and potentially serious complications . What is already known on this topic Computed tomography improves the accuracy of diagnosis of several acute abdominal conditions Uncontrolled studies have shown improvements in accuracy of diagnosis after computed tomography ; none have described an effect on mortality What this study adds Early abdominopelvic computed tomography for acute abdominal pain can identify unforeseen serious abdominal conditions It may also reduce length of hospital stay and might reduce inpatient BACKGROUND The accuracy of the clinical diagnosis of acute appendicitis in patients more than 50 years old was studied in connection with the Research Committee of the World Organization of Gastroenterology ( OMGE ) survey of acute abdominal pain . Criteria for inclusion and the diagnostic criteria in this prospect i ve study were those set out by the OMGE Research Committee . METHODS The clinical findings in each patient were recorded in detail , using a predefined structured data collection sheet , and the collected data were compared with the final diagnosis of the patients . Twenty-three preoperative clinical history variables , 14 clinical signs , and 3 tests were evaluated in a single variable and multivariate analysis . RESULTS In multivariate logistic regression analysis the most significant predictors of acute appendicitis in patients more than 50 years old were tenderness ( relative risk ( RR ) = 39.4 ) , rigidity ( RR = 18.8 ) , and pain at diagnosis ( RR = 11.0 ) . The sensitivity of the preoperative clinical decision is detecting acute appendicitis in the aged was 0.87 , with a specificity of 0.92 , an efficiency of 0.91 and a usefulness index ( UI ) of 0.69 . The computer-aided diagnostic score ( DS ) reached a sensitivity of 0.92 in detecting acute appendicitis , with a specificity of 0.90 and an efficiency of 0.90 . When the patients with a DS value between -0.47 and 0.07 were considered nondefined ( n = 43 , follow-up required before the decision to operate ) , the efficiency of the computer-aided diagnosis in detecting acute appendicitis in the aged improved to 0.97 . In patients more than 50 years old whose body temperature was available ( n = 374 ) , tenderness , rigidity , location of pain at diagnosis , and body temperature predicted significantly acute appendicitis . At a cut-off level of -1.49 the diagnostic score reached a sensitivity of 0.94 in detecting acute appendicitis , with a specificity of 0.91 , an efficiency of 0.92 and a UI of 0.80 . When the patients with a DS value between -1.49 and 0.46 were considered nondefined ( n = 43 , follow-up required before the decision to operate ) , the sensitivity of the computer-aided diagnosis in detecting acute appendicitis in the aged was 0.92 , with a specificity of 0.99 and an efficiency of 0.98 , and the UI improved to 0.84 . CONCLUSION Acute abdominal pain at the right lower quadrant , with tenderness , rigidity , and increased body temperature ( > or = 37.1 degrees C ) , is indicative of acute appendicitis in patients more than 50 years old . The diagnostic scoring system did perform well , increasing the sensitivity , specificity , efficiency , and usefulness index of the diagnosis of acute appendicitis in the aged OBJECTIVE To determine whether morphine affects evaluation or outcome for patients with acute abdominal pain . METHODS Prospect i ve , double-blind , placebo-controlled administration of morphine sulfate ( MS ) or normal saline ( NS ) in the setting of acute abdominal pain . The study was performed at a military ED with an annual census of 60,000 visits . Patients > or = 18 years old who had abdominal pain for < or = 48 hours were included . Patients who were allergic to MS or who had systolic blood pressures < 90 mm Hg were excluded . The physicians indicated a provisional diagnosis , a differential diagnosis , and a provisional disposition . Study solution was titrated to the patient 's assessment of adequate analgesia ( up to a volume equivalent of 20 mg of MS ) ; pain response was monitored using a visual analog scale ( VAS ) . The patients were followed until diagnosis occurred or symptoms resolved . RESULTS Of 75 patients enrolled , 71 completed the study ; 35 patients received MS and 36 received NS . More than half ( 44 ; 62 % ) of the patients were admitted from the ED ; 28 patients underwent surgery . The VAS pain level improved more for the MS group , 3.9 + /- 2.8 cm , than it did for the NS group , 0.8 + /- 1.5 cm ( p < 0.01 ) . Study solution dose was less in the MS group than it was in the NS group , 1.5 + /- 0.5 mL vs 1.8 + /- 0.4 mL ( p < 0.01 ) . There was no difference between the groups when comparing accuracy of provisional or differential diagnosis with that of final diagnosis . Differences between provisional and actual dispositions were the same in all groups . There were 3 diagnostic or management errors in each group . CONCLUSIONS When compared with saline placebo , the administration of MS to patients with acute abdominal pain effectively relieved pain and did not alter the ability of physicians to accurately evaluate and treat patients HYPOTHESIS Focused helical computed tomographic ( CT ) scanning with rectal contrast only is a superior diagnostic modality compared with the traditional triple-contrast CT scan for the diagnosis of acute appendicitis . DESIGN Prospect i ve r and omized analysis of both CT scan modalities . INTERVENTIONS Only patients with uncertain diagnosis of acute appendicitis were entered in the study . The patients were then r and omized to undergo the traditional triple-contrast CT scan or the new focused CT scan with rectal contrast only . Surgical management included operation or observation for 23 hours . RESULTS Ninety-one patients participated in the study , including 52 in the triple-contrast group and 39 in the rectal-contrast group . The demographics of the triple-contrast vs the rectal-contrast groups were similar . The triple-contrast group had a sensitivity of 97 % , specificity of 86 % , positive predictive value of 90 % , and negative predictive value of 93 % . The rectal-contrast group had a sensitivity of 88 % , specificity of 100 % , positive predictive value of 100 % , and negative predictive value of 100 % . There were 4 false-positive findings and 1 false-negative finding in the triple-contrast group compared with none in the rectal-contrast group . In the triple-contrast group , there were 13 perforated appendixes compared with 1 in the rectal-contrast group . The cost of a triple-contrast scan was 620 US dollars compared with 305 US dollars for a focused rectal-contrast scan . The negative appendectomy rate for the study was 8.0 % ( 4 of 48 patients in the triple-contrast group vs 3 of 39 in the rectal-contrast group ) . CONCLUSIONS The demographics , sensitivity , specificity , and positive and negative predictive values were comparable in both groups . The focused rectal-contrast procedure was better tolerated by patients and demonstrated decreased morbidity , delay to diagnosis , perforation rate , and negative appendectomy rate with no missed diagnosis and decreased cost . Therefore , we believe that focused helical CT scanning with rectal contrast only is a superior diagnostic modality compared with the traditional triple-contrast CT scan for the diagnosis of acute appendicitis OBJECTIVE To evaluate the influence of white cell count ( WCC ) on the decision to operate on patients with right lower abdominal pain . DESIGN Open study . SETTING University hospital , Switzerl and . SUBJECTS 221 adult patients admitted to emergency department with right lower abdominal pain . INTERVENTIONS Surgeons were unaware of the WCC until after they had initially decided whether to remove the appendix . They were told the result and asked if it would influence their final decision . MAIN OUTCOME MEASURE Whether surgeons changed their minds about operation when told the initial WCC . RESULTS 112 Patients ( 51 men and 61 women ) were operated on , of which 44 men ( 52 % ) and 42 women ( 31 % ) had histologically confirmed appendicitis . The decision to operate was influenced by the initial WCC in only 6 patients ( 3 % , 95 % confidence interval ( CI ) 0.6 to 4.9 % ) . At follow up after 30 days the change of decision in the 6 patients had been correct in 5 . CONCLUSION The WCC did not significantly influence surgical decision-making in the group of patients who were suspected of having acute appendicitis BACKGROUND The objective of this study was to determine if routine use of computed tomography ( CT ) for the diagnosis of appendicitis is warranted . METHODS During a one-year study period , all patients who presented to the surgical service with possible appendicitis were studied . One hundred eighty-two patients with possible appendicitis were r and omized to clinical assessment ( CA ) alone , or clinical evaluation and abdominal/pelvic CT . A true-positive case result ed in a laparotomy that revealed a lesion requiring operation . A true-negative case did not require operation at one-week follow-up evaluation . Hospital length of stay , hospital charges , perforation rates , and times to operation were recorded . RESULTS The age and gender distributions were similar in both groups . Accuracy was 90 % in the CA group and 92 % for CT . Sensitivity was 100 % for the CA group and 91 % for the CT group . Specificity was 73 % for CA and 93 % for CT . There were no statistically significant differences in hospital length of stay ( CA = 2.4 + /- 3.2 days vs. CT = 2.2 + /- 2.2 days , p = 0.55 ) , hospital charges ( CA = 10,728 US dollars + /- 10,608 vs. CT = 10,317 US dollars + /- 7,173 , p = 0.73 ) or perforation rates ( CA = 6 % vs. CT = 9 % , p = 0.4 ) . Time to the operating room was shorter in the CA group , 10.6 + /- 8.4 h vs. CT , 19.0 + /- 19.0 h ( p < 0.01 ) . CONCLUSIONS Clinical assessment unaided by CT reliably identifies patients who need operation for acute appendicitis , and they undergo surgery sooner . Routine use of abdominal/pelvic CT is not warranted . Further research is needed to identify sub-groups of patients who may benefit from CT . Computed tomography should not be considered the st and ard of care for the diagnosis of appendicitis Whereas controversy surrounds emergency department ( ED ) analgesia administration to patients with undifferentiated abdominal pain , few studies have addressed the level of patient-physician agreement on abdominal pain severity and need for opioid analgesia . This prospect i ve study was undertaken to assess concordance between emergency physicians and patients on abdominal pain severity . Study subjects were a convenience sample of 30 adults seen in an urban university-affiliated tertiary care ED ( annual census 65,000 ) who had undifferentiated abdominal pain meeting an initial severity threshold of 5 on a 10 cm visual analog scale ( VAS ) marked by the patient . Patients ' and physicians ' VAS scores , obtained in blinded fashion at presentation ( t0 ) and at one ( t1 ) and two ( t2 ) hours into the ED stay , were compared with t test ( VAS scores ) and sign-rank ( percent change in VAS scores ) analyses . In addition , patients and physicians were asked at each assessment time , in blinded fashion , " Is the pain severe enough to warrant morphine ? " The kappa statistic was used to characterize the degree of agreement between physician and patient assessment s as to whether opioids were indicated . At t0 , t1 , and t2 , patients ' mean VAS scores ( 7.5 , 6.7 , and 5.1 ) were significantly ( P < .05 ) higher than the corresponding physicians ' VAS scores ( 5.3 , 4.7 , and 3.9 ) . Though VAS scores for physicians started lower than those of patients , the percentage changes in scores from one assessment to the next were similar by Wilcoxon sign-rank testing ( P > .50 for time intervals t0 - t1 and t1 - t2 ) . Overall , patients and physicians agreed on the question of whether pain was sufficient to warrant opioids in 71 of 90 ( 78.9 % ) assessment s ; the corresponding kappa statistic of .57 indicated moderate agreement ( P < .0001 ) . These results , indicating that patients and physicians usually agree on whether opioids are warranted for abdominal pain , have important implication s for further research on ED analgesia in this population Giving an analgesic to patients with right lower quadrant ( RLQ ) pain causes greater alteration of abdominal signs predictive of appendicitis than placebo . A r and omized double-blinded controlled trial of 68 patients who received either tramadol or placebo . Absence or presence of seven abdominal signs ( tenderness on light and deep palpation , tenderness in the RLQ and elsewhere , rebound , cough , and percussion tenderness ) and pain ( 100 mm Visual Analog Scale [ VAS ] ) at 0 and 30 minutes were recorded . The predictive value of each physical finding ( PF ) was measured using an 11-point PF score weighted by likelihood ratios . There was significant reduction in mean VAS of 14.2 mm ( 95 % CI 5.6 to 22.8 ) in analgesic group versus 6.5 mm ( 95 % CI 1.6 to 11.4 ) in placebo group . The analgesic group had less normalization of signs as measured by the PF score in all patients [ 32 of 154 ( 20.8 % ) versus 40 of 121 ( 33.1 % ) ( P = .031 ) ] and in those with proven appendicitis [ 4 of 33 ( 12.1 % ) versus 10/22 ( 45.5 % ) ( P = .014 ) ] . Parenteral use of tramadol in emergency department patients with RLQ pain result ed in significant levels of pain reduction without concurrent normalisation of abdominal examination findings indicative of acute appendicitis The diagnosis of acute appendicitis is usually made from the history and physical examination . Recently , abdominal ultrasonography ( US ) , laparoscopy , computerized tomography ( CT ) , and barium enema ( BE ) have been used in the preoperative evaluation of patients with presumed appendicitis in order to improve the diagnostic accuracy . However , the usefulness of these tests in verifying the diagnosis of appendicitis has not been established . We review ed the medical records of 203 patients who underwent appendectomy . One hundred patients were surgically treated before 1984 ( group I ) and 103 patients underwent surgery after 1988 ( group II ) . Patients in group II were more likely to have preoperative US , laparoscopy , CT , or BE ( 24 in group II versus 3 in group I , p < 0.05 ) . When groups I and II were compared , the rates of perforation ( 27 % versus 20 % ) , normal appendectomy ( 8 % versus 11 % ) , and the interval between admission and operation ( 12.2 hours versus 10.7 hours ) and length of hospitalization ( 5.0 days versus 5.1 days ) were not significantly different . We concluded that although adjunctive testing may be beneficial in selected patients , its routine use in patients suspected of having appendicitis can not be advocated at present This was conducted to evaluate the analgesic effect of intravenous tenoxicam ( non-steroidal anti-inflammatory drug ) in the treatment of biliary colic pain and compared with spasmolytics . Thirtytwo patients ( 26 women , 6 men , mean age 47 , range 38 - 55 years ) with acute biliary colic were entered for study . They were allocated r and omly to receive either tenoxicam 20 mg i.v . or hyoscine N-butylbromide 20 mg i.v . The patients recorded their pain severity on 5 point scale . The results showed that tenoxicam caused significant pain relief in 10 out of 16 patients at 30 min ( mean pain score decreased from 2.75 + /- 0.93 to 0.49 + /- 0.51 , p < 0.05 ) and in other 4 patients at 60 min ( mean pain score decreased to 0.58 + 5.7 , p < 0.05 ) . None of these patients developed acute cholecystitis or pain relapse over a period of 24 h follow up . With use of hyoscine N-butylbromide , 7 out 16 patients had significant pain relief at 30 min ( mean pain score decreased from 2.62 + /- 1.01 to 0.57 + /- 0.53 , p < 0.05 ) and 3 other patients relieved at 60 min ( mean pain score decreased to 0.66 + /- 0.57 , p < 0.05 ) . Four patients showed pain relapse within 24 h and needed pethidine-rescue treatment , two of them developed acute cholecystitis . Three out of 6 patients who showed no response to hyoscine N-butylbropmide and treated with 100 mg pethidine progressed to acute cholecystitis . We concluded that intravenous tenoxicam has rapid and prolong analgesic effects in the treatment of acute biliary colic as compared to hyoscine N-butylbroimde and it prevents the progression to acute cholecystitis PURPOSE To determine the influence of early pain relief on the diagnostic performance of ultrasonography ( US ) and on the appropriateness of the surgical decision . MATERIAL S AND METHODS A prospect i ve r and omized , double-blind placebo-controlled trial with morphine was conducted . A visual analog scale was used to evaluate pain in 340 patients aged 16 years or older . US was performed with a st and ardized protocol . Diagnosis was confirmed at histologic analysis or , in the patients released without surgery , at follow-up . RESULTS One hundred seventy-five patients were injected with morphine , and 165 were injected with the placebo . Pain relief was stronger in the morphine group . In the morphine group , US had lower ( 71.1 % ) sensitivity ( difference , -9.5 % ; 95 % CI , -18.5 % , -0.5 % ) and higher ( 65.2 % ) specificity ( difference , 11.4 % ; 95 % CI , 1.0 % , 21.8 % ) . This group had also a higher positive predictive value ( 64.6 % ) and a lower negative predictive value ( 71.4 % ) , but the differences between this group and the placebo group were not statistically significant . Among female patients , the decision to operate was appropriate more often in the morphine group ( 75.8 % ) , but the difference between this group and the placebo group was not statistically significant ( 5.1 % ; 95 % CI , -7.4 % , 17.6 % ) . In male patients and overall , opiate analgesia did not influence the appropriateness of the decision . The appropriateness to discharge patients without surgery was 100 % in all groups . CONCLUSION Morphine does not improve US-based diagnosis of appendicitis BACKGROUND & AIMS Our aim was to investigate whether diagnostic imaging is required if the clinical presentation suggests acute appendicitis with high probability . METHODS On the basis of clinical findings , 350 consecutive patients with clinical suspicion of acute appendicitis were prospect ively divided into 3 groups as follows : low , intermediate , and high probability of having appendicitis . All patients then underwent diagnostic ultrasonography . The clinical likelihood of appendicitis and the ultrasonographic results were correlated with the definite diagnoses . RESULTS In the patients with clinical ly low probability of having appendicitis , appendicitis was present in 10 % ( 11 of 109 patients ) , and , in those with intermediate probability , appendicitis was present in 24 % ( 23 of 97 patients ) . Patients with clinical ly high probability of having appendicitis had appendicitis in 65 % ( 94 of 144 patients ) , an alternative diagnosis in 18 % ( 26 of 144 patients ) , and no specific definitive diagnosis in 17 % ( 24 of 144 patients ) . Ultrasonography diagnosed appendicitis and the differential diagnoses with a sensitivity of 98 % and 97 % , specificity of 98 % and 100 % , positive predictive value of 96 % and 99 % , negative predictive values of 99 % and 99 % , and accuracy of 98 % and 99 % , respectively . CONCLUSIONS Even in patients with clinical ly high probability of acute appendicitis , diagnostic imaging should be performed because it accurately depicts a high percentage of normal appendices and differential diagnoses OBJECTIVE To identify systematic errors in surgeons ' estimations of the importance of diagnostic variables in the decision to explore patients with suspected appendicitis . DESIGN Prospect i ve case series . SETTING Two emergency departments , Sweden . PATIENTS 496 patients with suspected appendicitis on admission , of whom 194 had a correct operation for appendicitis and 59 had a negative exploration . MAIN OUTCOME MEASURES Predictors of a negative exploration expressed as the odds ratio ( OR ) for negative exploration . Variables influence on the decision to operate , expressed as the OR for operation , compared with the true diagnostic importance , expressed as the OR for appendicitis . RESULTS Predictors of negative explorations were high ratings in variables describing pain and tenderness ( patient 's perceived pain , abdominal tenderness , rebound tenderness , guarding or rectal tenderness ) , weak or absent inflammatory response , female sex , long duration of symptoms and absence of vomiting , with OR of 1.8 - 3.0 . Pain and tenderness had too strong an influence on the decision to operate whereas the lack of an inflammatory response , no vomiting , and long duration of symptoms were not given enough attention . There was no sex difference in the proportion of patients with non-surgical abdominal pain ( NSAP ) who were operated on , but NSAP was more common and appendicitis less common among women , leading to a larger proportion of negative appendicectomies among women . CONCLUSION Negative explorations in patients with suspected appendicitis are related to systematic errors in the clinical diagnosis with too strong an emphasis on pain and tenderness , and too little attention paid to duration of symptoms and objective signs of inflammation . Rectal tenderness is not a sign of appendicitis . The risk of diagnostic errors is similar in men and women This is a prospect i ve study on 123 r and omly selected patients admitted with the diagnosis of acute appendicitis . The value of rebound tenderness as a clinical diagnostic tool was statistically compared to those of some other physical signs ; namely guarding , rigidity and Rovsing 's sign . Rebound tenderness was found to carry the highest sensitivity ( 94.7 % ) , negative predictive value ( 81.3 % ) , reliability ( 49.1 % ) , and association with histological diagnosis ( P < 0.05 ) . However , its specificity and positive predictive value was not significantly different from those of other physical signs . It is concluded that , in contradistinction to some previously published reports , our study emphasizes the role of rebound tenderness in the clinical diagnosis of acute appendicitis Analgesics in patients with acute abdominal pain are often withheld for fear that they may change physical examination findings and thus may be unsafe . We conducted a r and omized , prospect i ve , placebo-controlled trial to investigate changes in physical examination following the administration of placebo , 5 mg , or 10 mg of morphine to 49 patients with acute abdominal pain . One patient was withdrawn secondary to inadequate documentation . Of the 48 patients who completed the trial , a statistically significant change in physical examination was noted in both groups receiving analgesics , but not in the placebo group . No adverse events or delays in diagnosis were attributed to the administration of analgesics . We conclude that physical examination does change after the administration of analgesics in patients with acute abdominal pain and that a larger study is needed to evaluate analgesic safety in this sub population of emergency department patients UNLABELLED To the authors ' knowledge , no outcome -based , r and omized clinical trial of the safety of opioid analgesics in acute abdominal pain exists . OBJECTIVES 1 ) To assess the feasibility of a r and omized clinical trial of opioid safety by estimating the adverse outcome rate among patients with abdominal pain severe enough to necessitate opioid analgesics . 2 ) To explore the association of opioid administration with adverse outcomes in acute abdominal pain . METHODS The authors conducted a prospect i ve observational study of emergency department ( ED ) abdominal pain patients , and followed them by telephone at three weeks to determine whether an adverse outcome occurred ( defined as obstruction , perforation , ischemia , hemorrhage , peritonitis , sepsis , or death ) . A logistic regression of factors predicting adverse outcome was performed . RESULTS Adverse outcomes occurred in 67 of 860 abdominal pain patients ( 7.8 % , 95 % CI = 6.1 % to 9.8 % ) , and 252 of 860 ( 29 % ) received opioids . The adverse outcome rate was 12.7 % ( 95 % CI = 9.0 % to 17.0 % ) among patients who received opioids . Variables predictive of adverse outcome in logistic regression included : ED diagnosis of adverse outcome ( OR 12.4 ) , age ( OR 1.6 per decade ) , fever ( OR 4.6 ) , received opioids ( OR 2.1 ) , pain duration ( OR 1.5 per day ) , and leukocytosis ( OR 2.0 ) . CONCLUSIONS A clinical trial would need to r and omize more than 1,500 patients to establish the equivalent adverse outcome rates of opioids and placebo : the sample size of all existing studies combined is insufficient to make such a conclusion . Although opioids were associated with a higher adverse outcome rate in this logistic regression , the authors believe this may be due to confounding by pain severity . They emphasize that the study 's design precludes conclusion of a causal link . No change in clinical practice is warranted . A r and omized clinical trial of sufficient size to definitively resolve this issue is needed Background and aims : This study compared two histopathological examinations for the diagnosis of neurogenic appendicopathy ( NA ) , assessed the frequency of NA , and evaluated whether it is a clinical disease entity distinct from acute appendicitis . Patients and methods : In a prospect i ve observational multicenter study ( surgical departments of five hospitals with one reference pathology ) we evaluated 282 patients who underwent appendectomy for suspected appendicitis ; we examined the frequency of NA in acute appendicitis and in the negative appendectomy group . For the diagnosis two staining methods were compared . We also attempted to determine clinical features of NA . Results : We observed 93 % accuracy for hematoxylin-eosin staining compared with S-100 staining ( reference st and ard ) in the diagnosis of NA . There was NA in 3.8 % of patients with acute appendicitis and in 47 % of those with negative appendectomy . We observed significant differences between the three groups ( NA without appendicitis , acute appendicitis , and negative appendectomy without neurogenic appendicopathy ) only for sex , age , vomiting , similar previous complaints , rebound tenderness , guarding , rigidity , leukocytes ( univariate analysis ) and sex ( multivariate analysis ) . Conclusion : Neurogenic appendicopathy is a histopathological entity that can be identified by hematoxylin-eosin staining . History and clinical examination do not enable us preoperatively to differentiate between acute appendicitis , NA , and negative appendectomy OBJECTIVE To assess the role of 5-Hydroxy Indole Acetic Acid ( 5-HIAA ) levels in spot urine in diagnosis of acute appendicitis . DESIGN A prospect i ve , controlled study . SETTING Ankara Numune Teaching and Research Hospital , Ankara , Turkey . SUBJECT Twenty six patients with histologically proven acute appendicitis following appendectomy were included in the study . Control group with consisted of patients prepared for hernia repair in the same duration . In the preoperative period , urine sample s were collected from every patient for measurement of 5-HIAA . RESULTS The study group comprised 26 patients ; 15 of those had high urine 5-HIAA levels , whereas 11 patients had values within normal range . None of ten control patients displayed positive test result . The test had 58 % sensitivity and 48 % specificity . In histopathological examination only two of ten patients with gangrenous appendicitis showed positive test result , whereas 13 of 16 patients with no histopathological gangrenous changes had high values . CONCLUSION Urine 5-HIAA measurement has low sensitivity and specificity . The value of the test is even clearly lower in gangrenous appendicitis . This may be misleading in management of patients in late phase of appendicitis and in cases with perforation which is mainly responsible for morbidity The objective of this study was to determine if judicious dosing of morphine sulfate can provide pain relief without changing important physical examination findings in patients with acute appendicitis . We conducted a prospect i ve , r and omized , double-blind crossover design . Patients scheduled for appendectomy were r and omized to two groups . Group A received 0.075 mg/kg intravenous morphine sulfate and 30 minutes later received placebo . The sequence of medication was reversed in group B. Patients were examined by a surgical resident and an EM attending before and after receiving medication . Six explicit physical examination findings were documented as absent , indeterminate , or present . Physicians were also asked if they felt overall examination findings had changed after medication . Patient 's visual analog scale ( VAS ) was recorded before each medication and at study completion . Thirty-four patients were enrolled and full data were available for 22 patients . Neither morphine nor placebo caused a significant change in individual examination findings . Three patients in both groups were judged to have a change in their examination after medication . The median change in VAS was 20 mm after morphine and 0 mm after placebo ( P = .01 ) . In this pilot study , patients with clinical signs of appendicitis were treated with morphine and had significant improvement of their pain without changes in their physical examination BACKGROUND Because of concerns about masking important physical findings , there is controversy surrounding whether it is safe to provide analgesia to patients with undifferentiated abdominal pain . The purpose of this study was to address the effects of analgesia on the physical examination and diagnostic accuracy for patients with abdominal pain . STUDY DESIGN The study was a prospect i ve , double-blind clinical trial in which adult Emergency Department ( ED ) patients with undifferentiated abdominal pain were r and omized to receive placebo ( control group , n = 36 ) or morphine sulphate ( MS group , n = 38 ) . Diagnostic and physical examination assessment s were recorded before and after a 60-minute period during which study medication was titrated . Diagnostic accuracy and physical examination changes were compared between groups using univariate statistical analyses . RESULTS There were no differences between control and MS groups with respect to changes in physical or diagnostic accuracy . The overall likelihood of change in severity of tenderness was similar in MS ( 37.7 % ) as compared with control ( 35.3 % ) patients ( risk ratio [ RR ] 1.07 , 95 % confidence interval [ CI ] 0.64 - 1.78 ) . MS patients were no more likely than controls to have a change in pain location ( 34.0 % versus 41.2 % , RR 0.82 , 95 % CI 0.50 - 1.36 ) . Diagnostic accuracy did not differ between MS and control groups ( 64.2 % versus 66.7 % , RR 0.96 , 95 % CI 0.73 - 1.27 ) . There were no differences between groups with respect to likelihood of any change occurring in the diagnostic list ( 37.7 % versus 31.4 % , RR 1.20 , 95 % CI 0.71 - 2.05 ) . Correlation with clinical course and final diagnosis revealed no instance of masking of physical examination findings . CONCLUSIONS Results of this study support a practice of early provision of analgesia to patients with undifferentiated abdominal pain The objective of the study was to assess the validity and reliability of the visual analog scale ( VAS ) in the measurement of acute abdominal pain , and to identify the minimum clinical ly significant difference in VAS scores among patients with acute abdominal pain . The study was undertaken in preparation for a r and omized clinical trial of opioid use in acute abdominal pain . A prospect i ve , observational cohort study of a convenience sample of patients presenting to 2 urban EDs with the chief complaint of acute abdominal pain was conducted . At time 0 and 1 minute later each subject indicated pain severity on a 100 mm VAS . This was repeated every 30 minutes for 2 hours . Patients were also asked to contrast their current pain severity with their pain in the preceding 30 minutes using one of 5 grade d verbal descriptors : " much less pain , " " little less pain , " " the same pain , " " little more pain , " and " much more pain . " Validity was assessed by performing an analysis of variance for linear trend on the association between the 5 categorical pain descriptors and change in VAS scores . Reliability was assessed using the intra-class correlation coefficient ( ICC ) between VAS scores taken 1 minute apart , supplemented by a Bl and -Altman analysis . The minimum clinical ly significant difference in pain was defined as the mean difference between sequential VAS scores obtained 30 minutes apart when the patient noted a " little less " or " little more " pain . Differences in VAS scores increased linearly as pain descriptors escalated from " much less " to " much more " pain ( P < .001 ) . Reliability was high , ICC = 0.99 [ 95%CI 0.989 to 0.992 ] for 0 and 1 minute VAS scores . The minimum clinical ly significant difference in acute abdominal pain was 16 mm ( 95 % CI 13 , 18 mm ) . VAS measures of acute abdominal pain are valid and reliable . The 95 % CI surrounding the minimum clinical ly significant difference of approximately 16 mm overlaps with the 95 % CI of minimum clinical ly significant difference of approximately 13 mm reported previously in traumatic and other types of acute pain . We conclude that the VAS is a method ologically sound instrument for quantitative assessment of acute abdominal pain and for detecting clinical ly important changes in such pain OBJECTIVES To compare the accuracy of laparoscopy performed within 24 h of admission and the conventional method based on clinical observation in the etiological diagnosis of non-specific acute lower abdominal pain ( NSLAP ) in women of reproductive age . METHODS A total of 110 patients who met the selection criteria and were seen from November 1997 to June 2000 at the Instituto Materno Infantil , a referral hospital for maternal and perinatal care in Bogotá , were r and omly divided into two groups . The effectiveness of each method was evaluated according to number of diagnoses reached , length of in-patient stay before diagnosis , complications , and diagnostic accuracy when compared with a st and ard given by microbiological and histopathological findings as well as clinical course . RESULTS The early laparoscopy group did not experience more accurate diagnoses ( 85 % vs. 79 % , P=0.61 ) or a greater number of complications ( 11 % vs. 9 % , P=0.48 ) , although the patients ' stay was shorter ( 1.3 vs. 2.3 days , P=0.008 ) than the stay of the conventional-diagnosis group . Sensitivity analysis showed more accurate judgements with laparoscopy in four of the five NSLAP causes , but only in two of the cases did this greater accuracy have clinical significance . CONCLUSIONS Early laparoscopy did not show a clear benefit in women with NSLAP Abdominal pain of uncertain aetiology ( non‐specific abdominal pain ; NSAP ) is the commonest reason for emergency surgical admission . The aim of this study was to examine the role of early laparoscopy in the management of NSAP |
1,290 | 15,846,610 | There was no evidence that group therapy was more effective than a similar intensity of individual counselling .
There was variation in the extent to which those offered group therapy accepted the treatment .
There was limited evidence that programmes which included components for increasing cognitive and behavioural skills and avoiding relapse were more effective than same length or shorter programmes without these components .
We did not find an effect of manipulating the social interactions between participants in a group programme on outcome .
AUTHORS ' CONCLUSIONS Group therapy is better for helping people stop smoking than self help , and other less intensive interventions .
There is not enough evidence to evaluate whether groups are more effective , or cost-effective , than intensive individual counselling .
There is not enough evidence to support the use of particular psychological components in a programme beyond the support and skills training normally included | BACKGROUND Group therapy offers individuals the opportunity to learn behavioural techniques for smoking cessation , and to provide each other with mutual support .
OBJECTIVES We aim ed to determine the effects of smoking cessation programmes delivered in a group format compared to self-help material s , or to no intervention ; to compare the effectiveness of group therapy and individual counselling ; and to determine the effect of adding group therapy to advice from a health professional or to nicotine replacement .
We also aim ed to determine whether specific components increased the effectiveness of group therapy .
We aim ed to determine the rate at which offers of group therapy are taken up . | Tobacco use is the single most important preventable cause of death in military personnel . The purpose of this r and omized clinical trial was to evaluate the effectiveness of two behavioral interventions when added to nicotine-replacement therapy on smoking cessation . The sample of 512 included 52 % active duty military , 29 % family , 11 % retirees , and 8 % Department of Defense civilians . There was a main effect of compliance at the end of the program ( EOP ) ; 69 % of those who attended 75 % of the classes were abstinent from tobacco ; regression analysis found the more intensive program to be twice as effective at EOP and at 3 months , an outcome not continued at 6 months . The longer , more intensive V and erbilt University Medical Center program was significantly more effective at helping the civilian portion of the population ( 85 % versus 60 % in the American Cancer Society program ) but not the active duty participants Subjects ( N = 139 ) were assigned to intensive behavioral or to low-contact smoking treatment and to 2-mg nicotine gum or to placebo gum in a 2 X 2 factorial design . The 2-mg gum produced higher abstinence rates than did the placebo . Subjects receiving the low-contact condition plus the 2-mg nicotine gum had excellent abstinence rates at both 26 weeks ( 56 % abstainers ) and 52 weeks ( 50 % abstainers ) . Smokers who scored at the median on a measure of physical dependence to nicotine were more likely to benefit by nicotine gum treatment than subjects who scored either higher or lower , but this relation was nonsignificant . The results of this study are compared with an earlier nonblind trial Sustained-release bupropion and nortriptyline have been shown to be effcacious in treating cigarette smoking . Psychological intervention is also recognized as efficacious . The cost and cost-effectiveness of the 2 drug therapies have not been estimated . It was hypothesized that nortriptyline would be more cost-effective than bupropion . Hypotheses were not originally proposed concerning the cost-effectiveness of psychological versus drug treatment , but the 2 were compared using exploratory analyses . This was a 3 ( bupropion versus nortriptyline versus placebo ) by 2 ( medical management alone versus medical management plus psychological intervention ) r and omized trial . Participants were 220 cigarette smokers . Outcome measures were cost and cost-effectiveness computed at week 52 . Nortriptyline cost less than bupropion . Nortriptyline was more cost-effective than bupropion ; the difference was not statistically significant . Psychological intervention cost less than the 2 drug treatments , and was more cost-effective , but not significantly so . Prospect i ve investigations of the cost and cost-effectiveness of psychological and pharmacological intervention , using adequate sample sizes , are warranted Objective - To compare the effectiveness of two different stop smoking interventions . Design - A r and omised , controlled trial . Results based on intention to treat . Setting - Three towns in the south-eastern part of Norway . Interventions - Visits to GP for " practice as usual " ( GP group ) or participation in the behavioural programme SmokEnders ( SE group ) with follow-up 2 weeks , 2 months and 1 year after an agreed stopping date . Subjects - 139 smokers recruited through open invitation . Main outcome measure - Self-reported smoking stop rate 2 weeks , 2 months and 1 year after an agreed stopping date , completed with biochemical indicators by the 1-year registration . Results ? Two weeks after the agreed cessation date , 10/70 ( 14 % ) of the GP group and 46/69 ( 67 % ) of the SE group had stopped smoking . After 2 months , 9/70 ( 13 % ) in the GP group and 37/69 ( 54 % ) in the SE group were non-smokers . One year after cessation 5/70 ( 7 % ) in the GP group and 21/69 ( 30 % ) in the SE group were non-smokers . Conclusions ? Both interventions were effective as measured by the smoking cessation rate . However , the intervention in the SE group was considerably more effective than in the GP group , which suffered from a sizeable number of drop-outs BACKGROUND Sustained-release bupropion hydrochloride and nortriptyline hydrochloride have been shown to be efficacious in the treatment of cigarette smoking . It is not known whether psychological intervention increases the efficacy of these antidepressants . This study compared both drugs with placebo . It also examined the efficacy of these 2 drugs and placebo with and without psychological intervention . METHODS This was a 2 ( medical management vs psychological intervention ) x 3 ( bupropion vs nortriptyline vs placebo ) r and omized trial . Participants were 220 cigarette smokers . Outcome measures were biologically verified abstinence from cigarettes at weeks 12 , 24 , 36 , and 52 . RESULTS Psychological intervention produced higher 7-day point-prevalence rates of biochemically verified abstinence than did medical management alone . With the use of point-prevalence abstinence , both nortriptyline and bupropion were more efficacious than placebo . On rates of 1-year continuous abstinence , the 2 drugs did not differ from each other or from placebo . Psychological intervention did not differ from medical management alone on rates of 1-year continuous abstinence . CONCLUSIONS Both nortriptyline and bupropion are efficacious in producing abstinence in cigarette smokers . Similarly , psychological intervention produces better abstinence rates than simple medical management . Both drugs , and psychological intervention , have limited efficacy in producing sustained abstinence . The data also suggest that combined psychological intervention and antidepressant drug treatment may not be more effective than antidepressant drug treatment alone Following an initial smoking program , 33 subjects were r and omly assigned to one of four maintenance strategy conditions developed to investigate the Marlatt and Gordon cognitive-behavioral model of relapse . Two out of three components of the model were supported . Abstinent subjects given problem solving training did not show significant relapse while those given an attention placebo control did relapse significantly . Self-efficacy expectations predicted smoking rate up to 5-month follow-up . Contrary to expectations based on the Marlatt and Gordon model , subjects taught to cope with the guilt and sense of personal failure associated with a relapse episode showed considerable relapse The present investigation assessed the effectiveness of nicotine fading as a non-aversive alternative to oversmoking . Subjects ( 66 women and 64 men ) were r and omly assigned to oversmoking , nicotine fading , nicotine fading/smokeholding , and a nonmaintenance control . Results failed to indicate the expected superiority of nicotine fading/maintenance over the control condition . Instead , the addition of smokeholding appeared to produce a significant incremental effect over nicotine fading alone . Unfortunately , 12-month follow-up revealed considerable relapse across conditions and no significant treatment effects . Even so , absolute outcome for nicotine fading/smokeholding was encouraging . This procedure is both safe and apparently very acceptable to subjects . If the current results can be replicated , a clinical ly effective technique will have been established with applicability in both clinic and self-help setting This study is a r and omized , double-blind , placebo-controlled clinical trial examining the effects of an intensive cognitive-behavioral mood management treatment ( CBTD ) and of bupropion , both singularly and in combination , on smoking cessation in adult smokers . As an extension of our previous work , we planned to examine the synergistic effects of CBTD and bupropion on smoking cessation outcomes in general and among smokers with depression vulnerability factors . Participants were 524 smokers ( 47.5 % female , M ( age ) = 44.27 years ) who were r and omized to one of four 12-week treatments : ( a ) st and ard , cognitive-behavioral smoking cessation treatment ( ST ) plus bupropion ( BUP ) , ( b ) ST plus placebo ( PLAC ) , ( c ) st and ard cessation treatment combined with cognitive-behavioral treatment for depression ( CBTD ) plus BUP , and ( d ) CBTD plus PLAC . Follow-up assessment s were conducted 2 , 6 , and 12 months after treatment , and self-reported abstinence was verified biochemically . Consistent with previous studies , bupropion , in comparison with placebo , result ed in better smoking outcomes in both intensive group treatments . Adding CBTD to st and ard intensive group treatment did not result in improved smoking cessation outcomes . In addition , neither CBTD nor bupropion , either alone or in combination , was differentially effective for smokers with single-past-episode major depressive disorder ( MDD ) , recurrent MDD , or elevated depressive symptoms . However , findings with regard to recurrent MDD and elevated depressive symptoms should be interpreted with caution given the low rate of recurrent MDD and the low level of depressive symptoms in our sample . An a priori test of treatment effects in smokers with these depression vulnerability factors is warranted in future clinical trials This article describes the test of the hypothesis that a cognitive-behavioral mood management intervention would be effective for smokers with a history of major depressive disorder ( MDD ) . The method was r and omized trial ; the assessment s occurred at Weeks 0 , 8 , 12 , 26 , and 52 . Ss were 149 smokers ; 31 % had a history of MDD . All received 2 mg of nicotine gum . Mood management was provided in 10 group sessions over 8 weeks . St and ard treatment was provided in 5 group sessions over 8 weeks . Outcome was continuous abstinence . History-positive Ss were more likely to be abstinent when treated with mood management . Treatment condition differences were not significant for history-negative Ss . For history-positive Ss , less anger at baseline predicted abstinence . For history-negative Ss , more years smoked and higher baseline carbon monoxide ( CO ) predicted abstinence . Cognitive-behavioral therapy did not affect mood after quitting . Abstinence predictors differed as a function of baseline diagnosis Abstract The role of aversive conditioning in rapid smoking was examined by r and omly assigning smokers to one of three aversive treatments design ed to induce three distinct levels of central malaise . These treatments , full-scale rapid smoking ( FS ; n = 22 ) , truncated rapid smoking ( TC : n = 20 ) and rapid puffing ( RP ; n = 20 ) were combined with a full-scale counseling package . A fourth treatment , full-scale rapid smoking with reduced counseling ( RC ; n = 20 ) , was included to evaluate the contribution of coping response training to rapid-smoking efficacy . Among post-treatment measures of aversion , only heart rate ( HR ) response to cigarettes discriminated groups , with FS Ss exhibiting an apparent conditioned cardiac acceleration to cigarettes . Six-month follow-up data revealed that both the type of counseling and level of aversion had an impact on cigarette abstinence . At 6-months post-treatment , the FS group produced the best outcome , while the TC group and the RC group had the worst outcomes . The RP group was intermediate to these groups . Regression analysis showed that across all groups , confidence ratings of remaining abstinent were most predictive of outcome whereas within the two full-scale rapid-smoking treatments , post-treatment HR response to cigarettes was most predictive of latency to relapse . The results were discussed with respect to the contributions of aversion conditioning and full counseling to the success of aversive treatment packages for smoking cessation BACKGROUND New training programs need to be developed to help Chinese smokers achieve quitting . The objective of this study was to assess the effectiveness of a group smoking cessation intervention based on social cognitive theory among Chinese smokers . METHOD A total of 225 smokers were eligible for the study and were r and omly assigned to an intervention group ( n=118 ) and a control group ( n=107 ) . The intervention group received the course soon after a baseline survey , whereas the control group received routine training in the first 6 months , and then took the same course . Effectiveness was evaluated at 6-month and 1-year follow-up from baseline . RESULTS After 6 months , 40.5 % ( 47/116 ) in the intervention group and 5.0 % ( 5/101 ) in the control group quit smoking ( absolute risk reduction : 35.5 % [ 95 % confidence interval ( CI ) : 24.2 - 46.8 % ] ) . The 6-month continuous abstinence rate was 28.4 % ( 33/116 ) in the intervention group and 3.0 % ( 3/101 ) in the control group ( absolute risk reduction 25.4 % [ 95 % CI : 15.6 - 35.2 % ] ) . At 1-year follow-up , the proportion of quitting and the 6-month abstinence rate in the intervention group were 35.8 % and 22.0 % , respectively . The factors associated with smoking cessation during the 6 month period were intervention ( adjusted odds ratio [OR]=6.42 [ 95 % CI : 2.46 - 13.28 ] ) , as well as anticipation of quitting ( adjusted OR=1.46 [ 95 % CI : 1.12 - 1.91 ] ) and skill self-efficacy score in the baseline ( adjusted OR=1.04 [ 95 % CI : 1.01 - 1.07 ] ) . The same intervention was conducted in the control group after the 6-month study , in which a similar intervention effect was observed . CONCLUSION A smoking cessation intervention based on social cognitive theory among Chinese smokers is highly effective OBJECTIVE Schizophrenic patients have high rates of cigarette smoking . The authors compared the outcomes of two group psychotherapy programs for smoking cessation in patients with schizophrenia or schizoaffective disorder who were also treated with the nicotine transdermal patch and with either atypical or typical antipsychotic medications . METHOD Forty-five subjects were r and omly assigned to 1 ) the group therapy program of the American Lung Association ( N=17 ) or 2 ) a specialized group therapy program for smokers with schizophrenia ( N=28 ) that emphasized motivational enhancement , relapse prevention , social skills training , and psychoeducation . All subjects participated in 10 weeks of treatment with the nicotine transdermal patch ( 21 mg/day ) and 10 weekly group therapy sessions and continued to receive their pre study atypical ( N=18 ) or typical ( N=27 ) antipsychotic medications . Outcome variables included treatment retention , rate of smoking abstinence , and expired-breath carbon monoxide level . RESULTS Smoking abstinence rates did not differ in the two group therapy programs . However , atypical antipsychotic agents , in combination with the nicotine transdermal patch , significantly enhanced the rate of smoking cessation ( 55.6 % in the atypical agent group versus 22.2 % in the typical group ) , which was reflected by a significant effect of atypical versus typical agents on carbon monoxide levels . Risperidone and olanzapine were associated with the highest quit rates . CONCLUSIONS The results suggest that 1 ) smoking cessation rates with the nicotine transdermal patch are modest in schizophrenia , 2 ) specialized group therapy for schizophrenic patients is not significantly different from American Lung Association group therapy in its effect on smoking cessation , and 3 ) atypical agents may be superior to typical agents in combination with the nicotine transdermal patch for smoking cessation in schizophrenia The authors examined patterns of change in depressive symptoms during smoking cessation treatment in 163 smokers with past major depressive disorder ( MDD ) . Cluster analysis of Beck Depression Inventory ( A. T. Beck , C. H. Ward , M. Mendelson , J. Mock , & J. Erbaugh , 1961 ) scores identified 5 patterns of change . Although 40 % of participants belonged to clusters characterized by increasing depressive symptoms during quitting ( rapid increasers , n = 31 , and delayed increasers , n = 35 ) , almost 47 % were in clusters characterized by decreasing symptoms ( delayed decreasers , n = 24 , and rapid decreasers , n = 52 ) . Both rapid and delayed increasers had especially poor smoking cessation outcomes . Results suggest that among smokers with an MDD history there is substantial heterogeneity in patterns of depressive symptoms during quitting and that patterns involving increased symptoms are associated with low abstinence rates OBJECTIVE To assess the impact and costs of coverage for tobacco dependence treatment benefits with no patient cost sharing for smokers with employer sponsored coverage in two large independent practice association ( IPA ) model health maintenance organisations ( HMOs ) in California , USA . METHODS A r and omised experimental design was used . 1204 eligible smokers were r and omly assigned either to the control group , which received a self-help kit ( video and pamphlet ) , or to the treatment group , which received the self-help kit and fully covered benefits for over the counter ( OTC ) nicotine replacement therapy ( NRT ) gum and patch , and participation in a group behavioural cessation programme with no patient cost sharing . RESULTS The quit rates after one year of follow up were 18 % in the treatment group and 13 % in the control group ( adjusted odd ratio ( OR ) 1.6 , 95 % confidence interval ( CI ) 1.1 to 2.4 ) , controlling for health plan , sociodemographics , baseline smoking characteristics , and use of bupropion . Rates of quit attempts ( adjusted OR 1.4 , 95 % CI 1.1 to 1.8 ) and use of nicotine gum or patch ( adjusted OR 2.3 , 95 % CI 1.6 to 3.2 ) were also higher in the treatment group . The annual cost of the benefit per user who quit ranged from $ 1495 to $ 965 or from $ 0.73 to $ 0.47 per HMO member per month . CONCLUSIONS Full coverage of a tobacco dependence treatment benefit implemented in two IPA model HMOs in California has been shown to be an effective and relatively low cost strategy for significantly increasing quit rates , quit attempts , and use of nicotine gum and patch in adult smokers This research tested a multicomponent self-help manual that contained nicotine fading and some behavioral techniques . It also evaluated the incremental effects of using higher amounts of therapist contact on quitting rates . 114 smokers were r and omly assigned to one of four treatment groups : ( 1 ) A 10-session multicomponent program ( n = 25 ) ; ( 2 ) a 5-session multicomponent program ( n = 31 ) ; ( 3 ) a 5-session multicomponent plus a self-help manual program ( n = 25 ) ; and ( 4 ) a self-help-manual-only program ( n = 33 ) . A control group ( n = 48 ) did not receive any treatment . The distinctive characteristic of the treatments was the different amount of therapist contact . Common components of the programs were a refundable deposit , self-monitoring , information on smoking , stimulus control , CO feedback , nicotine fading , and strategies to avoid withdrawal symptoms . End-of-treatment quit rates ranged from 36 % ( self-help manual ) to 68 % ( 10-session multicomponent program ) . At 12-month follow-up there were significant differences between groups , and the most effective group was the 5-session plus manual group , with an abstinence rate of 48 % OBJECTIVE : To determine the efficacy and safety of clonidine versus placebo in smoking cessation . DESIGN : Single-center , r and omized , double-blind , parallel- design comparison of transdermal clonidine with behavior modification , transdermal clonidine without behavior modification , placebo with behavior modification , and placebo without behavior modification . SETTING : Outpatient , university-based ambulatory care facility . PATIENTS : One hundred fifty generally healthy , highly nicotine-dependent cigarette smokers . INTERVENTION : Clonidine was given as the transdermal patch initiated 72 hours prior to smoking-cessation attempts and continued for six weeks thereafter . Clonidine was given at a dose of 0.2 mg/d for patients weighing more than 150 pounds ( > 67.5 kg ) and at a dose of 0.1 mg/d for patients weighing less than 150 pounds ( < 67.5 kg ) . Behavior modification consisted of a total of 12 one-hour structured group training sessions . Patients not receiving behavior modification received printed material , which included the “ Help Quit Kit ” and the “ I Quit Kit ” from the American Cancer Society . MAIN OUTCOME MEASURES : Smoking-cessation rates were assessed at 6 , 12 , 24 , and 52 weeks of follow-up . In addition , adverse reactions to clonidine or placebo were evaluated . RESULTS : Clonidine with behavior modification was statistically superior to the other three treatment groups but only at 6 weeks of follow-up . There were no differences in smoking-cessation rates among any of the treatment groups at any other follow-up intervals . Patients receiving behavior modification , regardless of whether they received clonidine , had better quit rates than patients not receiving behavior modification at all follow-up times except 52 weeks . Women receiving clonidine had significantly better quit rates than men receiving clonidine at all follow-up visits . Clonidine was associated with a significantly higher incidence of adverse effects than placebo ( 52 vs. 11 percent ) . However , the number of smokers withdrawing from the study was not greater with clonidine compared with placebo ( 9 vs. 7 percent , respectively ) . CONCLUSIONS : Clonidine is probably not effective as a pharmacologic adjunct to behavior modification in smoking cessation . It may have a potential role in women smokers who do-not respond to or can not tolerate more traditional smoking-cessation therapies BACKGROUND Weight gain after smoking cessation is often cited by women smokers as a primary reason for not attempting to quit smoking or for relapsing after a cessation attempt . METHODS A r and omized trial of 417 women smokers was conducted to test the addition of two weight control strategies to a smoking cessation program . Participants received the st and ard smoking cessation program , the program plus nicotine gum , the program plus behavioral weight control , or the program plus both nicotine gum and behavioral weight control . Weight and smoking status were measured at the end of treatment and at 6 and 12 months posttreatment . RESULTS Smoking cessation rates were highest in the group receiving the smoking cessation program plus nicotine gum . Weight gain did not vary by treatment condition , so its effect on relapse could not be examined by group . There was no significant relationship between weight gained and relapse in individuals . CONCLUSIONS The added behavioral weight control program was attractive to the participants and did not reduce smoking cessation rates . However , it did not produce the expected effect on weight , thereby restricting our ability to examine the effect of weight control on smoking cessation and relapse The effectiveness of two commercially available smoking cessation manuals was evaluated under minimal therapist contact conditions . Forty cigarette smokers who volunteered to participate in a self-help quit smoking program were r and omly assigned to one of three conditions : 18 to Pomerleau and Pomerleau 's 1977 manual , 13 to Danaher and Lichtenstein 's 1978 manual , and nine to a waiting-list control . Six-month follow-ups indicate that the former manual offers a useful treatment approach , while no firm conclusions can be made regarding the latter manual . Utility of self-help manuals in multilevel treatment programs is discussed Smokers ( N = 126 ) were r and omly assigned to 6-session smoking cessation treatments consisting of 1 of 2 counseling strategies ( skills training or support ) and 1 of 2 nicotine exposure strategies ( nicotine gum or rapid smoking ) . Counseling and nicotine strategies were completely crossed ; all four combinations result ed in equivalent 1-year abstinence rates . Skills training produced higher initial cessation and more coping responses posttreatment than did support . Rapid smoking , but not nicotine gum , produced tachycardia to the taste of cigarettes posttreatment , consistent with cigarette aversion . The treatments were differentially effective among sub population s of smokers : Subjects high in pretreatment negative affect responded best to support counseling ; those low in pretreatment negative affect responded best to skills training . Self-reports of pretreatment craving predicted response to the nicotine exposure treatments This study examined the relationship between depression history and smoking after a quit attempt . A total of 677 smokers participating in a r and omized smoking cessation trial ( Smith et al. , 2001 ) provided data on current depression , depression history , and depression-related measures and smoking at 1 week and 6 months after a quit date . Depression history predicted smoking at 1 week postquit but not at 6 months postquit . Smoking during the first week was not predictive of smoking at 6 months in those with a history of depression but was predictive among those with no history of depression . Prediction models including depression history and depression-related measures ( e.g. , negative affect , negative cognitive style ) showed that depression history was a powerful predictor of smoking early in the quit attempt Clients in substance abuse treatment are at high risk for smoking-related illness due to higher rates and heavier smoking than the general population . Three myths widely held by both treatment staff and substance abusers in treatment-people in treatment do not want to quit smoking , people in treatment will relapse to other drug use if they attempt to quit smoking , and people in treatment are unable to quit smoking-make it difficult to broach the matter of smoking cessation . A 16-week , cognitive-behavioral group program with nicotine patches was conducted at Oregon 's largest , private , nonprofit substance abuse treatment agency . Of 490 clients , approximately 85 % of whom smoke , 106 ( 25 % of the smokers ) were interested enough in quitting to attend an orientation . Approximately 40 % of these were methadone maintenance clients . The others were distributed among two residential and two outpatient drug-free treatment services . Of 90 assigned , 68 began voluntary treatment , and 21 were assigned to delayed treatment . Of the 66 smokers who began , 74 % succeeded in quitting smoking for at least 1 day , and 23 % were abstinent for at least 4 continuous weeks . At the end of the 16-week treatment , 7 subjects ( 11 % ) were abstinent . No control subjects quit smoking on their own . The article discusses issues of institutionalizing smoking cessation services in drug treatment agencies Context Although there are many health benefits for smokers who stop smoking , we still lack evidence from r and omized , controlled trials that smoking cessation programs reduce mortality . Contribution In this r and omized , controlled trial of a 10-week-long smoking cessation intervention in 5887 smokers with asymptomatic airway obstruction , 14-year mortality rates were higher in the usual care group than in the smoking cessation group ( hazard ratio , 1.18 [ 95 % CI , 1.02 to 1.37 ] ) . The mortality benefit was greatest among the 21.7 % of the intervention group who actually managed to quit smoking . Implication s Smoking cessation programs substantially reduce mortality even when only a minority of patients stop smoking . The Editors Smoking cessation almost certainly has beneficial effects on subsequent mortality ( 1 ) . However , the strongest support for this assertion comes from cohort studies , where smokers and quitters were self-selected . Results from r and omized trials , which avoid the selection issue , have largely been disappointing because mortality benefits have not been clear or have not been clearly attributable to smoking cessation ( 1 ) . The Lung Health Study ( LHS ) was a r and omized clinical trial of smoking cessation and inhaled bronchodilator ( ipratropium ) therapy in smokers 35 to 60 years of age who did not consider themselves ill but had evidence of mild to moderate airway obstruction ( 2 ) . Individuals with serious disease , hypertension , obesity , or excessive alcohol intake were excluded . The primary research questions were whether a smoking cessation program and use of inhaled ipratropium would decrease the rate of decline of lung function and would affect mortality and morbidity over 5 years . These results have been reported elsewhere ( 3 , 4 ) . The smoking cessation program was associated with cumulative reduced decline in lung function ( FEV1 ) that was largest in participants who stopped smoking early in the study ; inhaled ipratropium produced a small noncumulative increase in FEV1 that disappeared when the drug was withdrawn ( 3 ) . Intention-to-treat analysis after 5 years did not reveal differences in morbidity or mortality among treatment groups ( 4 ) , although subgroup analysis showed that smoking cessation was associated with significant reductions in fatal or nonfatal cardiovascular disease and coronary heart disease . This paper reports the effects of the study intervention on mortality in LHS participants 14.5 years after r and omization . Methods The design of the LHS has been described in detail elsewhere ( 2 ) . The participants , all volunteers , were smokers who did not consider themselves ill but had evidence of airway obstruction and little evidence of other disease . Research ers recruited participants from the community using a wide variety of techniques ( 5 ) . In 10 clinical centers , 5887 participants were r and omly assigned to 3 groups . Two special intervention groups received an intensive 10-week smoking cessation program . Briefly , the cessation intervention consisted of a strong physician message and 12 two-hour group sessions , using behavior modification and nicotine gum . Quitters entered a maintenance program that stressed coping skills . One special intervention group also received ipratropium , while the other received a placebo inhaler . A third group received usual care . About 75 % of the original participants were followed continuously for the subsequent 10 years by biannual telephone contacts and 1 clinic visit at approximately 11 to 12 years after r and omization ( 6 ) . Telephone contacts served to check smoking status , morbidity , and mortality and were not part of the intervention . All study participants provided written informed consent for the original LHS before beginning the study . The consent documents stated that smoking increases the risk for chronic obstructive pulmonary disease , respiratory tract cancer , and cardiovascular disease and that smoking cessation would decrease such risks . Additional written informed consent was obtained from persons who participated in the biannual telephone calls . Institutional review boards at each of the 10 clinical centers and the coordinating center approved the study design and consent documents . When biannual phone calls revealed a participant death , staff attempted to collect death certificates , autopsy reports , relevant medical records , and interviews with attending physicians or eyewitnesses . An independent mortality and morbidity review board examined these data and classified causes of death . In addition , a National Death Index review provided date and cause of death for all U.S. study participants through the end of 2001 . Vital status at 31 December 2001 or 14.5 years , whichever was earlier , was successfully determined for 98.3 % of all participants ; missing individuals were Canadians who had been lost to follow-up and were not accessible through the National Death Index . Mortality end points were classified in 7 categories : coronary heart disease , cardiovascular disease including coronary heart disease , lung cancer , other cancer , respiratory disease excluding lung cancer , other , and unknown . The other category included but was not limited to liver disease , kidney disease , sepsis , accidents , suicide , and AIDS . Analyses were performed on an intention-to-treat basis , comparing the special intervention group with the usual care group . The special intervention group was a combination of the groups originally assigned to receive inhaled ipratropium or placebo therapy . Both of these groups , which were very similar at baseline , received the smoking cessation program and exhibited similar rates of smoking cessation ( 3 ) . Participants were also divided into 3 groups according to smoking history during the initial 5 years of the trial . Sustained quitters were participants who stopped smoking in the first year after r and omization and maintained biochemically vali date d abstinence ( 3 ) throughout follow-up . Continuing smokers were participants who reported smoking at all follow-up visits . Intermittent quitters were participants who reported smoking at some but not all of their follow-up visits or during the time between visits . Statistical Analysis Baseline differences between the special intervention and usual care groups were tested by using t-tests for continuous variables and chi-square statistics for categorical variables . Cause-specific death rates and times to events were analyzed by using the KaplanMeier product-limit method ( 7 ) . Survival was compared among groups by using the log-rank test . Hazard ratios and adjusted analyses were obtained by using the Cox proportional hazards model . Interactions were assessed by comparing hierarchically related proportional hazards models . All P values result from 2-sided tests ; no adjustments were made for multiple comparisons . Role of the Funding Source This study was funded by a contract and grants from the National Heart , Lung , and Blood Institute of the National Institutes of Health . The funding source had a role in the design of the study and approved the manuscript before it was su bmi tted for publication . Results Baseline characteristics of LHS participants are shown in Table 1 . Most were middle-aged ; smoked heavily ; and had substantial smoking histories , airway obstruction ( FEV1FVC ratio 70 % ) , and borderline low FEV1 values . On average , participants were normotensive and had normal body mass indices . Most participants were of white ethnicity ; 37 % were women . The average participant had some post secondary education and did not drink heavily . The special intervention and usual care groups did not significantly differ at baseline , except in percentage of participants who were married , which was higher in the special intervention group ( P= 0.04 ) . Smoking status after the first 5 years differed significantly between treatment groups ( P 0.001 ) . Among special intervention participants and usual care participants , respectively , 21.7 % and 5.4 % were sustained quitters , 29.3 % and 23.3 % were intermittent quitters , and 49.0 % and 71.3 % were continuing smokers . Table 1 . Baseline Characteristics of Lung Health Study Participants There were 731 known deaths among LHS participants , as shown in Table 2 . Lung cancer was the most common cause of death ( n= 240 [ 33 % ] ) . Coronary heart disease accounted for 77 deaths ( 10.5 % ) , and cardiovascular disease including coronary heart disease accounted for 163 deaths ( 22 % ) . One hundred fifty-four participants ( 21 % ) died of cancer of organs other than the lung . Deaths due to respiratory disease other than cancer were relatively uncommon ( n= 57 [ 7.8 % ] ) . The cause of death was unknown in only 17 participants ( 2.3 % ) . Mortality did not significantly differ between the special intervention groups originally assigned to ipratropium or placebo ( Table 2 ) . Table 2 . Causes of Death by Treatment Group Figure 1 shows all-cause survival rates in the 2 treatment groups . Death rates were significantly higher in the usual care group than in the special intervention group ( 10.38 per 1000 person-years vs. 8.83 per 1000 person-years ; P= 0.03 ) . The hazard ratio for mortality in the usual care group was 1.18 ( 95 % CI , 1.02 to 1.37 ) compared with the special intervention group . Figure 2 shows categorical causes of death in the 2 treatment groups . In all categories except other , death rates were higher in the usual care group than in the special intervention group , but the difference was significant only for deaths from respiratory diseases not related to lung cancer ( 1.08 per 1000 person-years vs. 0.56 per 1000 person-years ; P= 0.01 ) . Figure 1 . All-cause 14.5-year survival . P Figure 2 . Mortality rates at 14.5 years by cause . When survival was analyzed according to smoking habit , it differed significantly between groups ( P < 0.001 ) , even after adjustment for baseline differences ( data not shown ) . Mortality was 6.04 per 1000 person-years in sustained quitters , 7.77 per 1000 person-years in intermittent quitters , and 11.09 per 1000 A multicomponent smoking relapse prevention treatment based on Marlatt and Gordon 's ( 1980 ) model of the relapse process was developed and evaluated . Behavior-analytic methods were used to develop assessment instruments , training situations , and coping responses . The prevention components were presented in the context of a basic broad-spectrum stop-smoking program , and were compared with the basic program plus discussion control , and the basic program alone . Smoking-related dependent variables generally did not differ between groups at any time from pre-treatment to 12 month follow-up . Only the subjects in the relapse prevention condition improved problem-solving and social skills needed to cope with high-risk situations . These subjects also tended to take longer to relapse and smoke fewer cigarettes at the time of relapse . Subjects above the median level of competence on measures of social skill at post-treatment remained abstinent significantly longer . Maintenance of non-smoking was found to be related to the degree of competence with which individuals deal with high-risk situations . Results are discussed in relation to models of compliance with therapeutic regimens Two studies tested the utility of self-control procedures and covert sensitization as alternatives to rapid smoking in smoking cessation . Subjects were at least 21 years old and had smoked at least one pack per day for at least 5 years . Relaxation training and discussion of goals were given in three meetings per week for 2 weeks prior to subject-chosen quit date s. A total of 10 sessions was held during the 90 days following cessation . In Study I , both groups received self-control strategies . One group also received covert sensitization . At 3-month follow-up , 33 % of those without and 27 % of those with covert sensitization were abstinent . At 6-month follow-up these percentages were 33 and 13 , respectively . Covert sensitization apparently added nothing to the effects of the self-control package . In Study II , one group received the same combination of self-control manual and the basic package as in Study I. A second group received the basic package with cue extinction procedures design ed to extinguish associations between desires for cigarettes and cues paired with previous smoking . A third group received a combination of both sets of procedures . At 3-month follow-up , 71 and 60 % , respectively , of the first two groups were abstinent , while only 31 % of the combination group was abstinent . At 6-month follow-up , these percentages were 29 , 27 , and 8 , respectively . The low abstinence rate for the combination group likely reflects problems associated with presenting too much material in the 2 weeks prior to cessation The present investigation initiated a dismantling strategy in which subjects were assigned to treatment stages ( preparation , aversion , maintenance ) or to combinations of stages in a factorial design . It was hypothesized that multistage conditions would be superior to single stage conditions and that maintenance would retard relapse . Forty men and 33 women were r and omly assigned to one of seven conditions . Results supported both hypotheses although significant effects were no longer evident at 12-month follow-up . Considerable relapse occurred in all conditions . Specific treatment components appeared to be of limited importance as indicated by generally very similar results for preparation and aversion . Booster sessions appeared to be ineffective . Interpretation of the findings is limited , however , by a relatively small subject enrollment in each condition . It was concluded that attempts to isolate extremely precise treatment elements are unlikely to be successful . Suggestions for further research included adoption of more structured maintenance strategies emphasizing coping skills and a more systematic focus upon potentially important process variables , notably group cohesiveness OBJECTIVE To compare the efficacy and safety of 22-mg and 44-mg doses of transdermal nicotine therapy when it is paired with minimal , individual , or group counseling to improve smoking cessation rates . DESIGN An 8-week clinical trial ( 4 weeks double-blind followed by 4 weeks open label ) using r and om assignment of participants to both dose ( 22 or 44 mg ) and counseling ( minimal , individual , or group ) conditions . PARTICIPANTS Daily cigarette smokers ( > or = 15 cigarettes per day for at least 1 year ) who volunteered to participate in a study of smoking cessation treatment . A total of 504 participants were enrolled at two sites . INTERVENTION Four weeks of 22- or 44-mg transdermal nicotine therapy followed by 4 weeks of dosage reduction ( 2 weeks of 22 mg followed by 2 weeks of 11 mg ) . Counseling consisted of a self-help pamphlet ( minimal ) ; a self-help pamphlet , a brief physician motivational message , and three brief ( < 15 minutes ) follow-up visits with a nurse ( individual ) ; or the pamphlet , the motivational message , and eight weekly 1-hour group smoking cessation counseling visits ( group ) . All participants returned weekly to turn in question naires and for assessment of their smoking status . MAIN OUTCOME MEASURES Abstinence from smoking was based on self-report , confirmed by an expired carbon monoxide concentration lower than 10 ppm . Withdrawal severity was assessed by means of an eight-item self-report question naire completed daily . RESULTS Smoking cessation rates for the two nicotine patch doses and three levels of counseling did not differ significantly at either 8 weeks or 26 weeks following the quit date . Among those receiving minimal contact , the 44-mg dose produced greater abstinence at 4 weeks than did the 22-mg dose ( 68 % vs 45 % ; P < .01 ) . Participants receiving minimal-contact adjuvant treatment were less likely to be abstinent at the end of 4 weeks than those receiving individual or group counseling ( 56 % vs 67 % ; P < .05 ) . The 44-mg dose decreased desire to smoke more than the 22-mg dose , but this effect was not related to success in quitting smoking . Transdermal nicotine therapy at doses of 44 mg produced a significantly greater frequency of nausea ( 28 % ) , vomiting ( 10 % ) , and erythema with edema at the patch site ( 30 % ) than did a 22-mg dose ( 10 % , 2 % , and 13 % , respectively ; P < .01 for each adverse effect ) . Three serious adverse events occurred during use of the 44-mg patch dose . CONCLUSIONS There does not appear to be any general , sustained benefit of initiating transdermal nicotine therapy with a 44-mg patch dose or of providing intense adjuvant smoking cessation treatment . The two doses and all adjuvant treatments produced equivalent effects at the 26-week follow-up , and the higher patch dose produced more adverse effects . Higher-dose ( 44-mg ) nicotine replacement does not appear to be indicated for general clinical population s , although it may provide short-term benefit to some smokers attempting to quit with minimal adjuvant treatment The major findings of the LHS that have been reported thus far are that an effective smoking cessation program can be developed that can produce more than a 20 % success rate in getting smokers to give up the habit permanently , and that by stopping smoking , individuals with early COPD benefit by having an initial improvement in lung function and a slowing of the annual loss of their FEV1 . The use of a bronchodilator has a short-term effect in improving the FEV1 , but it does not affect long-term changes in lung function . AHR is common in patients with mild-to-moderate COPD . The reward for a smoker to give up the habit is an initial gain in FEV1 and a subsequent close to normal annual rate of decline of this pulmonary function parameter . These results should provide a positive incentive for smokers to quit and thereby decrease the morbidity and mortality caused by the use of tobacco Background Various strategies have been used to induce lifestyle changes to reduce ischaemic heart disease ( IHD ) with various successes . The aim of Inter99 is to assess the effect on IHD incidence of individually tailored non-pharmacological intervention on lifestyle using a newly developed computer-based health educational tool . The article describes the study and baseline results . Methods From a population of 61,301 individuals two r and om sample s ( high intensity intervention group ( A ) , n = 11,708 ; low intensity intervention group ( B ) , n = 1308 ) are screened to assess their absolute risk of IHD . Those at high risk receive individual lifestyle counselling . Individuals in group A are furthermore offered lifestyle counselling in groups on smoking cessation or physical activity/diet over a 6-month period . Individuals in group B are referred to their GP . High-risk persons are re-counselled after 1 and 3 years and the whole group is re-invited after 5 years . The remaining 48,285 ( group C ) are followed by question naire . The total population is followed through central registers . Intermediate end-points are changes in lifestyle , cholesterol , blood pressure and body mass index . Final end-point is reduction in incidence of IHD . Results The r and omization leads to comparable groups . Participation rate was 52.5 % . A total of 60 % fulfilled the predetermined criteria for being at high risk for developing IHD . After an individual lifestyle counselling 41 % accepted group-based counselling . Conclusion This large r and omized population based trial discloses a noticeable need for and acceptance of lifestyle intervention in the general population . Eur J Cardiovasc Prevention Rehab 10:377 - 386 © 2003 Lippincott Williams & Wilkins Abstract OBJECTIVE : To evaluate a pilot 4-day residential smoking treatment program for smokers who had relapsed after participation in an outpatient smoking program . DESIGN : A single-arm clinical trial . Participants stayed in a supportive , smoke-free environment for 4 days during which they attended educational sessions on nutrition , exercise , and psychology . Nicotine withdrawal was treated with nicotine inhalers and patches . After discharge , participants attended monthly outpatient group sessions for 6 months . SETTING : The Durham , NC Veterans Affairs Medical Center residential unit . PARTICIPANTS : Twenty-three medical outpatient smokers . MEASUREMENTS : Seven-day point prevalence smoking abstinence was determined by self-report of zero cigarettes smoked and verified by exhaled carbon monoxide < 8 parts per million . MAIN RESULTS : Participants ’ mean age was 57.4 years ; 100 % were male ; 61 % were Caucasian ; and 39 % were African American . The mean score on the Fagerström Test for Nicotine Dependence was 7.1 ( SD 2.3 ) . Daily nicotine doses ranged from the nicotine inhaler alone to 56 mg of transdermal nicotine plus nicotine inhaler . Verified smoking abstinence on discharge ( after 4 days ) was 21/23 or 91.3 % ( 95 % confidence interval [ 95 % CI ] , 73 to 100 ) . At 6 months , the 7-day point abstinence rate was 6/23 or 26.1 % ( 95 % CI , 15 to 36 ) . CONCLUSIONS : This pilot residential smoking treatment program was design ed to assist smokers who relapsed after outpatient treatment . Four days of residential smoking therapy successfully relieved smoking withdrawal . At 6 months after discharge , participants maintained an abstinence rate comparable to other medical therapies for smoking Eighty-nine smokers were r and omly assigned to four nicotine gum treatments for smoking cessation : behavioral treatment plus a fixed schedule of nicotine gum , behavioral treatment plus an ad lib schedule , education plus a fixed schedule , and education plus an ad lib schedule . The four treatment conditions produced similar rates of abstinence ( 40.9 % to 58.3 % ) at the end of 11 weeks of treatment . However , at 6-month follow-up , the subjects who had received behavioral treatment had a significantly better abstinence rate ( 36.7 % ) than those receiving education ( 17.5 % ) . Nicotine gum schedule had no effect on treatment outcome The effectiveness of a relapse prevention program was studied in a population of 744 smokers . Subjects first attended an intensive 4-day series of 2-hr meetings in which they were trained to use more than 40 behavioral and cognitive smoking cessation techniques . At the 1-week follow-up session , those abstinent from smoking ( 79 % , carbon monoxide verified ) were r and omly assigned to one of three follow-up conditions : ( a ) a three-session skills-training program in which subjects developed and actively rehearsed individually tailored coping strategies for likely relapse situations , ( b ) a three-session discussion control condition in which subjects discussed maintenance but did not develop or rehearse coping strategies , or ( c ) a no-treatment control condition . Survival analysis indicated higher abstinence rates for the skills-training group than for the control groups throughout the following year . After 12 months , the biochemically confirmed continuous abstinence rate was higher in the skills-training group ( 41.3 % ) than in the discussion and no-treatment groups ( 34.1 % and 33.3 % , respectively ) Gender data for bupropion suggest that it may be a particularly effective smoking cessation medication for women . It is not known whether the efficacy of this pharmacotherapy differs as a function of the psychotherapy with which it is administered . This study used a two level factorial design to examine the independent and interactive effects of medication ( bupropion 300 mg/day vs. placebo ) and psychotherapy ( cognitive-behavioral therapy [ CBT ] vs. supportive therapy [ ST ] ) . In addition to testing the hypothesis that bupropion with CBT would be most effective of all the treatments , we examined medication compliance and its role in the efficacy of bupropion . Participants were 154 women , aged at least 30 years and smoking more than 10 cigarettes/day . Compliance with study medication was assessed using Medication Event Monitoring Systems ( MEMS ) over 7 weeks of treatment . Psychological interventions were delivered in 60-min weekly group sessions . Longitudinal analysis of abstinence outcomes from end of treatment ( EOT ) through 12 months after treatment revealed a significant interaction of medication and therapy . Higher abstinence rates at EOT and 3- , 6- , 9- , and 12-month follow-ups were observed when bupropion was delivered concurrently with CBT ( 44 % , 24 % , 30 % , 23 % , 17 % ) rather than with ST ( 18 % , 1 % , 8 % , 5 % , 2 % ) . The bupropion-CBT combination , however , was not clearly superior to placebo , regardless of therapy assignment . Higher rates of medication compliance were positively predictive of abstinence , and this effect was most evident in the placebo condition . Findings provide only modest support for CBT as the preferred type of intensive therapy in conjunction with bupropion in women BACKGROUND Several large and well-conducted community interventions have failed to detect an effect on prevalence of smoking . METHODS Two thous and four hundred eight daily smokers in all motivational stages were actively recruited and included in a r and omised population -based intervention study in Copenhagen , Denmark . All smokers completed a question naire and underwent a health examination and a lifestyle consultation . Daily smokers in the high intensity intervention group were offered assistance to quit in smoking cessation groups . RESULTS The vali date d abstinence rate at 1-year follow-up was 16.3 % in the high intensity group and 12.7 % in the low intensity group compared with a self-reported abstinence rate of 7.3 % in the background population . The adjusted odds ratio of abstinence in the high intervention group was significantly higher , OR = 2.2 ( 1.6 - 3.0 ) than in the background population , also in the ' intention-to-treat ' analyses , OR = 1.5 ( 1.1 - 2.0 ) . Higher socioeconomic status , higher age at onset of daily smoking , and a higher wish to quit were predictors of success . CONCLUSION In a population -based setting , using active recruitment and offering assistance to quit , it was possible to include many smokers and to achieve a significantly higher vali date d abstinence in the high intensity intervention than in the background population , even when using ' intention-to-treat ' analyses A total of 205 ( 113 male , 92 female ) nonhospitalized recovering alcoholics with > 3 months of continuous abstinence from alcohol and drugs and relatively heavy tobacco dependence ( Fagerstrom Tolerance Question naire score = 7.7 ; mean number of cigarettes per day , 26.8 ; mean number of years smoked , 24.4 ) were r and omized to st and ard treatment ( ST ) American Lung Association quit program plus nicotine anonymous meetings ( n = 70 ) , behavioral counseling plus physical exercise ( BEX ; n = 72 ) , or behavioral counseling plus nicotine gum ( BNIC ; n = 63 ) . A 3 x 4 repeated measures design was used to evaluate the effectiveness of the interventions on smoking outcome at baseline , posttreatment , and 6- and 12-month follow-ups . Self-reported smoking status was verified with biochemical and informant report . Verified self-report indicated that significantly more smokers in BEX quit by posttreatment ( 60 % ) than in either BNIC ( 52 % ) or ST ( 31 % ) , chi 2 ( 2 , N = 205 ) = 17.85 , p < .01 , but not at the 6-month ( 29 % , 27 % , and 21 % , respectively ) or 12-month ( 27 % , 27 % , and 26 % , respectively ) follow-up . Only 4 % ( 7 of 188 ) relapsed to alcohol or drugs . Alcohol relapse did not differ by treatment group or smoking status . Length of alcohol abstinence was not associated with smoking cessation outcome The aim of this study was to assess the effectiveness of relapse prevention taught as a problem-solving procedure in increasing the efficacy of a behavioral program for smoking cessation at short- and longer-term , 12-mo . follow-up . 75 smokers were assigned r and omly to two treatment groups , using an additional 40 smokers who attended an information session but did not receive any treatment session as a control group . The first group ( n = 40 ) received the st and ard behavioral multicomponent program of Becoña . The program included motivational contract , self-monitoring , information on smoking , nicotine fading , stimulus control , avoidance of withdrawal symptoms , physiological feedback , and progressive self-control . The second group ( n = 36 ) , the relapse prevention group , were given the above program and an additional component of relapse prevention using a problem solving procedure . Both groups had 8 sessions of treatment . Analysis showed that at the end of treatment abstinence in the two groups was 80.0 % and 61.1 % , respectively , at the 12-mo . follow-ups 30.0 % and 36.1 % . These differences were not significant ; however , both groups were significantly different from the control group at the end of treatment ( 0 % abstinence ) and at 12-mo . follow-ups ( 2.5 % abstinence ) . These results show that the addition of this relapse prevention does not increase the number of smokers who quit or decrease the number who relapse . Further research should focus on the process of relapse and develop more effective procedures to help maintain abstinence BACKGROUND A history of major depressive disorder ( MDD ) predicts failure to quit smoking . We determined the effect of nortriptyline hydrochloride and cognitive-behavioral therapy on smoking treatment outcome in smokers with a history of MDD . The study also addressed the effects of diagnosis and treatment condition on dysphoria after quitting smoking and the effects of dysphoria on abstinence . METHODS This was a 2 ( nortriptyline vs placebo ) x 2 ( cognitive-behavioral therapy vs control ) x 2 ( history of MDD vs no history ) r and omized trial . The participants were 199 cigarette smokers . The outcome measures were biologically verified abstinence from cigarettes at weeks 12 , 24 , 38 , and 64 . Mood , withdrawal , and depression were measured at 3 , 5 , and 8 days after the smoking quit date . RESULTS Nortriptyline produced higher abstinence rates than placebo , independent of depression history . Cognitive-behavioral therapy was more effective for participants with a history of depression . Nortriptyline alleviated a negative affect occurring after smoking cessation . Increases in the level of negative affect from baseline to 3 days after the smoking quit date predicted abstinence at later assessment s for MDD history-negative smokers . There was also a sex-by-depression history interaction ; MDD history-positive women were less likely to be abstinent than MDD history-negative women , but depression history did not predict abstinence for men . CONCLUSIONS Nortriptyline is a promising adjunct for smoking cessation . Smokers with a history of depression are aided by more intensive psychosocial treatments . Mood and diagnosis interact to predict relapse . Increases in negative affect after quitting smoking are attenuated by nortriptyline The aim of the study was to assess the effectiveness of worksite group counselling interventions design ed to prevent smoking relapse after abstinence has been achieved following 3 months therapy using group support and /or transdermal nicotine replacement therapy . After 3 months , abstinent subjects were r and omly allocated either to a counselling group led by professional psychologists ( PG ) , to a counselling group led by former smokers ( SG ) or to no intervention group ( NG ) . The 3 and 12 months abstinence were defined , respectively , as a sustained smoking cessation during the last month , and the last 9 months . Complete abstinence was confirmed by expired carbon monoxide and by urine cotinine concentrations . The abstinence rate at 3 months was 35.1 % . After 12 months abstinence rates were not statistically different in the PG , the SG and the NG ( respectively 57.8 , 53.4 and 49.6 % of those r and omised ) . In multivariate analyzes , baseline variables associated with 12 months abstinence were non-smoking family , gender ( male ) , lower daily intake of nicotine and better psychological adjustment . Mean weight gain at 3 months in abstinent versus relapsed subjects , was respectively , 4.1 and 2.4 kg . Baseline variables associated with weight gain at 3 months were higher Fagerström score , gender ( male ) and professional status ( blue collar worker ) . Group support after abstinence has been achieved did not significantly improve the abstinence . This study shows the difficulty of preventing smoking relapse with monthly group counselling . The results indicate the need to investigate further specific programmes focusing on factors such as gender , family , nicotine dependence , psychological and weight concerns/issues which may precipitate relapse Earlier research indicated that a 10-session mood management ( MM ) intervention was more effective than a 5-session st and ard intervention for smokers with a history of major depressive disorder ( MDD ) . In a 2 x 2 factorial design , the present study compared MM intervention to a contact-equivalent health education intervention ( HE ) and 2 mg to 0 mg of nicotine gum for smokers with a history of MDD . Participants were 201 smokers , 22 % with a history of MDD . Contrary to the earlier findings , the MM and HE interventions produced similar abstinence rates : 2 mg gum was no more effective than placebo . History-positive participants had a greater increase in mood disturbance after the quit attempt . Independent of depression diagnosis , increases in negative mood immediately after quitting predicted smoking . No treatment differences were found in trends over time for measures of mood , withdrawal symptoms , pleasant activities and events , self-efficacy , and optimism and pessimism . History-positive smokers may be best treated by interventions providing additional support and contact , independent of therapeutic content Smokers recruited through the medical outpatient clinics of two similar Veterans Hospitals over two successive years participated in a smoking cessation study which r and omized them between a group assigned to behavior modification clinics and a group receiving a packet of smoking cessation material in the mail . Following the second year 's clinics at the site of one of the two hospitals , an intensive media campaign , based on the content of the behavior modification program , was targeted at the study population over commercial television and radio . The six-month abstinence rate for clinic participants measured by self-report , serum thiocyanate and exhaled air carbon monoxide was 36.8 % in the group assigned to clinic followed by media , 20.2 % in the group assigned to clinic alone , and 10.6 % in the group receiving material s in the mail . The difference in cessation rates between the clinic participants who were and those who were not exposed to the media following their clinics was significant at the 0.05 significance level ( χ2=3.9 , 1 d.f ) . Logistic analysis confirmed the benefit of the media campaign The purpose of this study was to determine the efficacy of hypnosis , health education , and behaviour modification programs for cigarette smoking cessation . A r and omized clinical trial comparing these three programs and a control group was conducted in 168 volunteers . Follow-up data three weeks after completion was available in 140 subjects . Each program showed significant reductions in reported cigarette consumption and serum thiocyanate levels , an indicator of long-term cigarette consumption , compared to entry and to the control group . However , there were no significant differences between the hypnosis , health education , or behaviour modification groups with respect to the proportion who reported quitting smoking , the number cigarettes smoked or change in serum thiocyanate levels . Reported cigarette consumption ascertained six months later again showed no significant differences between these three approaches . Factors such as subject age , age at starting cigarette smoking , educational level , marital status , spouse or partners smoking did not identify subgroups with differences between treatment responses . Thus , hypnosis , health education , and behaviour modification are each effective programs for changing cigarette smoking and each is equally effective in this regard In order to identify predictors of long-term post-treatment smoking abstinence , 333 adult smokers who volunteered to participate in a smoking cessation program were asked to complete a set of question naires which measured self-efficacy , motivation , reasons for smoking , and smoking history variables . Subjects were then r and omly assigned to one of four smoking cessation interventions . Nine variables predicted abstinance up to and including one year following treatment . The importance of self-efficacy beliefs in quitting smoking was underscored This worksite study assesses the relative effectiveness of three smoking cessation programs . Computerized medical files indicated that 29 % of 13,171 employees were current smokers . Of smokers responding to a worksite-wide survey , 79 % indicated interest in a smoking cessation program ; 402 smokers agreed to participate and were r and omly allocated , within their preference for a group or self-help approach , to the three different programs . Overall , 11 % of smokers participated , an excellent rate for a large worksite . Participants were followed for 12 months ( 91 % follow-up ) . Smokers in the group preference had better short-term results than did those following the self-help approach . The Multiple Component Program had 61 % who quit , the Relapse Prevention Program had 37 % , and the American Cancer Society Quitter 's Guide had 12 % . Long-term quit rates ranged from 16 % to 26 % ; all groups exceeded the usual spontaneous quit rate of 5 % 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 Smokers registering for a televised cessation program who also expressed interest in joining a support group and who had a nonsmoking buddy were r and omly assigned to 3 conditions : no-contact control , discussion , and social support . All Ss received a self-help manual and were encouraged to watch the daily TV program . Ss in the discussion and social support conditions were scheduled to attend 3 group meetings ( one with a buddy ) . Social support Ss and buddies received training in support and relapse prevention . A 4th analysis group was composed of Ss who failed to attend any of the scheduled meetings ( no shows ) . There were strong group effects at the end of treatment . Abstinence rates were highest in the social support group , followed , in order , by the discussion group , no shows , and no-contact controls . The social support group improved outcome by increasing both the level of support and program material use ( reading the manual and watching TV ) AIM To evaluate the effectiveness of the Five-Day Plan ( FDP ) in helping smokers to stop smoking . DESIGN R and omized controlled trial comparing intervention and control groups . The primary outcome measure was 12 months continuous abstinence verified by expired air carbon monoxide concentration . Secondary outcome measures were self-reported abstinence at end of treatment , at 3 and 6 months . SETTING Six towns in France . PARTICIPANTS 228 smokers , recruited by newspaper and radio advertisement , aged 18 years or over and willing to make an attempt to quit smoking . INTERVENTION The Intervention group ( 119 participants ) received the FDP , which is a behavioural group-based treatment programme that has been in operation in France since 1965 . It involves five consecutive evening behavioural therapy sessions . The Control group ( 109 participants ) received a single session discussing the health effects of smoking . FINDINGS In the Intervention group , 67 participants ( 56 % ) quit smoking at the end of the FDP . After three months this number had been reduced to 30 ( 25 % ) and to 19 ( 16 % ) by the end of one year . In the Control group these numbers were 14 ( 13 % ) and 12 ( 11 % ) , respectively , after three and 12 months . When considering the rate of cessation without lapse after one year a significant difference was observed with a 13 % rate in the Intervention group and 3 % in the Control group ( P = 0.004 ) . CONCLUSIONS The FDP may be considered as an aid for smokers who want to quit Described an examination of data collected 2 years following the onset of a media-based , worksite smoking cessation intervention . Thirty-eight companies in Chicago were r and omly assigned to one of two experimental conditions . In the inital 3-week phase , all participants in both conditions received self-help manuals and were instructed to watch a 20-day televised series design ed to accompany the manual . In addition , participants in the group ( G ) condition received six sessions emphasizing quitting techniques and social support . In the second phase , which continued for 12 months , employees in G participated in monthly peer-led support groups and received incentives , while participants in the nongroup ( NG ) condition received no further treatment . Twenty-four months after pretest , 30 % of employees in G were abstinent compared to only 19.5 % in NG . This study is one of the few experimentally controlled worksite smoking cessation interventions to demonstrate significant program differences 2 years following the initial intervention This study compared the efficacy of 2 traditional methods of smoking cessation , gradual reduction and " cold turkey , " with a new approach involving variation in the intercigarette interval . One hundred twenty-eight participants quit smoking on a target date , after a 3-week period of ( a ) scheduled reduced smoking ( progressive increase in the intercigarette interval ) , ( b ) nonscheduled reduced smoking ( gradual reduction , no specific change in the intercigarette interval ) , ( c ) scheduled nonreduced smoking ( fixed intercigarette interval , no reductions in frequency ) , or ( c ) nonscheduled nonreduced smoking ( no change in intercigarette interval or smoking frequency ) . Participants also received cognitive-behavioral relapse prevention training . Abstinence at 1 year averaged 44 % , 18 % , 32 % , and 22 % for the 4 groups , respectively . Overall , the scheduled reduced group performed the best and the nonscheduled reduced group performed the worst . Both scheduled groups performed better than nonscheduled ones . Scheduled reduced smoking was associated with reduced tension , fatigue , urges to smoke , withdrawal symptoms , increased coping effort ( ratio of coping behavior to urges ) , and self-efficacy , suggesting an improved adaptation to nonsmoking and reduced vulnerability to relapse Two methods of nicotine fading as a smoking cessation preparation technique were compared . A br and -switching procedure and a three-stage set of " Nicotine Faders " graduated filters were the preparation strategies . Both methods implemented a putative 30 - 50 - 80 % nicotine exposure reduction schedule in three weekly phases . There were a total of 110 study participants ( 57 in br and switching ) enrolled in eight clinic groups . Results indicated that at the 80 % reduction level , meaningful reductions in nicotine ( measured by its metabolite cotinine ) and carbon monoxide ( CO ) exposure were measurable with both nicotine fading procedures . Overall pooled nicotine and CO exposure drops from baselines of 48.2 % and 35.5 % , respectively , were recorded . The abstinence outcome measures ( pooled 1-year abstinence prevalence = 30.9 % ) were not significantly different between the two preparation strategies . Trends in nicotine and CO exposure drops , and abstinence outcome measures , however , were consistently in favor of the graduated filters . Potential advantages of filters in the context of a preparation-for-quitting strategy were suggested Two theoretical approaches to smoking cessation were compared . Participants were r and omly assigned either to ( a ) a traditional treatment program that used contingency contracting and that emphasized the necessity for absolute abstinence ( AA ) or to ( b ) a relapse-prevention ( RP ) treatment that focused on gradual acquisition of nonsmoking skills . It was hypothesized that participants in the RP treatment would be less successful initially but would have better maintenance skills and thus would relapse less during a 1-year follow-up period . Each program was evaluated in two formats : group-based treatment and self-help material s. Results indicated comparable 1-year abstinence rates for all treatments , although more participants dropped out of the self-help formats . Participants in the RP intervention were more likely to lapse sooner after quitting and were more likely to quit again during the 1-year maintenance period . Exploratory analyses of successful participants suggested that women were more successful in the RP program and that men had greater success with the AA approach Smokers ( N = 99 ) were r and omly assigned to one of three conditions : nicotine gum ( NG ) , nicotine gum plus psychological treatment ( NG-PT ) , and nicotine gum plus psychological treatment and partner support ( NG-PT-PS ) . Data were collected at Weeks 0 , 4 , 12 , 26 , and 52 from study start . Contrary to expectations , NG-PT-PS and NG-PT failed to increase abstinence rates . Subjects who were closer to their support partners had significantly lower abstinence rates with NG-PT-PS than with the other conditions , although not significantly at Weeks 26 and 52 . Treatments without partner participation ( NG-PT and NG ) were significantly more effective for subjects who had an extremely close support partner outside the treatment setting than for those who did not at all weeks . The role of social support in smoking treatment is discussed We compared the relative effectiveness of four different conditions of self-help and social support provided to people attempting to quit smoking in conjunction with a televised cessation program : Smokers ready to quit were able to request written manuals from hardware stores to accompany a televised program . At worksites we provided the written manual to all workers . At a r and om half of the worksites , we also provided training to discussion leaders who subsequently led discussion s among smokers attempting to quit with the program . At health maintenance organization sites we invited smokers who had requested program material s to participate in similar group discussion s at health centers . In this paper we report one year follow-up results for the above four groups and compare them with previously reported results of a self-help manual alone . Results for the television plus manual condition were better than those of past studies ( 25 percent nonsmoking prevalence and 10 percent continuous cessation one year after the program ) and considerably better than the manual alone . None of the other conditions design ed to supplement the manual plus television produced better long-term outcomes ; we explore the reasons for this . The program did encourage and help over 50,000 Chicago smokers to attempt quitting with the American Lung Association manual , 100 times as many as would have done so without the televised program . At least 15 other similar programs implemented since 1984 multiply this effect PURPOSE Patients who continue to smoke following coronary artery bypass graft surgery ( CABG ) have substantially poorer outcomes than patients able to stop smoking after CABG . This study evaluated the effectiveness of two smoking cessation treatment strategies in patients undergoing CABG . METHODS Two smoking cessation treatment strategies were compared in smokers who underwent CABG . In the conservative treatment strategy , smokers undergoing CABG were followed up prospect ively at monthly intervals . Patients who started smoking again at any time in the year following CABG were asked to enroll in an 8-week smoking cessation program . In the aggressive treatment strategy , smokers undergoing CABG were asked to enroll in an 8-week smoking cessation program starting immediately after hospital discharge . The structure and makeup of the smoking cessation program used in the conservative and aggressive treatment strategies were identical . The primary study outcome was smoking status assessed by self-report and confirmed by expired carbon monoxide at 1.5 months , 3 months , 6 months , and 12 months after surgery . RESULTS Nineteen patients were enrolled in the conservative treatment strategy , with 2 patients unavailable for follow-up prior to the first follow-up visit . Of the remaining 17 patients , 14 patients ( 82 % ) resumed smoking at an average of 10.3 weeks after CABG . Eleven of these 14 patients ( 79 % ) agreed to participate in the smoking cessation program . Based on evaluable patients , 10 of the 17 patients ( 59 % ) in the conservative strategy group were not smoking at the 12-month follow-up . Twenty patients were enrolled in the aggressive treatment strategy . All patients agreed to participate in the smoking cessation program . All patients were available for follow-up . At the 12-month follow-up , 17 of 29 patients ( 85 % ) in this treatment strategy were not smoking . Point prevalence and continuous abstinence cessation rates were significantly greater in the aggressive treatment strategy compared to the conservative treatment strategy at all follow-up intervals after CABG . CONCLUSION Based on our findings in a small number of patients , an aggressive smoking cessation intervention is associated with a superior smoking cessation rate compared to a conservative treatment strategy in smokers undergoing CABG . A larger study will be needed to confirm that an early aggressive smoking cessation intervention should be provided to all smokers undergoing CABG Abstract This study evaluated the efficacy of a multiple treatment smoking cessation program and three maintenance strategies . Phase I of the study involved 51 subjects who participated in a 5-day smoking cessation project . The program consisted of lectures , demonstrations , practice exercises , aversive smoking , and the teaching of self-control procedures . In Phase II , all subjects were r and omly assigned to one of three maintenance conditions : a 4-week support group which offered an opportunity to discuss feelings and thoughts , a 4-week telephone contact system which enabled group members to call one another , and a no-contact control group . To evaluate efficacy , extensive follow-up data were collected at the end of treatment and at 2 , 4 , 6 , and 12 months post-treatment . The treatment program was extremely effective ; 100 % of the subjects were abstinent at the end of treatment , and at 1 year post-treatment , 63 % of the subjects reported total abstinence . As to sex differences , at the 1-year period 66 % of the women and 59 % of the men were ex-smokers . Recidivists reported a smoking rate that was 52 % of baseline at the 6-month follow-up . At 2 months post-treatment , 40 % of the abstainers reported that the quitting experience was easy , and subjects reported an average weight gain of only 4.69 lb . The authors offer suggestions for future smoking cessation research based upon the promising findings of this study Cigarette smokers with past major depressive disorder ( MDD ) received 8 group sessions of st and ard , cognitive-behavioral smoking cessation treatment ( ST ; n = 93 ) or st and ard , cognitive-behavioral smokiig cessation treatment plus cognitive-behavioral treatment for depression ( CBT-D ; n = 86 ) . Although abstinence rates were high in both conditions ( ST , 24.7 % ; CBT-D , 32.5 % , at 1 year ) for these nonpharmacological treatments , no main effect of treatment was found . However , secondary analyses revealed significant interactions between treatment condition and both recurrent depression history and heavy smoking ( > or = 25 cigarettes a day ) at baseline . Smokers with recurrent MDD and heavy smokers who received CBT-D were significantly more likely to be abstinent than those receiving ST ( odds ratios = 2.3 and 2.6 , respectively ) . Results suggest that CBT-D provides specific benefits for some , but not all , smokers with a history of MDD Sixty-three companies in the Chicago area were recruited to participate in a worksite smoking cessation program . Participants in each worksite received a television program and newspaper supplement ( part of a community-wide media campaign ) , and one of three conditions : ( 1 ) self-help manuals alone ( M ) , ( 2 ) self-help manuals and incentives for 6 months ( IM ) or ( 3 ) maintenance manuals , incentives and cognitive-behavioral support groups for 6 months ( GIM ) . Results at the 2 year assessment are examined using a r and om-effects regression model . In addition , various definitions of quit-rate commonly used in smoking cessation research are explored and the advantages of using a public health approach in the worksite are examined Abstract A smoking withdrawal clinic procedure employing social pressure was compared to an attention placebo condition and other control conditions design ed to subtract “ non-active ” variance due to such factors as mere contact with an experimenter and individual effort , with and without the expectation of future help . Both Social Pressure and Placebo S s responded to treatment with significant reduction in smoking , but did not differ . Subjects asked to quit smoking on their own , displayed significant gains only if future aid was not expected , and the behavior of subjects who were unaware of their participation in an experiment remained essentially unchanged . Data on suggestibility , internal vs. external control of reinforcement , extroversion and emotionality were collected in Experiment 3 , but failed to correlate significantly ( within treatment conditions ) with success in quitting smoking In the current study , 34 smokers were treated in a smoking cessation program that involved either a scheduled smoking procedure , or a minimal contact self-help treatment control . The interval smoking program consisted of baseline , cessation , and relapse prevention phases . During baseline , subjects self-monitored smoking and the total hours spent awake . During a 3-week cessation period , the scheduled smoking group progressively increased their intercigarette interval , thereby gradually reducing their total daily intake of nicotine . Smokers were expected to quit on a target date set at the end of this period . Cognitive behavioral interventions and relapse prevention training consisted of behavioral rehearsal of nonsmoking skills in a relapse prone environment . Control subjects were given the American Cancer Society " I Quit Kit " , and provided subsequent discussion of its use . The results showed that 53 % and 41 % of the scheduled smoking group was abstinent at the 6- and 12-month follow-up points , respectively . Controls averaged only 6 % for the same periods . Scheduled smoking may be a useful addition to a multicomponent treatment program and further study appears warranted to determine the saliency of the treatment features Aims : Potential exists for improving the impact of quit-smoking programmes , by recruiting smokers in early motivational stages , by using active recruitment strategies , and by offering professional assistance to quit . Methods : This was a r and omized population -based intervention study , in Copenhagen , Denmark . A total of 2,408 daily smokers in all motivational stages were included . All participants completed a question naire , and underwent a health examination and a lifestyle consultation . Smokers in the high-intensity intervention were offered assistance to quit smoking in smoking cessation groups . Results : Before the lifestyle consultation only 11 % of the smokers stated that they planned to quit within one month . After the lifestyle consultation 27 % accepted smoking cessation in groups and an additional 12 % planned to quit without assistance . Of the smokers who accepted smoking cessation groups 23 % had not been planning to quit before the lifestyle consultation . Being a woman , having high tobacco consumption , having a long smoking history , having tried to quit within the previous year , and having a higher motivation to quit predicted participation in smoking cessation groups . Conclusions : It was possible to recruit a large number of smokers in early motivational stages by using active recruitment strategies and by offering assistance to quit . Lifestyle consultations markedly increased the number of smokers willing to try to quit . Smokers preferred assistance to quit in a smoking cessation group to quitting on their own ; therefore , it is important to improve recruitment strategies for smoking cessation programmes AIMS This paper sets out to evaluate the possibility that smoking cessation interventions which make use of current psychological theories and constructs can be more successful than programmes based largely on nicotine replacement therapy and will be more satisfying to participants . RATIONALE Nicotine replacement therapy is currently the most widely used method for helping smokers give up the habit . Numerous studies have shown this to be a successful approach for many smokers , but the majority still fail to benefit . Typically three quarters of smokers given nicotine replacement are smoking again one year later . This study investigates whether nicotine replacement can be enhanced by the addition of psychological techniques . DESIGN Smokers recruited via publicity in the local media were r and omly assigned to one of two treatment conditions . The first condition consisted of a series of group sessions in which volunteers were instructed in nicotine replacement , and a number of psychological techniques , the most important being cognitive counter conditioning . The second condition was identical to the first but without the cognitive counter conditioning . Finally background quit rate was determined using waiting list controls . RESULTS Both interventions were successful in helping smokers quit the habit , based upon an analysis at 6 months , compared with waiting list controls . The experimental condition incorporating cognitive counter conditioning produced a much higher quit rate than the condition based largely upon nicotine replacement , although the difference was not significant . CONCLUSIONS This study is highly suggestive that nicotine replacement therapy can be enhanced by the inclusion of psychological techniques in group work , result ing in abstention rates higher than nicotine replacement alone and increasing participant satisfaction . Further work is needed with larger numbers to verify that this is indeed a significant gain and to investigate whether psychological techniques can give longer term benefits OBJECTIVE Alcohol dependence and major depression have been associated with heavy cigarette use and poor smoking-treatment outcomes . This preliminary study examined the efficacy of a mood management intervention for smoking cessation in abstinent alcoholics with a history of major depression . METHOD Participants were 29 ( 15 female , 14 male ) heavy smokers ( mean cigs/day = 30.2 ) , with an average of 6.8 years of continuous abstinence from alcohol and drugs , r and omized to behavioral counseling ( BC ) ( n = 16 ) or behavioral counseling + cognitive-behavioral mood management ( CBT ) ( n = 13 ) . A 2 x 5 repeated measures design was used to evaluate the effectiveness of the interventions on smoking outcome at baseline , posttreatment and at 1- , 3- and 12-month-follow-up . Self-reported smoking status was verified with biochemical ( COa ) and informant report . RESULTS Verified self-report indicated that significantly more smokers in CBT quit by posttreatment ( 69.2 % ; 9 of 13 ) than in BC ( 31.3 % ; 5 of 16 ) ( chi2 = 4.14 , 1 df , p = .04 ) . These abstinence rates remained unchanged at 1-month follow-up . At 3-month follow-up , differences in smoking abstinence rates were nonsignificant between CBT ( 46.2 % ; 6 of 13 ) and BC ( 25.0 % ; 4 of 16 ) conditions . However , at 12-month follow-up , significantly more participants in CBT were abstinent from smoking ( 46.2 % ; 6 of 13 ) than in BC ( 12.5 % ; 2 of 16 ) ( chi2 = 4.07 , 1 df , p = .04 ) . CONCLUSIONS The results suggest that interventions focused on managing negative mood may benefit these high-risk , comorbid smokers This study examined the effect of depressive symptoms on smoking abstinence and treatment adherence among smokers with a past history of alcohol dependence . Participants ( 24 women , 27 men ) were r and omly assigned to behavioral counseling ( BC ) or behavioral counseling plus cognitive-behavioral mood management training ( CBT ) . The Hamilton Rating Scale for Depression ( HRSD ; M. Hamilton , 1967 ) was administered to assess baseline depressive symptoms . Participants who received CBT and had higher HRSD scores were more likely to achieve short-term abstinence from smoking and attend more treatment sessions than those with lower depression scores , whereas for BC participants the effect of HRSD scores was the opposite . Smokers with a history of alcohol dependence reporting high levels of depressive symptoms may benefit from a mood management intervention BACKGROUND In a population -based sample of smokers in early motivational stages , we found a high acceptance of smoking cessation groups . METHODS Inter99 is a r and omized population -based intervention study , in Copenhagen , Denmark . Smokers in all motivational stages were included . All participants underwent a lifestyle consultation and 2,168 smokers in the high intensity intervention group were offered assistance to quit in smoking cessation groups . RESULTS Thirty-five percent were vali date d to be continuously abstinent at the end of the smoking cessation groups . Eighty-four percent of the smokers achieving sustained abstinence in our study had no serious plans to quit soon before the lifestyle consultation . Motivation to quit before the lifestyle consultation could not predict abstinence . Being a man , and having a job and at least 1 year of vocational training were predictors of abstinence in a multivariate model , whereas high nicotine dependence and living with a smoking spouse were predictors of failure . CONCLUSION High cessation rates were obtained in a population of heavy smokers with moderate nicotine dependence . It was possible to obtain sustained abstinence in smokers in early motivational stages . These smokers would probably not have been reached by traditional smoking campaigns 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 The present investigation undertook a large-scale replication of an apparently successful group cohesion manipulation reported by Etringer , Gregory , and L and o (1984)l A 2 x 2 factorial design was initiated in which subjects were to be r and omly assigned to enriched or st and ard cohesion and to satiation or nicotine fading . However , subject resistance to the satiation technique necessitated the ab and oning of this part of the experimental procedure . Subjects assigned to nicotine fading ( enriched or st and ard cohesion ) included 184 women and 169 men . In contrast to the Etringer et al. study , there was virtually no evidence of a treatment effect on either group cohesion scores or abstinence outcome . Future work might attempt to establish more powerful manipulations of cohesion , which could then be applied especially to groups that fail to coalesce on their own Abstract Five hundred and fifty-eight cigarette smokers ( mean 31 cigarettes/day ) were r and omized in four groups : Acupuncture , Behaviour Therapy , Placebo Medication and Waiting-list Control . The life-table analysis of smoking cessation showed , at a 12-month follow-up , no difference between Acupuncture , Behaviour Therapy and Placebo . Differences appeared only in an analysis of the abstinent subjects at each data point . Behaviour Therapy and Acupuncture accounted for significantly more abstinent subjects than Placebo at the end of the 2-week therapeutic phase . However at 9 and 12 months Acupuncture had a statistically-significant greater number of abstinent subjects than Behaviour Therapy , but there was no difference between Acupuncture and Placebo . The percentage decrease in smoking from baseline appeared significantly greater at 12 months in the first three groups than in the Control conditions . However , as in most smoking-cessation studies , the overall effect was small and non-specific . The results reflect the importance of maintenance programmes and of the prevention of addiction Abstract This study compared two self-management approaches to reduce cigarette smoking . The first was Azrin and Nunn 's habit reversal . The second ( which contained elements of the first ) was based on suggestions of Mahoney et al . for treating obesity . Unlike the habit reversal group , clients in this group were instructed to use self-instructional and self-reinforcement techniques . A third group was also used , one that was modeled after conventional patient education approaches . Each of the groups showed a reduction from baseline smoking during the four month study . However there were no differences between the groups during or at the end of the study . Although the results did not favor any one of the three groups in particular , they suggest that fairly rapid , and in some cases permanent reductions in steady-state smoking are possible without resorting to aversive ( and potentially harmful ) methods such as rapid smoking This study involved 137 participants who were assessed on 12 relevant predictor variables and then r and omly assigned to social support or self-control treatment . Outcome across treatments was predicted by cotinine levels , treatment history , previous abstinence , happiness , self-efficacy , and perceived social support for quitting . Social support treatment was more effective than self-control treatment for participants with high baseline self-control orientation scores and participants with high self-efficacy scores . All other hypothesized Subject x Treatment interaction effects were nonsignificant . The study provided an example of a coherent approach to matching research and demonstrated the difficulty involved in providing treatments that are different enough from each other to benefit different smokers . Matching research has important theoretical value but may have limited potential for improving smoking treatment effectiveness We compared the effectiveness of American Cancer Society , FreshStart , American Lung Association , Freedom from Smoking , and laboratory clinic methods in subjects ( N = 1041 ) from three communities . Three-month follow-up results favored the laboratory method over the two public service approaches on both a prevalence and a sustained abstinence measure . At one-year follow-up , treatment effects for smoking prevalence were no longer significant . However , sustained abstinence results at one-year remained highly significant and favored the more intensive laboratory and Freedom from Smoking clinics over the FreshStart method . FreshStart fared less well than the other interventions both in producing initial quit attempts and in sustaining abstinence among initial quitters . It should be noted , however , that FreshStart requires considerably less facilitator contact than do the other approaches . Unexpected outcome effects occurred for treatment location . Future clinic programs should include a specific target date for quitting and should place more emphasis upon recycling participants who fail to sustain abstinence 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 OBJECTIVES To evaluate the efficacy of a structured behaviour therapy programme on smoking cessation in diabetic patients . DESIGN Prospect i ve , r and omized , controlled intervention study . SETTING University out-patient diabetes clinic . SUBJECTS A total of 794 consecutive insulin-treated smoking diabetic patients were invited to participate in a smoking cessation programme . Eighty-nine patients agreed to participate and were r and omized in two groups . INTERVENTIONS Forty-four patients were r and omized to a structured extensive behaviour therapy anti-smoking intervention and 45 patients to a control group that received a single unstructured anti-smoking advice session given by a physician . MAIN OUTCOME MEASURES After 6 months , nine patients were confirmed not to be smoking ( i.e. urine cotinine concentration below 20 ng ml-1 , 2 [ 5 % ] in the behaviour therapy intervention group and 7 [ 16 % ] in the control group . CONCLUSIONS In diabetic patients an extensive behaviour therapy intervention for smoking cessation is no more successful than an unstructured physician 's advice Purpose . The purpose of this study was to compare a culturally specific , multicomponent behavioral smoking cessation program for Hispanic smokers with a low-intensity , enhanced self-help control condition . Design . Participants who completed pretreatment assessment were r and omly assigned to treatment conditions . Smoking status was evaluated at posttreatment , 6-month follow-up , and 12-month follow-up intervals . Setting . The study was based in predominantly Hispanic neighborhoods in Queens , New York . Participants . Ninety-three Hispanic smokers participated : 48 men and 45 women . Intervention . The multicomponent treatment involved a clinic-based group program that incorporated a culturally specific component consisting of videotaped presentations of culturally laden smoking-related vignettes . The self-help control program was enhanced by the use of an introductory group session and follow-up supportive telephone calls . Measures . Smoking outcomes were based on cotinine-vali date d abstinence and self-reported smoking rates . Predictors of abstinence were examined , including sociodemographic variables , smoking history , nicotine dependence , acculturation , partner interactions , reasons for quitting , self-efficacy , and linguistic competence . Results . Significant group differences in cotinine-vali date d abstinence rates in favor of the multicomponent group were obtained , but only at posttreatment . With missing data included and coded for nonabstinence , vali date d abstinence rates at posttreatment were 21 % for the multicomponent group and 6 % for the self-help group . At the 6-month follow-up , the rates were 13 % for the multicomponent group and 9 % for the self-help group . By the 12-month follow-up , the rates declined to 8 % and 7 % for the multicomponent and self-help groups , respectively . A dose-response relationship between attendance at group sessions and abstinence status was shown at posttreatment and 6-month follow-up intervals . Conclusions . The results of the present study failed to show any long-term benefit from use of a clinic-based , culturally specific multicomponent smoking cessation intervention for Hispanic smokers relative to a minimal-contact , enhanced self-help control Purpose . To determine whether a stress management ( SM ) program could improve cessation rates when added to usual care ( UC ) among women attempting to quit smoking . Design . R and omized controlled trial conducted during a 12-month period . Setting . Smoking cessation clinics located within two tertiary care centers in Ottawa , Ontario . Subjects . A total of 332 women smokers 19 years or older who smoked 10 or more cigarettes per day were recruited via advertisements . Intervention . Either UC ( physician advice and nicotine replacement therapy ) or UC plus an eight-session group SM training program ( coping skills development relevant to smoking-specific and generic stressors ) . Measures . Point prevalence abstinence 2 and 12 months after study intake . A secondary outcome of interest was change in perceived stress during the intervention period . Results . On an intent-to-treat basis , the addition of SM to UC had no incremental effect on 2-or 12-month abstinence rates . Abstinence rates at 2 months were 26.2 % vs. 31.7 % in the UC and SM groups , respectively ( p = .59 ) . At 12 months , the rates were 18.5 % vs. 20.7 % ( p = .86 ) . When quit rates were compared including only participants who demonstrated adequate adherence to the intervention protocol , there was a significant difference between the UC and SM groups at 2 months ( 34.9 % vs. 48.7 % ; adjusted odds ratio , 1.88 ; 95 % confidence interval , 1.04–3.42 ; p = .04 ) but not at 12 months ( 23.0 % vs. 28.2 % ; adjusted odds ratio , 1.24 ; 95 % confidence interval , .64–2.41 ; p = .53 ) . There was a significant reduction in perceived stress from preintervention to postintervention ; however , this decrease was not moderated by group assignment . Conclusion . The addition of SM in our setting neither increased abstinence rates nor reduced perceived stress over and above UC in women motivated to quit smoking . Poor attendance at the SM intervention undermined its effectiveness |
1,291 | 30,077,181 | Conclusions PLT storage time does not appear to be associated with clinical outcomes , including bleeding , sepsis or mortality , in critically ill patients or haematology patients .
The freshest PLTs ( less than 3 days ) were associated with a better CCI , although there was no impact on bleeding events , question ing the clinical significance of this association .
However , there is an absence of evidence to draw definitive conclusions , especially in critically ill patients | Background Platelets ( PLTs ) are usually stored for up to 5 days prior to transfusion , although in some blood services the storage period is extended to 7 days .
During storage , changes occur in both PLT and storage medium , which may lead to PLT activation and dysfunction .
The clinical significance of these changes remains uncertain .
Methods We performed a systematic review to assess the association between PLT storage time and clinical or transfusion outcomes in patients receiving allogeneic PLT transfusion . | A variety of patient and product-related factors influenced the outcome of 6379 transfusions given to 533 patients in the Trial to Reduce Alloimmunization to Platelets ( TRAP ) . Responses measured were platelet increments , interval between platelet transfusions , and platelet refractoriness . Patient factors that improved platelet responses were splenectomy and increasing patient age . In contrast , at least 2 prior pregnancies , male gender , splenomegaly , bleeding , fever , infection , disseminated intravascular coagulation , increasing height and weight , lymphocytotoxic antibody positivity , an increasing number of platelet transfusions , or receiving heparin or amphotericin were associated with decreased posttransfusion platelet responses . Platelet factors that were associated with improved platelet responses were giving ABO-compatible platelets , platelets stored for 48 hours or less , and giving large doses of platelets while ultraviolet B ( UV-B ) or gamma irradiation decreased platelet responses . However , in alloimmunized lymphocytoxic antibody-positive patients , the immediate increment to UV-B-irradiated platelets was well maintained , whereas all other products showed substantial reductions . Refractoriness to platelet transfusions developed in 27 % of the patients . Platelet refractoriness was associated with lymphocytotoxic antibody positivity , heparin administration , fever , bleeding , increasing number of platelet transfusions , increasing weight , at least 2 pregnancies , and male gender . The only factors that reduced platelet refractoriness rates were increasing the dose of platelets transfused or transfusing filtered apheresis platelets BACKGROUND The storage duration of platelet ( PLT ) units is limited to 5 to 7 days . This study investigates whether PLT storage duration is associated with patient outcomes in critically ill patients . STUDY DESIGN AND METHODS This study was a retrospective analysis of critically ill patients admitted to the intensive care unit ( ICU ) of two hospitals in Australia who received one or more PLT transfusions from 2008 to 2014 . Storage duration was approached in several different ways . Outcome variables were hospital mortality and ICU-acquired infection . Associations between PLT storage duration and outcomes were evaluated using multiple logistic regression and also by Cox regression . RESULTS Among 2250 patients who received one or more PLT transfusions while in the ICU , the storage duration of PLTs was available for 64 % of patients ( 1430 ) . In-hospital mortality was 22.1 % and ICU infection rate 7.2 % . When comparing patients who received PLTs of a maximum storage duration of not more than 3 , 4 , or 5 days , there were no significant differences in baseline characteristics . After confounders were adjusted for , the storage duration of PLTs was not independently associated with mortality ( 4 days vs. ≤3 days , odds ratio [ OR ] 0.88 , 95 % confidence interval [ CI ] 0.59 - 1.30 ; 5 days vs. ≤3 days , OR 0.97 , 95 % CI 0.68 - 1.37 ) or infection ( 4 days vs. ≤3 days , OR 0.71 , 95 % CI 0.39 - 1.29 ; 5 days vs. ≤3 days , OR 1.11 , 95 % CI 0.67 - 1.83 ) . Similar results were obtained regardless of how storage duration of PLTs was approached . CONCLUSIONS In this large observational study in a heterogeneous ICU population , storage duration of PLTs was not associated with an increased risk of mortality or infection Pathogen reduction ( PR ) of platelet products increases costs and available clinical studies are equivocal with respect to clinical and haemostatic effectiveness . We conducted a multicentre , open‐label , r and omized , non‐inferiority trial comparing the clinical effectiveness of buffy‐coat derived leucoreduced platelet concentrates ( PC ) stored for up to 7 d in plasma with platelets stored in platelet additive solution III ( PASIII ) without and with treatment with amotosalen‐HCl/ultraviolet‐A ( UVA ) photochemical pathogen reduction ( PR‐PASIII ) . Primary endpoint of the study was 1‐h corrected count increment ( CCI ) . Secondary endpoints were 24‐h CCI , bleeding , transfusion requirement of red cells and PC , platelet transfusion interval and adverse transfusion reactions . Compared to plasma‐PC , in the intention to treat analysis of 278 evaluable patients the mean difference for the 1‐h CCI of PR‐PASIII‐PC and PASIII‐PC was −31 % ( P < 0·0001 ) and −9 % ( P = n.s . ) , respectively . Twenty‐seven patients ( 32 % ) had bleeding events in the PR‐PASIII arm , as compared to 19 ( 19 % ) in the plasma arm and 14 ( 15 % ) in the PASIII arm ( P = 0·034 ) . Despite the potential advantages of pathogen ( and leucocyte ) inactivation of amotosalen‐HCl/UVA‐treated platelet products , their clinical efficacy is inferior to platelets stored in plasma , warranting a critical re appraisal of employing this technique for clinical use BACKGROUND Bacterial screening offers the possibility of extending platelet ( PLT ) storage to Day 7 . We conducted a noninferiority , crossover trial comparing PLTs stored for 6 or 7 days versus 2 to 5 days . STUDY DESIGN AND METHODS Stable hematology patients were allocated to receive blocks of 2- to 5- and 6- or 7-day PLTs in r and om order . The primary outcome was the proportion of successful transfusions during the first block , defined as a corrected count increment ( CCI ) of more than 4.5 at 8 to 24 hours posttransfusion . RESULTS Of 122 patients with an evaluable first block , 87 ( 71 % ) and 84 ( 69 % ) had successful transfusions after 2- to 5- and 6- or 7-day PLTs of mean ( SD ) ages of 3.8 ( 1.0 ) and 6.4 ( 0.5 ) days , respectively . Six- or 7-day PLTs were declared noninferior to 2- to 5-day PLTs since the upper confidence interval ( CI ) limit was less than the predefined noninferiority margin of 10 % ( 95 % CI , -14.0 % to 9.1 % ; p = 0.766 ) . Logistic regression analysis gave an adjusted odds ratio of 0.86 ( 95 % CI , 0.47 - 1.58 ; p = 0.625 ) . Mean ( SD ) 8- to 24-hour CCIs were 9.4 ( 7.9 ) and 7.7 ( 7.1 ) after transfusion with 2- to 5- or 6- or 7-day PLTs ( 95 % CI , -3.31 to 0.03 ; p = 0.054 ) . The proportions of days with bleeding scores of WHO Grade 2 or higher were 13 % ( 38/297 days ) and 11 % ( 32/296 days ; 95 % CI , -3.2 to 7.2 ; p = 0.454 ) . Median interval to next PLT transfusion ( 2 days ) was unaffected ( 95 % CI , -10.5 to 5.4 ; p = 0.531 ) . CONCLUSION In hematology patients , there was no evidence that 6- or 7-day PLTs were inferior to 2- to 5-day PLTs , as measured by proportion of patients with successful transfusions , bleeding events , or interval to next transfusion BACKGROUND Blood transfusion increases the risk of nosocomial infection in trauma patients . Specific patient- and transfusion-related risk factors are largely unknown . In this study , risk factors for developing a bacterial infection after transfusion of red blood cells ( RBC ) or platelets were determined in a cohort of transfused critically ill trauma patients . MATERIAL AND METHODS A retrospective study was conducted in a mixed medical-surgical Intensive Care Unit ( ICU ) of a level-1 university trauma centre , in trauma patients who received a RBC or platelet transfusion . Patients who developed a bacterial infection after transfusion were compared to transfused controls who did not develop such an infection . Multivariable logistic regression was used to determine risk factors for infection . RESULTS Of the 7,118 patients admitted to the ICU during the study period , 196 trauma patients met the inclusion criteria . An infection developed in 56 patients ( 29 % ) . Infection occurred irrespective of the administration of antibiotics as part of selective digestive tract decontamination , surgery status or Injury Severity Score . Transfusion of RBC stored for more than 14 days was associated with infection in trauma patients ( odds ratio 1.038 , [ 95 % CI : 1.01 - 1.07 ] , p=0.036 ) . Neither the amount of RBC nor that of platelets was associated with onset of infection . CONCLUSIONS Transfusion of RBC stored for more then 14 days is a risk factor for onset of bacterial infection after trauma , irrespective of the use of prophylactic antibiotics . Transfusion of platelets was not a risk factor . These results may contribute to design ing prospect i ve studies on transfusion of fresh RBC only in trauma patients Non-r and omised studies of the effects of interventions are critical to many areas of healthcare evaluation , but their results may be biased . It is therefore important to underst and and appraise their strengths and weaknesses . We developed ROBINS-I ( “ Risk Of Bias In Non-r and omised Studies - of Interventions ” ) , a new tool for evaluating risk of bias in estimates of the comparative effectiveness ( harm or benefit ) of interventions from studies that did not use r and omisation to allocate units ( individuals or clusters of individuals ) to comparison groups . The tool will be particularly useful to those undertaking systematic review s that include non-r and omised studies A nucleic acid-targeted photochemical treatment ( PCT ) using amotosalen HCl ( S-59 ) and ultraviolet A ( UVA ) light was developed to inactivate viruses , bacteria , protozoa , and leukocytes in platelet components . We conducted a controlled , r and omized , double-blinded trial in thrombocytopenic patients requiring repeated platelet transfusions for up to 56 days of support to evaluate the therapeutic efficacy and safety of platelet components prepared with the buffy coat method using this pathogen inactivation process . A total of 103 patients received one or more transfusions of either PCT test ( 311 transfusions ) or conventional reference ( 256 transfusions ) pooled , leukoreduced platelet components stored for up to 5 days before transfusion . More than 50 % of the PCT platelet components were stored for 4 to 5 days prior to transfusion . The mean 1-hour corrected count increment for up to the first 8 test and reference transfusions was not statistically significantly different between treatment groups ( 13,100 + /- 5400 vs 14,900 + /- 6200 , P = .11 ) . By longitudinal regression analysis for all transfusions , equal doses of test and reference components did not differ significantly with respect to the 1-hour ( 95 % confidence interval [ CI ] , -3.1 to 6.1 x 10(9)/L , P = .53 ) and 24-hour ( 95 % CI , -1.3 to 6.5 x 10(9)/L , P = .19 ) posttransfusion platelet count . Platelet transfusion dose , pretransfusion storage duration , and patient size were significant covariates ( P < .001 ) for posttransfusion platelet counts . Clinical hemostasis , hemorrhagic adverse events , and overall adverse events were not different between the treatment groups . Platelet components prepared with PCT offer the potential to further improve the safety of platelet transfusion using technology compatible with current methods to prepare buffy coat platelet components BACKGROUND Studies in cardiac surgery have reported increased postoperative morbidity and mortality after allogeneic red blood cell ( RBC ) transfusions . Whether platelet ( PLT ) and /or plasma transfusions are a marker for more concomitant RBC transfusions or are independently associated with complications after cardiac surgery is unknown . STUDY DESIGN AND METHODS Data from two r and omized controlled studies were combined to analyze the effects of PLT and /or plasma transfusions on postoperative infections , length of stay in the intensive care unit ( ICU ) , all-cause mortality , and mortality in the presence or absence of infections in the postoperative period . RESULTS After adjusting for confounding factors , plasma units and not RBC transfusions were associated with all-cause mortality . White blood cell (WBC)-containing RBC transfusions and PLT transfusions were associated with mortality occurring in the presence of or after infections . The number of ( WBC-containing ) RBC transfusions was also significantly associated with postoperative infections and with ICU stay for 4 or more days . CONCLUSION Although it is difficult to separate the effects of blood components , we found that in cardiac surgery , perioperative plasma transfusions are independently associated with all-cause mortality . WBC-containing RBC transfusions and PLT transfusions are independently associated with mortality in the presence of infections in the postoperative period . Future transfusion studies in cardiac surgery should concomitantly consider the possible adverse effects of all the various transfused blood components BACKGROUND Providing patients with platelet ( PLT ) transfusions requires important logistic re sources and represents a considerable cost factor . Optimizing PLT transfusions is in the interest of not only patient safety but also economic importance . Only few studies have evaluated factors associated with transfusion results . STUDY DESIGN AND METHODS In a prospect i ve single-center study , 9923 mainly prophylactic PLT transfusions given to 672 patients treated for hematologic malignancies between 1997 and 2004 were investigated . Patient and product factors were analyzed . Transfusion efficacy was measured by the corrected count increment ( CCI ) , and side effects were recorded . RESULTS The mean CCI of all transfusions was 14.05 ( st and ard deviation , 9.5 ) . The CCI correlates with the transfusion interval . PLT transfusions that result ed in a transfusion interval of 1 day or less had significantly lower CCI of 11.3 than transfusions that result ed in a transfusion interval of 2 days or more ( 15.57 ) . Allogeneic stem cell transplant recipients had a significantly lower transfusion efficacy ( CCI mean , 13.3 ) whereas patients treated with antithymocyte globulin ( ATG ) had better CCIs ( 17.2 ) compared to patients who were treated with chemotherapy only . Longer PLT storage time and ABO mismatch had a negative impact on transfusion efficacy . PLTs stored in PLT additive storage solution were less effective than PLTs stored in their own autologous plasma . CONCLUSION Manipulation of PLT products may result in lower transfusion efficacy as illustrated by the introduction of PLT additive storage solution in this report . The higher number of products used per patient may negatively impact on advantages gained by the transfusion of " safer " PLT products BACKGROUND Biological response modifiers ( BRMs ) , secreted by platelets ( PLTs ) during storage , play a role in adverse events ( AEs ) associated with transfusion . Moreover , mitochondrial DNA ( mtDNA ) levels in PLT components ( PCs ) are associated with AEs . In this study we explore whether there is a correlation between pathogenic BRMs and mtDNA levels and whether these markers can be considered predictors of transfusion pathology . STUDY DESIGN AND METHODS We investigated a series of reported AEs after PC transfusion , combining clinical observations and mathematical modeling systems . RESULTS mtDNA was consistently released during the first days of PC storage ; however , mtDNA release was earlier in " pathogenic " than in nonpathogenic PCs . PC supernatants with high levels of mtDNA along with soluble CD40 lig and ( sCD40L ) were significantly associated with occurrences of AEs . The fact that mtDNA did not associate with the 14 BRMs tested suggests the role of mtDNA in PC transfusion-linked inflammation is independent of that of BRMs , known to be associated with AEs . We present evidence that PLTs generate distinct pathogenic secretion profiles of BRMs and mtDNA . The calculated area under the curve for mtDNA was significantly associated with AEs , although less stringently predictive than those of sCD40L or interleukin-13 , st and ard predictors of AE . The established model predicts that distinct subtypes of AEs can be distinguished , dependent on mtDNA levels and PC storage length . CONCLUSIONS Further work should be considered to test the propensity of mtDNA in PLT concentrates to generate inflammation and cause an AE OBJECTIVE To evaluate the clinical effect of platelet concentrate ( PC ) transfusions after PC storage time reduction to 4 days . PATIENTS AND METHODS This was a single-centre cohort study comparing two 3-month periods of time , before and after the reduction of PC storage time from 5 to 4 days . Seventy-seven consecutive patients with PC transfusions were enrolled after blood stem cell transplantation . Corrected platelet count increment ( CCI ) on the morning after transfusion , time to next platelet transfusion , need for red blood cell ( RBC ) transfusion and clinical bleeding symptoms were compared . RESULTS Platelet concentrate storage time was reduced between period 1 ( storage for up to 5 days , median storage time 78 h , range 11 - 136 h ) and period 2 ( storage for up to 4 days , median storage time 53 h , range 11 - 112 h ) . Patients were comparable for age , weight , body surface area , underlying disorder , type of transplantation and transfused platelet dose . The CCI increased from a median of 4 ( range 0 - 20 ) to 8 ( 0 - 68 ) × 10(9 ) /l per 10(11 ) platelets/m(2 ) ( P < 0·0001 ) . Time to next PC transfusion increased from 1·1 to 2·0 days ( P < 0·0001 ) . Any bleeding symptom was noted in 20 of 36 patients ( 56 % ) vs. 9/41 patients ( 22 % , P < 0·01 ) . Nose bleeds , haematuria and bleeding at more than one site were significantly reduced . Frequency of RBC transfusion within 5 days after PC transfusion was reduced from 74 to 58 % ( P < 0·0001 ) . CONCLUSION Platelet concentrate storage time shortening was associated with highly significant CCI increase , reduced RC needs and lower patient numbers with bleeding events BACKGROUND AND OBJECTIVES Therapeutic or prophylactic use of platelet concentrates ( PC ) is essential for patients with thrombocytopenia due to intensive chemotherapy for various malignancies . PC quality has been improved after introduction of storage containers that are more oxygen permeable than the second-generation PC containers . Consequently , shelf life of PCs at our blood bank has been extended to 6.5 days after monitoring each PC for bacterial contamination . In this prospect i ve observational study , we compared apheresis PCs harvested by Amicus cell separator with buffy-coat ( BC ) PCs during storage for up to 6.5 days . MATERIAL S AND METHODS All PCs were collected from healthy volunteer donors and were prepared for routine clinical use . A total of 446 transfusion episodes with 688 PCs for 77 adult patients with oncological and haematological diseases were registered during a 13-month period . Outcome measures were corrected count increment after 1 h ( CCI-1 ) , after 18 - 24 h ( CCI-2 ) , and transfusion intervals . Transfusions were carried out after storage from 1.5 to 6.5 days . RESULTS Both CCI and the transfusion intervals decreased statistically significantly by increasing storage time after transfusions with apheresis PCs or BC PCs . However , less than 4 % of the variation in CCI and transfusion interval could be explained by platelet storage time . There were no significant differences between BC PCs and apheresis PCs , regarding CCI and transfusion intervals . CONCLUSION We can conclude that BC PCs are not inferior to apheresis PCs , and may serve the clinical purpose s as well as apheresis PCs harvested by Amicus BACKGROUND We conducted a trial of prophylactic platelet transfusions to evaluate the effect of platelet dose on bleeding in patients with hypoproliferative thrombocytopenia . METHODS We r and omly assigned hospitalized patients undergoing hematopoietic stem-cell transplantation or chemotherapy for hematologic cancers or solid tumors to receive prophylactic platelet transfusions at a low dose , a medium dose , or a high dose ( 1.1x10(11 ) , 2.2x10(11 ) , or 4.4x10(11 ) platelets per square meter of body-surface area , respectively ) , when morning platelet counts were 10,000 per cubic millimeter or lower . Clinical signs of bleeding were assessed daily . The primary end point was bleeding of grade 2 or higher ( as defined on the basis of World Health Organization criteria ) . RESULTS In the 1272 patients who received at least one platelet transfusion , the primary end point was observed in 71 % , 69 % , and 70 % of the patients in the low-dose group , the medium-dose group , and the high-dose group , respectively ( differences were not significant ) . The incidences of higher grade s of bleeding , and other adverse events , were similar among the three groups . The median number of platelets transfused was significantly lower in the low-dose group ( 9.25x10(11 ) ) than in the medium-dose group ( 11.25x10(11 ) ) or the high-dose group ( 19.63x10(11 ) ) ( P=0.002 for low vs. medium , P<0.001 for high vs. low and high vs. medium ) , but the median number of platelet transfusions given was significantly higher in the low-dose group ( five , vs. three in the medium-dose and three in the high-dose group ; P<0.001 for low vs. medium and low vs. high ) . Bleeding occurred on 25 % of the study days on which morning platelet counts were 5000 per cubic millimeter or lower , as compared with 17 % of study days on which platelet counts were 6000 to 80,000 per cubic millimeter ( P<0.001 ) . CONCLUSIONS Low doses of platelets administered as a prophylactic transfusion led to a decreased number of platelets transfused per patient but an increased number of transfusions given . At doses between 1.1x10(11 ) and 4.4x10(11 ) platelets per square meter , the number of platelets in the prophylactic transfusion had no effect on the incidence of bleeding . ( Clinical Trials.gov number , NCT00128713 . Platelet characteristics , such as platelet dose , platelet source ( apheresis vs pooled ) , platelet donor-recipient ABO compatibility , and duration of platelet storage , can affect posttransfusion platelet increments , but it is unclear whether these factors impact platelet transfusion efficacy on clinical bleeding . We performed secondary analyses of platelet transfusions given in the prospect i ve r and omized Platelet Dose Study , which included 1272 platelet-transfused hematology-oncology patients who received 6031 prophylactic platelet transfusions . The primary outcome of these analyses was time from first transfusion to first World Health Organization ≥ grade 2 bleeding . Platelet transfusion increments were assessed at 0.25 to 4 hours and 16 to 32 hours after platelet transfusion . There were 778 patients evaluable for analysis of time to bleeding . Adjusted models showed that r and omized dose strategy , platelet source , ABO compatibility , and duration of storage did not predict this outcome . Platelet increments were generally higher for transfusions of apheresis platelets , ABO-identical platelets , and platelets stored 3 days versus 4 to 5 days . Thus , although platelet source , ABO compatibility , and duration of storage exert a modest impact on both absolute and corrected posttransfusion platelet increments , they have no measurable impact on prevention of clinical bleeding . This trial was registered at www . clinical trials.gov as # NCT00128713 BACKGROUND How platelet ( PLT ) product characteristics such as dose , source ( whole blood derived [ WBD ] vs. apheresis ) , storage duration , and ABO matching status affect the risks of transfusion-related adverse events ( TRAEs ) is unclear . Similarly , more information is needed to define how recipient characteristics affect the frequency of TRAEs after PLT transfusion . STUDY DESIGN AND METHODS In the multicenter Platelet Dose ( " PLADO " ) study , pediatric and adult hematology-oncology patients with hypoproliferative thrombocytopenia were r and omized to receive low-dose ( LD ) , medium-dose ( MD ) , or high-dose ( HD ) PLT prophylaxis for a pretransfusion PLT count of not more than 10 × 10(9 ) /L. All PLT units ( apheresis or WBD ) were leukoreduced . Post hoc analyses of PLADO data were performed using multipredictor models . RESULTS A total of 5034 PLT transfusions to 1102 patients were analyzed . A TRAE occurred with 501 PLT transfusions ( 10.0 % ) . The most common TRAEs were fever ( 6.6 % of transfusions ) , allergic or hypersensitivity reactions ( 1.9 % ) , and sinus tachycardia ( 1.8 % ) . Patients assigned HD PLTs were more likely than LD or MD patients to experience any TRAE ( odds ratio for HD vs. MD , 1.50 ; 95 % confidence interval , 1.10 - 2.05 ; three-group comparison p = 0.02 ) . PLT source and ABO matching status were not significantly related to overall TRAE risk . Compared to a patient 's first PLT transfusion , subsequent PLT transfusions were less likely to have a TRAE reported , primarily due to a lower risk of allergic or hypersensitivity reactions . CONCLUSION The most important PLT unit characteristic associated with TRAEs was PLT dose per transfusion . HD PLTs may increase the risk of TRAEs , and LD PLTs may reduce the risk BACKGROUND AND OBJECTIVE Storage of platelets > 5 days provides improved availability , logistical management and decreased outdating . Promising results on in vitro parameters and on in vivo post-transfusion recovery and survival of autologous platelets in healthy volunteers have earlier been shown . To provide additional verification , r and omized patient transfusion studies are needed . MATERIAL S AND METHODS Sixty allogeneic haematopoietic progenitor cell transplant recipients were r and omized to receive buffy-coat ( BC ) platelets stored in platelet additive solution ( PAS ) for 1 - 5 days the first time a prophylactic transfusion was needed after transplantation , followed the second time by platelets stored for 6 - 7 days or vice versa . The corrected count increment ( CCI ) for 1 and 24 h were calculated . RESULTS CCI 1 h and CCI 24 h were higher for platelets stored 1 - 5 days as compared to 6 - 7 days , 10.4 + /- 5.1 vs. 7.4 + /- 3.8 ( P < 0.001 ) and 5.4 + /- 4.1 vs. 2.6 + /- 2.6 ( P < 0.001 ) , respectively . Time to next platelet transfusion was significantly longer after a transfusion of platelets stored for 1 - 5 days as compared to platelets stored for 6 - 7 days : 2.2 + /- 1.1 vs. 1.6 + /- 0.8 days , respectively ( P < 0.005 ) . No differences in bleeding events and no transfusion reaction were recorded . CONCLUSION The advantage of an extension of platelet storage time beyond day 5 should be balanced against the increased need for platelet transfusions that may occur and the conceivable risk of transfusion failure |
1,292 | 31,250,725 | Conclusion : Non-pharmacological delirium interventions have frequently excluded and under-characterised people requiring palliative care and infrequently reported their outcomes | Background : Delirium is common , distressing , serious and under- research ed in specialist palliative care setting s. Objectives : To examine whether people requiring palliative care were included in non-pharmacological delirium intervention studies in inpatient setting s , how they were characterised and what their outcomes were . | BACKGROUND Hospital-acquired delirium is a known risk factor for negative outcomes in patients admitted to the surgical intensive care unit ( SICU ) . Outcomes worsen as the duration of delirium increases . The purpose of this study was to evaluate the efficacy of a delirium prevention program and determine whether it decreased the incidence and duration of hospital-acquired delirium in older adults ( age>50 y ) admitted to the SICU . METHODS A prospect i ve pre- or post-intervention cohort study was done at an academic level I trauma center . Older adults admitted to the SICU were enrolled in a delirium prevention program . Those with traumatic brain injury , dementia , or 0 d of obtainable delirium status were excluded from analysis . The intervention consisted of multidisciplinary education , a pharmacologic protocol to limit medications associated with delirium , and a nonpharmacologic sleep enhancement protocol . Primary outcomes were incidence of delirium and delirium-free days/30 . Secondary outcomes were ventilator-free days/30 , SICU length of stay ( LOS ) , daily and cumulative doses of opioids ( milligram , morphine equivalents ) and benzodiazepines ( milligram , lorazepam equivalents ) , and time spent in severe pain ( greater than or equal to 6 on a scale of 1 - 10 ) . Delirium was measured using the Confusion Assessment Method for the ICU . Data were analyzed using Chi-squared and Wilcoxon rank sum analysis . RESULTS Of 624 patients admitted to the SICU , 123 met inclusion criteria : 57 preintervention ( 3/12 - 6/12 ) and 66 postintervention ( 7/12 - 3/13 ) . Cohorts were similar in age , gender , ratio of trauma patients , and Injury Severity Score . Postintervention , older adults experienced delirium at the same incidence ( pre 47 % versus 58 % , P=0.26 ) , but for a significantly decreased duration as indicated by an increase in delirium-free days/30 ( pre 24 versus 27 , P=0.002 ) . After intervention , older adults with delirium had more vent-free days ( pre 21 versus 25 , P=0.03 ) , shorter SICU LOS ( pre 13 [ median 12 ] versus 7 [ median 6 ] , P=0.01 ) and were less likely to be treated with benzodiazepines ( pre 85 % versus 63 % , P=0.05 ) with a lower daily dose when prescribed ( pre 5.7 versus 3.6 mg , P=0.04 ) . After intervention , all older adults spent less time in pain ( pre 4.7 versus 3.1 h , P=0.02 ) , received less total opioids ( pre 401 versus 260 mg , P=0.01 ) , and had shorter SICU LOS ( pre 9 [ median 5 ] versus 6 [ median 4 ] , P=0.04 ) . CONCLUSIONS Although delirium prevention continues to be a challenge , this study successfully decreased the duration of delirium for older adults admitted to the SICU . Our simple , cost-effective program led to improved pain and sedation outcomes . Older adults with delirium spent less time on the ventilator and all patients spent less time in the SICU BACKGROUND The objective of this study was to evaluate implementation of an innovative intervention design ed to prevent complications and stimulate early rehabilitation among frail elderly in patients . METHODS The program was implemented in April 2011 . A mixed- methods process evaluation and before-after study were performed . Primary effect outcomes included incidence of hospital-acquired delirium , cognitive decline , and decline in activities of daily living ( ADL ) during hospital stay . Secondary endpoints included ADL performance 3 months postdischarge , readmission , and caregiver burden . RESULTS One hundred ninety-one preintervention and 195 postintervention patients aged 70 years or older were included . Overall , no significant differences in primary endpoints were found . Mean ADL between discharge and follow-up improved ( 3.2 vs 5.7 , P = .058 ) . Caregivers rated burden of care lower at 3 months postdischarge ( .5 vs -.6 , P = .049 ) . CONCLUSIONS The CareWell in Hospital program was implemented satisfactorily . Although the low baseline delirium incidence ( 11 % ) , higher comorbidity , and an increasing learning curve during a restricted implementation period potentially influenced the overall effects , this integrated care program may have beneficial effects on outcomes among frail elderly surgical patients Importance The use of benzodiazepines to control agitation in delirium in the last days of life is controversial . Objective To compare the effect of lorazepam vs placebo as an adjuvant to haloperidol for persistent agitation in patients with delirium in the setting of advanced cancer . Design , Setting , and Participants Single-center , double-blind , parallel-group , r and omized clinical trial conducted at an acute palliative care unit at MD And erson Cancer Center , Texas , enrolling 93 patients with advanced cancer and agitated delirium despite scheduled haloperidol from February 11 , 2014 , to June 30 , 2016 , with data collection completed in October 2016 . Interventions Lorazepam ( 3 mg ) intravenously ( n = 47 ) or placebo ( n = 43 ) in addition to haloperidol ( 2 mg ) intravenously upon the onset of an agitation episode . Main Outcomes and Measures The primary outcome was change in Richmond Agitation-Sedation Scale ( RASS ) score ( range , −5 [ unarousable ] to 4 [ very agitated or combative ] ) from baseline to 8 hours after treatment administration . Secondary end points were rescue neuroleptic use , delirium recall , comfort ( perceived by caregivers and nurses ) , communication capacity , delirium severity , adverse effects , discharge outcomes , and overall survival . Results Among 90 r and omized patients ( mean age , 62 years ; women , 42 [ 47 % ] ) , 58 ( 64 % ) received the study medication and 52 ( 90 % ) completed the trial . Lorazepam + haloperidol result ed in a significantly greater reduction of RASS score at 8 hours ( −4.1 points ) than placebo + haloperidol ( −2.3 points ) ( mean difference , −1.9 points [ 95 % CI , −2.8 to −0.9 ] ; P < .001 ) . The lorazepam + haloperidol group required less median rescue neuroleptics ( 2.0 mg ) than the placebo + haloperidol group ( 4.0 mg ) ( median difference , −1.0 mg [ 95 % CI , −2.0 to 0 ] ; P = .009 ) and was perceived to be more comfortable by both blinded caregivers and nurses ( caregivers : 84 % for the lorazepam + haloperidol group vs 37 % for the placebo + haloperidol group ; mean difference , 47 % [ 95 % CI , 14 % to 73 % ] , P = .007 ; nurses : 77 % for the lorazepam + haloperidol group vs 30 % for the placebo + haloperidol group ; mean difference , 47 % [ 95 % CI , 17 % to 71 % ] , P = .005 ) . No significant between-group differences were found in delirium-related distress and survival . The most common adverse effect was hypokinesia ( 3 patients in the lorazepam + haloperidol group [ 19 % ] and 4 patients in the placebo + haloperidol group [ 27 % ] ) . Conclusions and Relevance In this preliminary trial of hospitalized patients with agitated delirium in the setting of advanced cancer , the addition of lorazepam to haloperidol compared with haloperidol alone result ed in a significantly greater reduction in agitation at 8 hours . Further research is needed to assess generalizability and adverse effects . Trial Registration clinical trials.gov Identifier : OBJECTIVES To determine whether a higher blood transfusion threshold would prevent new or worsening delirium symptoms in the hospital after hip fracture surgery . DESIGN Ancillary study to a r and omized clinical trial . SETTING Thirteen hospitals in the United States and Canada . PARTICIPANTS One hundred thirty-nine individuals hospitalized with hip fracture aged 50 and older ( mean age 81.5 ± 9.1 ) with cardiovascular disease or risk factors and hemoglobin concentrations of less than 10 g/dL within 3 days of surgery recruited in an ancillary study of the Transfusion Trigger Trial for Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair . INTERVENTION Individuals in the liberal treatment group received one unit of packed red blood cells and as much blood as needed to maintain hemoglobin concentrations at greater than 10 g/dL ; those in the restrictive treatment group received transfusions if they developed symptoms of anemia or their hemoglobin fell below 8 g/dL. MEASUREMENTS Delirium assessment s were performed before r and omization and up to three times after r and omization . The primary outcome was severity of delirium according to the Memorial Delirium Assessment Scale ( MDAS ) . The secondary outcome was the presence or absence of delirium defined according to the Confusion Assessment Method ( CAM ) . RESULTS The liberal group received a median two units of blood and the restrictive group zero units of blood . Hemoglobin concentration on Day 1 after r and omization was 1.4 g/dL higher in the liberal group . Treatment groups did not differ significantly at any time point or over time on MDAS delirium severity ( P = .28 ) or CAM delirium presence ( P = .83 ) . CONCLUSION Blood transfusion to maintain hemoglobin concentrations greater than 10 g/dL alone is unlikely to influence delirium severity or rate in individuals with hip fracture after surgery with a hemoglobin concentration less than 10 Introduction This study hypothesised that a reduction of sound during the night using earplugs could be beneficial in the prevention of intensive care delirium . Two research questions were formulated . First , does the use of earplugs during the night reduce the onset of delirium or confusion in the ICU ? Second , does the use of earplugs during the night improve the quality of sleep in the ICU ? Methods A r and omized clinical trial included adult intensive care patients in an intervention group of 69 patients sleeping with earplugs during the night and a control group of 67 patients sleeping without earplugs during the night . The research ers were blinded during data collection . Assignment was performed by an independent nurse research er using a computer program . Eligible patients had an expected length of stay in the ICU of more than 24 hours , were Dutch- or English-speaking and scored a minimum Glasgow Coma Scale of 10 . Delirium was assessed using the vali date d NEECHAM scale , sleep perception was reported by the patient in response to five questions . Results The use of earplugs during the night lowered the incidence of confusion in the studied intensive care patients . A vast improvement was shown by a Hazard Ratio of 0.47 ( 95 % confidence interval ( CI ) 0.27 to 0.82 ) . Also , patients sleeping with earplugs developed confusion later than the patients sleeping without earplugs . After the first night in the ICU , patients sleeping with earplugs reported a better sleep perception . Conclusions Earplugs may be a useful instrument in the prevention of confusion or delirium . The beneficial effects seem to be strongest within 48 hours after admission . The relation between sleep , sound and delirium , however , needs further research .Trial registration Current Controlled Trials IS RCT 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 Background : Major depression is a frequent and serious disorder in older medical in patients . Because the condition goes undetected and untreated in most of these patients , we conducted a r and omized clinical trial to evaluate the effectiveness of a strategy of systematic detection and multidisciplinary treatment of depression in this population . Methods : Consecutive patients aged 65 years or more admitted to general medical services in a primary care hospital between October 1999 and November 2002 were screened for depression with the Diagnostic Interview Schedule ( DIS ) within 48 hours after admission . Patients found to have major depression were r and omly allocated to receive the intervention or usual care . The intervention involved consultation and treatment by a psychiatrist and follow-up by a research nurse and the patient 's family physician . Research assistants , blind to group allocation , collected data from the patients at enrolment and at 3 and 6 months later using the Hamilton Depression Rating Scale ( HAMD ) , the Medical Outcomes 36-item Short Form ( SF-36 ) , the DIS , the Mini-Mental State Examination ( MMSE ) , the Older Americans Re sources and Services ( OARS ) question naire to assess basic and instrumental activities of daily living ( OARS-ADL and OARS-IADL ) and the Rating Scale for Side Effects . Data on the severity of illness , length of hospital stay , health services and medication use , mortality and process of care were also collected . The primary outcome measures were the HAMD and SF-36 . Results : Of 1500 eligible patients who were screened , 157 were found to have major depression and consented to participate ( 78 in the intervention group and 79 in the usual care group ) . At r and omization , there were no clinical ly or statistically significant differences between the 2 groups . Sixty-four patients completed follow-up to 6 months , 57 withdrew , and 36 died . At 6 months , there were no clinical ly or statistically significant differences the 2 groups in HAMD or SF-36 scores or any of the secondary outcome measures . Interpretation : We were unable to demonstrate that systematic detection and multidisciplinary care of depression was more beneficial than usual care for elderly medical in patients OBJECTIVE Delirium is a highly prevalent and deleterious disorder in terminally ill cancer patients . We assessed whether a multicomponent preventive intervention was effective in decreasing delirium incidence and severity among cancer patients receiving end-of-life care . METHODS A cohort of 1516 patients was followed from admission to death at seven Canadian palliative care centers . In two of these centers , routine care included a delirium preventive intervention targeting physicians ( written notice on selective delirium risk factors and inquest on intended medication changes ) , patients , and their family ( orientation to time and place , information about early delirium symptoms ) . Delirium frequency and severity were compared between patients at the intervention ( N = 674 ) and usual-care ( N = 842 ) centers based on thrice-daily symptom assessment s with the Confusion Rating Scale . RESULTS The overall rate of adherence to the intervention was 89.7 % . The incidence of delirium was 49.1 % in the intervention group , compared with 43.9 % in the usual-care group ( odds ratio [ OR ] 1.23 , P = 0.045 ) . When confounding variables were controlled for , no difference was observed between the intervention and the usual-care groups in delirium incidence ( OR 0.94 , P = 0.66 ) , delirium severity ( 1.83 vs. 1.92 ; P = 0.07 ) , total days in delirium ( 4.57 vs. 3.57 days ; P = 0.63 ) , or duration of first delirium episode ( 2.9 vs. 2.1 days ; P = 0.96 ) . Delirium-free survival was similar in the two groups . CONCLUSION A simple multicomponent preventive intervention was ineffective in reducing delirium incidence or severity among cancer patients receiving end-of-life care . Delirium prevention remains a difficult challenge in terminally ill cancer patients OBJECTIVES Delirium ( or acute confusional state ) affects 35 % to 65 % of patients after hip-fracture repair , and has been independently associated with poor functional recovery . We performed a r and omized trial in an orthopedic surgery service at an academic hospital to determine whether proactive geriatrics consultation can reduce delirium after hip fracture . DESIGN Prospect i ve , r and omized , blinded . SETTING Inpatient academic tertiary medical center . PARTICIPANTS 126 consenting patients 65 and older ( mean age 79 + /- 8 years , 79 % women ) admitted emergently for surgical repair of hip fracture . MEASUREMENTS Detailed assessment through interviews with patients and design ated proxies and review of medical records was performed at enrollment to ascertain prefracture status . Subjects were then r and omized to proactive geriatrics consultation , which began preoperatively or within 24 hours of surgery , or " usual care . " A geriatrician made daily visits for the duration of the hospitalization and made targeted recommendations based on a structured protocol . To ascertain study outcomes , all subjects underwent daily , blinded interviews for the duration of their hospitalization , including the Mini-Mental State Examination ( MMSE ) , the Delirium Symptom Interview ( DSI ) , and the Memorial Delirium Assessment Scale ( MDAS ) . Delirium was diagnosed using the Confusion Assessment Method ( CAM ) algorithm . RESULTS The 62 patients r and omized to geriatrics consultation were not significantly different ( P>.1 ) from the 64 usual-care patients in terms of age , gender , prefracture dementia , comorbidity , type of hip fracture , or type of surgical repair . Sixty-one percent of geriatrics consultation patients were seen preoperatively and all were seen within 24 hours postoperatively . A mean of 10 recommendations were made throughout the duration of the hospitalization , with 77 % adherence by the orthopedics team . Delirium occurred in 20 /62 ( 32 % ) intervention patients , versus 32 / 64 ( 50 % ) usual-care patients ( P = .04 ) , representing a relative risk of 0.64 ( 95 % confidence interval ( CI ) = 0.37 - 0.98 ) for the consultation group . One case of delirium was prevented for every 5.6 patients in the geriatrics consultation group . There was an even greater reduction in cases of severe delirium , occurring in 7/ 60 ( 12 % ) of intervention patients and 18 / 62 ( 29 % ) of usual-care patients , with a relative risk of 0.40 ( 95 % CI = 0.18 - 0.89 ) . Despite this reduction in delirium , length of stay did not significantly differ between intervention and usual-care groups ( median + /- interquartile range = 5 + /- 2 days in both groups ) , likely because protocol s and pathways predetermined length of stay . In subgroup analyses , geriatrics consultation was most effective in reducing delirium in patients without prefracture dementia or activities of daily living ( ADL ) functional impairment . CONCLUSIONS Proactive geriatrics consultation was successfully implemented with good adherence after hip-fracture repair . Geriatrics consultation reduced delirium by over one-third , and reduced severe delirium by over one-half . Our trial provides strong preliminary evidence that proactive geriatrics consultation may play an important role in the acute hospital management of hip-fracture patients Objective To determine if a programme of progressive resistance exercise , mobilisation and orientation , in addition to usual care , was superior to usual care alone in the prevention of incident delirium in older hospitalised patients . Design A r and omised controlled trial . Setting The study was performed at a secondary referral hospital in Melbourne , Australia between May 2005 and December 2007 . Participants 648 consecutive medical in patients aged 65 years or older who had been in hospital for less than 48 h and who did not have delirium . Intervention Participants were r and omly allocated to a twice-daily programme of progressive resistance exercise tailored to individual ability , mobilisation and orientation in addition to usual care or to usual care alone . Measurements Delirium was measured using the Confusion Assessment Method at baseline and every 48 h until discharge . Secondary outcome measures were severity and duration of delirium , discharge destination and length of stay . Results Delirium occurred in 4.9 % ( 95 % CI 2.3 % to 7.3 % ) of the intervention group ( 15/305 ) and in 5.9 % ( 20/339 ; 95 % CI 3.8 % to 9.2 % ) of the group receiving usual care . No difference was observed between groups ( χ2 ; p=0.5 ) . The intervention had no effect on delirium duration , severity , discharge destination or length of stay . Conclusion A programme of progressive resistance exercise and orientation was not effective in reducing incident delirium in hospitalised elderly patients BACKGROUND delirium is a clinical syndrome associated with multiple short and long-term complications and therefore prevention is an essential part of its management . This study was design ed to assess the efficacy of multicomponent intervention in delirium prevention . METHODS a total of 287 hospitalised patients at intermediate or high risk of developing delirium were r and omised to receive a non-pharmacological intervention delivered by family members ( 144 patients ) or st and ard management ( 143 patients ) . The primary efficacy outcome was the occurrence of delirium at any time during the course of hospitalisation . Three vali date d observers performed the event adjudication by using the confusion assessment method screening instrument . RESULTS there were no significant differences in the baseline characteristics between the two groups . The primary outcome occurred in 5.6 % of the patients in the intervention group and in 13.3 % of the patients in the control group ( relative risk : 0.41 ; confidence interval : 0.19 - 0.92 ; P = 0.027 ) . CONCLUSION the results of this study show that there is a benefit in the non-pharmacological prevention of delirium using family members , when compared with st and ard management of patients at risk of developing this condition Objective To refine and evaluate a practical , clinical tool to help multidisciplinary teams in the UK and internationally , to identify patients at risk of deteriorating and dying in all care setting s. Methods We used a participatory research approach to refine the 2010 Supportive and Palliative Care Indicators Tool ( SPICT ) and evaluate its use in clinical practice . We conducted an ongoing peer review process for 18 months via an open access webpage , and engaged over 30 clinicians from the UK and internationally in developing an effective tool . Secondly , we carried out a prospect i ve case-finding study in an acute hospital in SE Scotl and . Four multidisciplinary teams identified 130 patients with advanced kidney , liver , cardiac or lung disease following an unplanned hospital admission . Results The SPICT was refined and up date d to consist of readily identifiable , general indicators relevant to patients with any advanced illness , and disease-specific indicators for common advanced conditions . Hospital clinicians used the SPICT to identify patients at risk of deteriorating and dying . Patients who died had significantly more unplanned admissions , persistent symptoms and increased care needs . By 12 months , 62 ( 48 % ) of the identified patients had died . 69 % of them died in hospital , having spent 22 % of their last 6 months there . Conclusions The SPICT can support clinical judgment by multidisciplinary teams when identifying patients at risk of deteriorating and dying . It helped identify patients with multiple unmet needs who would benefit from earlier , holistic needs assessment , a review of care goals , and anticipatory care planning PURPOSE Evaluate music listening for delirium prevention among patients admitted to a Trauma Intensive Care and Trauma Orthopaedic Unit . The Roy Adaptation Model provided the theoretical framework focusing on modifying context ual stimuli . METHODS R and omised controlled trial , 40 patients aged 55 and older . INTERVENTION Participants r and omly assigned to receive music listening or usual care for 60 minutes , twice a day , over three days . Pre-recorded self-selected music using an iPod and headsets , with slow tempo , low pitch and simple repetitive rhythms to alter physiologic responses . OUTCOMES Heart rate , respiratory rate , systolic and diastolic blood pressure , confusion assessment method . RESULTS Repeated measures ANOVA , F(4 , 134 ) = 4.75 , p = .001 , suggested statistically significant differences in heart rate pre/post music listening , and F(1 , 37 ) = 10.44 , p = .003 in systolic blood pressure pre/post music listening . Post-hoc analysis reported changes at three time periods of statistical significance ; ( p = .010 ) , ( p = .005 ) and ( p = .039 ) and a change in systolic blood pressure pre/post music listening ; ( p = .001 ) of statistical significance . All participants screened negative for delirium . CONCLUSION Music addresses pathophysiologic mechanisms that contribute to delirium ; neurotransmitter imbalance , inflammation and acute physiologic stressors . Music to prevent delirium is one of few that provide support in a critical care setting Background Delirium is a serious and common postoperative complication , especially in frail elderly patients . The aim of this study was to evaluate the effect of a geriatric liaison intervention in comparison with st and ard care on the incidence of postoperative delirium in frail elderly cancer patients treated with an elective surgical procedure for a solid tumour . Methods Patients over 65 years of age who were undergoing elective surgery for a solid tumour were recruited to a multicentre , prospect i ve , r and omized , controlled trial . The patients were r and omized to st and ard treatment versus a geriatric liaison intervention . The intervention consisted of a preoperative geriatric consultation , an individual treatment plan targeted at risk factors for delirium , daily visits by a geriatric nurse during the hospital stay and advice on managing any problems encountered . The primary outcome was the incidence of postoperative delirium . The secondary outcome measures were the severity of delirium , length of hospital stay , complications , mortality , care dependency , quality of life , return to an independent preoperative living situation and additional care at home . Results In total , the data of 260 patients were analysed . Delirium occurred in 31 patients ( 11.9 % ) , and there was no significant difference between the incidence of delirium in the intervention group and the usual-care group ( 9.4 % vs. 14.3 % , OR : 0.63 , 95 % CI : 0.29–1.35 ) . Conclusions Within this study , a geriatric liaison intervention based on frailty for the prevention of postoperative delirium in frail elderly cancer patients undergoing elective surgery for a solid tumour has not proven to be effective . Trial Registration Nederl and s Trial Register Trial ID NTR The Early Warning Score ( EWS ) is a simple physiological scoring system suitable for bedside application . The ability of a modified Early Warning Score ( MEWS ) to identify medical patients at risk of catastrophic deterioration in a busy clinical area was investigated . In a prospect i ve cohort study , we applied MEWS to patients admitted to the 56-bed acute Medical Admissions Unit ( MAU ) of a District General Hospital ( DGH ) . Data on 709 medical emergency admissions were collected during March 2000 . Main outcome measures were death , intensive care unit ( ICU ) admission , high dependency unit ( HDU ) admission , cardiac arrest , survival and hospital discharge at 60 days . Scores of 5 or more were associated with increased risk of death ( OR 5.4 , 95%CI 2.8 - 10.7 ) , ICU admission ( OR 10.9 , 95%CI 2.2 - 55.6 ) and HDU admission ( OR 3.3 , 95%CI 1.2 - 9.2 ) . MEWS can be applied easily in a DGH medical admission unit , and identifies patients at risk of deterioration who require increased levels of care in the HDU or ICU . A clinical pathway could be created , using nurse practitioners and /or critical care physicians , to respond to high scores and intervene with appropriate changes in clinical management Background and aims : Delirium is a common postoperative complication in elderly patients which has a serious impact on outcome in terms of morbidity and costs . We examined whether a postoperative multi-factorial intervention program can reduce delirium and improve outcome in patients with femoral neck fractures . Methods : One hundred and ninety-nine patients , aged 70 years and over ( mean age±SD , 82±6 , 74 % women ) , were r and omly assigned to postoperative care in a specialized geriatric ward or a conventional orthopedic ward . The intervention consisted of staff education focusing on the assessment , prevention and treatment of delirium and associated complications . The staff worked as a team , applying comprehensive geriatric assessment , management and rehabilitation . Patients were assessed using the Mini Mental State Examination and the Organic Brain Syndrome Scale , and delirium was diagnosed according to DSM-IV criteria . Results : The number of days of postoperative delirium among intervention patients was fewer ( 5.0±7.1 days vs 10.2±13.3 days , p=0.009 ) compared with controls . A lower proportion of intervention patients were delirious postoperatively than controls ( 56/102 , 54.9 % vs 73/97 , 75.3 % , p=0.003 ) . Eighteen percent in the intervention ward and 52 % of controls were delirious after the seventh postoperative day ( p<0.001 ) . Intervention patients suffered from fewer complications , such as decubitus ulcers , urinary tract infections , nutritional complications , sleeping problems and falls , than controls . Total postoperative hospitalization was shorter in the intervention ward ( 28.0±17.9 days vs 38.0±40.6 days , p=0.028 ) . Conclusions : Patients with postoperative delirium can be successfully treated , result ing in fewer days of delirium , fewer other complications , and shorter length of hospitalization OBJECTIVES To investigate whether an education program and a reorganization of nursing and medical care improved the outcome for older delirious patients . DESIGN Prospect i ve intervention study . SETTING Department of General Internal Medicine , Sundsvall Hospital , Sweden . PARTICIPANTS Four hundred patients , aged 70 and older , consecutively admitted to an intervention or a control ward . INTERVENTION The intervention consisted of staff education focusing on the assessment , prevention , and treatment of delirium and on caregiver-patient interaction . Reorganization from a task-allocation care system to a patient-allocation system with individualized care . MEASUREMENTS The patients were assessed using the Organic Brain Syndrome Scale and the Mini-Mental State Examination on Days 1 , 3 , and 7 after admission . Delirium was diagnosed according to Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , criteria . RESULTS Delirium was equally common on the day of admission at the two wards , but fewer patients remained delirious on Day 7 on the intervention ward ( n=19/63 , 30.2 % vs 37/62 , 59.7 % , P=.001 ) . The mean length of hospital stay+/-st and ard deviation was significantly lower on the intervention ward then on the control ward ( 9.4+/-8.2 vs 13.4+/-12.3 days , P<.001 ) especially for the delirious patients ( 10.8+/-8.3 vs 20.5+/-17.2 days , P<.001 ) . Two delirious patients in the intervention ward and nine in the control ward died during hospitalization ( P=.03 ) . CONCLUSION This study shows that a multifactorial intervention program reduces the duration of delirium , length of hospital stay , and mortality in delirious patients CONTEXT The Palliative Care Research Cooperative Group ( PCRC ) is the first clinical trials cooperative for palliative care in the U.S. OBJECTIVES To describe barriers and strategies for recruitment during the inaugural PCRC clinical trial . METHODS The parent study was a multisite r and omized controlled trial enrolling adults with life expectancy anticipated to be one to six months , r and omized to discontinue statins ( intervention ) vs. to continue on statins ( control ) . To study recruitment best practice s , we conducted semistructured interviews with 18 site principal investigators ( PIs ) and clinical research coordinators ( CRCs ) and review ed recruitment rates . Interviews covered three topics : 1 ) successful strategies for recruitment , 2 ) barriers to recruitment , and 3 ) optimal roles of the PI and CRC . RESULTS All eligible site PIs and CRCs completed interviews and provided data on statin protocol recruitment . The parent study completed recruitment of 381 patients . Site enrollment ranged from 1 to 109 participants , with an average of 25 enrolled per site . Five major barriers included difficulty locating eligible patients , severity of illness , family and provider protectiveness , seeking patients in multiple setting s , and lack of re sources for recruitment activities . Five effective recruitment strategies included systematic screening of patient lists , thoughtful messaging to make research relevant , flexible protocol s to accommo date patients ' needs , support from clinical champions , and the additional re sources of a trials cooperative group . CONCLUSION The recruitment experience from the multisite PCRC yields new insights into methods for effective recruitment to palliative care clinical trials . These results will inform training material s for the PCRC and may assist other investigators in the field OBJECTIVES To develop and test the effect of a nurse-led interdisciplinary intervention program for delirium on the incidence and course ( severity and duration ) of delirium , cognitive functioning , functional rehabilitation , mortality , and length of stay in older hip-fracture patients . DESIGN Longitudinal prospect i ve before/after design ( sequential design ) . SETTING The emergency room and two traumatological units of an academic medical center located in an urban area in Belgium . PARTICIPANTS 60 patients in an intervention cohort ( 81.7 % females , median age = 82 , interquartile range ( IQR ) = 13 ) and another 60 patients in a usual care/nonintervention cohort ( 80 % females , median age = 80 , IQR = 12 ) . INTERVENTION ( 1 ) Education of nursing staff , ( 2 ) systematic cognitive screening , ( 3 ) consultative services by a delirium re source nurse , a geriatric nurse specialist , or a psychogeriatrician , and ( 4 ) use of a scheduled pain protocol . MEASUREMENTS All patients were monitored for signs of delirium , as measured by the Confusion Assessment Method ( CAM ) . Severity of delirium was assessed using a variant of the CAM . Cognitive and functional status were measured by the Mini-Mental State Examination ( MMSE ) ( including subscales of memory , linguistic ability , concentration , and psychomotor executive skills ) and the Katz Index of activities of daily living ( ADLs ) , respectively . RESULTS Although there was no significant effect on the incidence of delirium ( 23.3 % in the control vs 20.0 % in the intervention cohort ; P = .82 ) , duration of delirium was shorter ( P = .03 ) and severity of delirium was less ( P = .0049 ) in the intervention cohort . Further , clinical ly higher cognitive functioning was observed for the delirious patients in the intervention cohort compared with the nonintervention cohort . Additionally , a trend toward decreased length of stay postoperatively was noted for the delirious patients in the intervention cohort . Despite these positive intervention effects , no effect on ADL rehabilitation was found . Results for risk of mortality were inconclusive . CONCLUSIONS This study demonstrated the beneficial effects of an intervention program focusing on early recognition and treatment of delirium in older hip-fracture patients and confirms the reversibility of the syndrome in view of the delirium 's duration and severity Context Although delirium is common among hospitalized patients and is associated with adverse outcomes , it often goes unrecognized . A brief and simple means of applying the most widely used diagnostic tool for delirium , the Confusion Assessment Method ( CAM ) , would be helpful in fostering recognition of delirium and its evaluation and treatment . Contribution This study vali date d a 3-minute version of the CAM ( called the 3D-CAM ) as a sensitive and specific diagnostic tool in hospitalized patients , including those with and without dementia . Implication Use of the 3D-CAM should aid in the recognition of delirium in hospitalized patients . The Editors Delirium is common , leads to other adverse outcomes , and is costly in hospitalized older persons ( 13 ) . Despite increasing awareness of its importance , most delirium , particularly hypoactive delirium and delirium superimposed on dementia , still goes unrecognized ( 13 ) . Prompt recognition of delirium is the first step in appropriate management , which involves careful review for reversible contributors , prevention of complications ( including ensuring patient safety ) , and cognitive and physical rehabilitation ( 1 ) . Evidence suggests that this approach can shorten the duration of delirium and improve its associated adverse outcomes ( 1 , 3 ) . The Confusion Assessment Method ( CAM ) , developed in 1990 ( 4 ) , has been widely adopted . A recent comparison of diagnostic methods suggests that the CAM is the best-performing bedside delirium assessment tool ( 5 ) . Although the CAM is widely used in the literature to define delirium ( 6 ) , it can be challenging to operationalize in the clinical setting because it requires cognitive assessment and substantial interviewer training . Moreover , application of the CAM varies greatly , which can lead to differential performance in detecting delirium ( 5 ) . A brief , structured assessment of mental status that operationalizes the CAM algorithm would be extremely helpful to accelerate widespread ascertainment of delirium in high-risk patients ( 4 , 5 ) . Therefore , our overall goal was to develop and vali date the 3D-CAM , which is a new 3-minute diagnostic assessment for delirium using the CAM algorithm . Our aims were to create the 3D-CAM using model selection methods to finalize items , determine thresholds for the presence or absence of each of the 4 CAM diagnostic features , and prospect ively vali date the 3D-CAM by comparing it with a reference st and ard that included an extensive clinical evaluation in a new population of older general medicine patients with a high burden of baseline cognitive impairment and comorbid conditions . Methods Derivation of the 3D-CAM We started with a data set of 4598 structured delirium assessment s from a previously completed multisite trial of the delirium-abatement program conducted in 8 postacute care facilities ( 7 ) . In previously published work on 3D-CAM derivation , we mapped more than 120 items from this assessment to the 4 CAM diagnostic features ( 8) and used item response theory ( 9 ) to identify the 36 most informative items for the identification of these features ( 10 ) ( Appendix Table 1 ) . Appendix Table 1 . List of Most Informative Items for the 4 CAM Diagnostic Features We further reduced these 36 items using logistic regression and assembled the most useful subset from each of the 4 CAM diagnostic features to create the 3D-CAM . We used regression coefficients to determine the weight of each item and threshold for determining the presence or absence of each of the features : acute change or fluctuating course , inattention , disorganized thinking , and altered level of consciousness . For each feature , the best-performing approach weighted each cognitive testing item , patient symptom question , and interviewer observation equally . Moreover , each feature was rated as present if any one of the items ( cognitive test result , reported symptom , or observation item ) was rated as present . Once each feature was rated , the presence of delirium was determined by the CAM diagnostic algorithm , which required the presence of features 1 and 2 and either 3 or 4 ( Figure 1 ) . For more details , see the Supplement . Figure 1 . Overview of the 3D-CAM assessment . The CAM diagnostic algorithm is depicted , with the 3D-CAM items and scoring summarized under each CAM diagnostic feature ( 4 ) . Supplement 1 . Data Supplement Supplement 2 . Original Version ( PDF ) Once we selected the items and defined the scoring algorithm for the 3D-CAM , we made a preliminary assessment of its diagnostic accuracy . From the data set of 4598 assessment s , we used only the 3D-CAM items and the aforementioned algorithm to score the CAM algorithm . We then compared the presence or absence of delirium generated from this approach with the results of the full 160-item structured delirium assessment ( 11 ) . In this initial derivation work , the 3D-CAM achieved 92 % sensitivity ( 95 % CI , 90 % to 94 % ) and 93 % specificity ( CI , 92 % to 93 % ) relative to the full assessment , which met our goal and allowed us to proceed with the prospect i ve validation . Prospect i ve Validation Study Study Population We enrolled participants from a large urban teaching hospital in Boston , Massachusetts . Inclusion criteria were age 75 years or older , admission to general medicine or geriatric medicine services , ability to communicate effectively in English , no terminal conditions , expected hospital stay of 2 days or more , and no previous study participant . Experienced clinicians ( clinical psychologists and advanced practice nurses ) performed the screening . After approval from the attending physician was obtained , each eligible patient was approached for informed consent . If the patient was unable to provide consent , the design ated surrogate decision maker was contacted . Study protocol and informed consent procedures were approved by the institutional review board . Reference St and ard Delirium Assessment The operational reference st and ard diagnosis of delirium was based on an extensive face-to-face interview ( 45 minutes ) , medical record review , and input from the patient 's nurse and available family members . This assessment included the reason for hospital admission and hospital course ; presence of cognitive concern before and during the hospitalization ; family , social , and functional history ; Montreal Cognitive Assessment , a 30-item assessment that takes approximately 20 minutes to administer ( 12 ) ; Geriatric Depression Scale to evaluate for presence of depressive symptoms ( 13 ) ; and medical record review . This review included quantification of comorbid conditions using the Charlson index ( 14 ) , diagnosis of dementia or mild cognitive impairment ( MCI ) before hospitalization , determination of functional status using the basic and instrumental activities of daily living scales ( 15 , 16 ) , and a list of psychoactive medications administered . If the assessment indicated potential cognitive impairment ( Montreal Cognitive Assessment score 23 ) ( 12 ) , the clinical assessor conducted a proxy interview to assist with determining the patient 's baseline mental status relevant to a possible diagnosis of dementia versus a history of lifelong , developmental , cognitive limitations . The proxy interview included ascertainment of a cognitive concern before and during the hospitalization , ascertainment of whether specific cognitive deficits evident on testing existed before hospitalization , confirmation of functional status obtained from the medical record , and a proxy-based screening question naire for dementia ( the AD8 , which is a brief informant interview to detect dementia ) ( 17 ) . The final delirium diagnoses were adjudicated by a study panel , including the clinical assessor ( psychologist or advanced practice nurse ) , the principal study investigator , a geriatrician , and a board-certified neuropsychologist , using criteria from the Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition ( 18 ) . For patients not meeting delirium criteria , the panel adjudicated the presence or absence of subsyndromal delirium ( 19 ) , which was defined by the presence of acute change or fluctuating course plus inattention , disorganized thinking , or altered level of consciousness . The panel was blinded to the results of subsequent 3D-CAM testing . A geropsychiatrist subsequently readjudicated a 10 % sub sample ( 10 r and omly selected participants with delirium and 10 without ) blinded to the original results to verify the panel adjudication process . In addition to determining delirium status , the panel adjudicated the presence or absence of cognitive impairment at baseline , including dementia or MCI , using the National Institute on Aging and Alzheimer 's Association criteria ( 20 , 21 ) . ( For details of data used for adjudication of dementia and MCI , see the Supplement . ) 3D-CAM Assessment s After the reference st and ard assessment , the 3D-CAM was administered by research assistants ( RAs ) who were blinded to the results of the reference st and ard . A total of 8 RAs participated in the validation study , and each evaluated between 4 and 49 participants , based on participant and RA availability . Before the start of the study , each RA had a 1- to 2-hour training session on the use of the 3D-CAM , including practice in administering the instrument to each other and to actual patients . To assess interrater reliability , 50 % of the participants were selected to have a second 3D-CAM assessment based on a r and om-number sequence . The second 3D-CAM assessment was blinded to the reference st and ard and first 3D-CAM assessment s. All 8 RAs , representing 18 distinct pairs of raters , participated in the reliability study . Each pair evaluated between 1 to 19 participants also based on participant and RA availability . To ensure temporal proximity , all assessment s ( reference st and ard and first or second 3D-CAM assessment ) were completed within a 2-hour period between 11 a.m. and 2 p.m. ( Figure 2 ) . Figure 2 . Study flow diagram . All assessment s were completed within 2 hours of each other , and Bright light therapy is a method of maintaining or restoring the natural circadian rhythm by assisting daytime awakening using bright lights . Postoperative delirium is one of the potential complications encountered by patients receiving postoperative care in the intensive care unit ( ICU ) , but there have been no studies on the use of light for the prevention of postoperative delirium . The objective of this study was to examine whether the circadian rhythms of patients after surgery for oesophageal cancer can be adjusted and whether the postoperative delirium crisis rate can be reduced by bright light therapy . The subjects were 11 patients operated on for oesophageal cancer in Osaka University Hospital . After informed consent was obtained , they were divided into a study group and a control group by a r and om sampling method . After removal of the endotracheal tube , the study group was exposed to light . The light intensity was about 5000lx immediately before the eyes , and the distance from the light source was about 100 cm . The control group was placed in a natural lighting environment after extubation . In both groups , the rhythms of physical activities and autonomic activities were monitored after surgery , and delirium was evaluated . A significant difference was observed in the delirium score between the study group and control group on the morning of day 3 of bright light therapy by the Mann-Whitney U-test ( P=0.014 ) . The study group could begin ambulation about 2 days earlier than the control group . Bright light therapy may reduce the rate of postoperative delirium and make early ambulation possible . However , our study involved a very small sample size . We want to increase the sample in the future after having review ed clinical application methods STUDY OBJECTIVE Delirium is a common form of acute brain dysfunction with prognostic significance . Health care professionals caring for older emergency department ( ED ) patients miss delirium in approximately 75 % of cases . This error results from a lack of available measures that can be performed rapidly enough to be incorporated into clinical practice . Therefore , we developed and evaluated a novel 2-step approach to delirium surveillance for the ED . METHODS This prospect i ve observational study was conducted at an academic ED in patients aged 65 years or older . A research assistant and physician performed the Delirium Triage Screen ( DTS ) , design ed to be a highly sensitive rule-out test , and the Brief Confusion Assessment Method ( bCAM ) , design ed to be a highly specific rule-in test for delirium . The reference st and ard for delirium was a comprehensive psychiatrist assessment using Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , Text Revision criteria . All assessment s were independently conducted within 3 hours of one another . Sensitivities , specificities , and likelihood ratios with their 95 % confidence intervals ( 95 % CIs ) were calculated . RESULTS Of 406 enrolled patients , 50 ( 12.3 % ) had delirium diagnosed by the psychiatrist reference st and ard . The DTS was 98.0 % sensitive ( 95 % CI 89.5 % to 99.5 % ) , with an expected specificity of approximately 55 % for both raters . The DTS 's negative likelihood ratio was 0.04 ( 95 % CI 0.01 to 0.25 ) for both raters . As the complement , the bCAM had a specificity of 95.8 % ( 95 % CI 93.2 % to 97.4 % ) and 96.9 % ( 95 % CI 94.6 % to 98.3 % ) and a sensitivity of 84.0 % ( 95 % CI 71.5 % to 91.7 % ) and 78.0 % ( 95 % CI 64.8 % to 87.2 % ) when performed by the physician and research assistant , respectively . The positive likelihood ratios for the bCAM were 19.9 ( 95 % CI 12.0 to 33.2 ) and 25.2 ( 95 % CI 13.9 to 46.0 ) , respectively . If the research assistant DTS was followed by the physician bCAM , the sensitivity of this combination was 84.0 % ( 95 % CI 71.5 % to 91.7 % ) and specificity was 95.8 % ( 95 % CI 93.2 % to 97.4 % ) . If the research assistant performed both the DTS and bCAM , this combination was 78.0 % sensitive ( 95 % CI 64.8 % to 87.2 % ) and 97.2 % specific ( 95 % CI 94.9 % to 98.5 % ) . If the physician performed both the DTS and bCAM , this combination was 82.0 % sensitive ( 95 % CI 69.2 % to 90.2 % ) and 95.8 % specific ( 95 % CI 93.2 % to 97.4 % ) . CONCLUSION In older ED patients , this 2-step approach ( highly sensitive DTS followed by highly specific bCAM ) may enable health care professionals , regardless of clinical background , to efficiently screen for delirium . Larger , multicenter trials are needed to confirm these findings and to determine the effect of these assessment s on delirium recognition in the ED OBJECTIVES To analyze the effectiveness of a multicomponent intervention integrated into daily practice for the prevention of in-hospital delirium in elderly patients . DESIGN Controlled study comparing an intervention in a geriatric unit ( GI ) with usual care in two internal medicine services ( UC ) . SETTING University hospital in Madrid , Spain . PARTICIPANTS Five hundred forty-two consecutive patients ( 170 GI , 372 UC ) , aged 70 and older , with any of the risk criteria for delirium ( cognitive impairment , visual impairment , acute disease severity , dehydration ) . INTERVENTION Educational measures and specific actions in seven risk areas ( orientation , sensory impairment , sleep , mobilization , hydration , nutrition , drug use ) . Daily monitoring of adherence . MEASUREMENTS Baseline characteristics , risk factors for delirium , and quality care indicators were analyzed . The primary endpoint was incidence of delirium assessed daily . The secondary endpoint was functional decline , defined as loss of independence in any of the activities of daily living . The intervention effect was evaluated using logistic regression analysis . RESULTS Delirium affected 11.7 % of the GI group and 18.5 % of the UC group ( P=.04 ) . After adjustment for confounders , the intervention was associated with lower incidence of delirium ( odds ratio=0.4 , 95 % confidence interval=0.24 - 0.77 ; P=.005 ) . In the patients who experienced delirium , severity , length , and recurrence of episodes were similar in both groups . Adherence to the intervention protocol s was 75.7 % . The intervention reduced the rate of functional decline ( 45.5 % in GI vs 56.3 % in UC , P=.03 ) and improved other quality indicators ( e.g. , mobilization and physical restraints reduction ) . CONCLUSION A multicomponent , nonpharmacological intervention integrated into routine practice reduces delirium during hospitalization in older patients , improves quality of care , and can be implemented without additional re sources in a public healthcare system Objective To develop and vali date an instrument for use in the intensive care unit to accurately diagnose delirium in critically ill patients who are often nonverbal because of mechanical ventilation . Design Prospect i ve cohort study . Setting The adult medical and coronary intensive care units of a tertiary care , university-based medical center . Patients Thirty-eight patients admitted to the intensive care units . Measurements and Main Results We design ed and tested a modified version of the Confusion Assessment Method for use in intensive care unit patients and called it the CAM-ICU . Daily ratings from intensive care unit admission to hospital discharge by two study nurses and an intensivist who used the CAM-ICU were compared against the reference st and ard , a delirium expert who used delirium criteria from the Diagnostic and Statistical Manual of Mental Disorders ( fourth edition ) . A total of 293 daily , paired evaluations were completed , with reference st and ard diagnoses of delirium in 42 % and coma in 27 % of all observations . To include only interactive patient evaluations and avoid repeat-observer bias for patients studied on multiple days , we used only the first-alert or lethargic comparison evaluation in each patient . Thirty-three of 38 patients ( 87 % ) developed delirium during their intensive care unit stay , mean duration of 4.2 ± 1.7 days . Excluding evaluations of comatose patients because of lack of characteristic delirium features , the two critical care study nurses and intensivist demonstrated high interrater reliability for their CAM-ICU ratings with kappa statistics of 0.84 , 0.79 , and 0.95 , respectively ( p < .001 ) . The two nurses ’ and intensivist ’s sensitivities when using the CAM-ICU compared with the reference st and ard were 95 % , 96 % , and 100 % , respectively , whereas their specificities were 93 % , 93 % , and 89 % , respectively . Conclusions The CAM-ICU demonstrated excellent reliability and validity when used by nurses and physicians to identify delirium in intensive care unit patients . The CAM-ICU may be a useful instrument for both clinical and research purpose s to monitor delirium in this challenging patient population OBJECTIVE To assess a systematic intervention in cases of delirium in elderly in patients . DESIGN R and omized , controlled trial . SETTING University-affiliated , primary acute care hospital . PATIENTS Patients aged 75 years or over admitted to the medical department . They were screened within 24 hours after admission , and 88 patients with delirium ( according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders , third revised edition ) were detected and enrolled in the trial . The patients were r and omly allocated to the treatment group ( 42 ) or the control group ( 46 ) ; all were followed up until the end of the study . INTERVENTION Patients were assessed on enrolment and 1 , 2 , 4 and 8 weeks later . Those in the treatment group received a consultation by a geriatric internist or psychiatrist and follow-up by a liaison nurse . Those in the control group received regular medical care . OUTCOME MEASURES Short Portable Mental Status Question naire ( SPMSQ ) , Crichton Geriatric Behavioural Rating Scale ( CGBRS ) , use of restraints , length of hospital stay , discharge to a setting providing more care than was needed before admission and mortality rate . RESULTS Two weeks after admission , patients in the treatment group showed an improvement in their mean SPMSQ scores , from 8.2 ( st and ard deviation [ SD ] 1.9 ) to 7.9 ( SD 2.5 ) , whereas the control group showed a deterioration , from 8.4 ( SD 1.7 ) to 9.1 ( SD 1.1 ) ; this difference had disappeared by the end of the 8-week period ( p < 0.05 ) . Mean CGBRS scores were higher in the treatment group ( 32.0 [ SD 8.6 ] ) than the control group ( 28.5 [ SD 9.4 ] ) on enrolment and had improved more markedly by the end of the 8-week period ( to 23.9 [ SD 7.8 ] v. 25.0 [ SD 7.0 ] , p = 0.06 ) . There was no statistically significant difference between the groups in use of restraints , length of hospital stay , discharge to a setting providing more care than was needed before admission or mortality rate . CONCLUSION The beneficial effects of systematic detection and intervention in cases of delirium in elderly in patients were small BACKGROUND A decreased incidence of delirium following the application of non-pharmacologic intervention protocol s to several patient population s has been previously reported . However , few studies have been conducted to examine the effects of their application to intensive care unit ( ICU ) patients . OBJECTIVES To examine the effects of applying a tailored delirium preventive protocol , developed by the authors , to ICU patients by analyzing its effects on delirium incidence , in-hospital mortality , ICU readmission , and length of ICU stay in a Korean hospital . DESIGN A single-blind r and omized controlled trial . SETTING S A 1049-bed general hospital with a 105-bed ICU . PARTICIPANTS Sixty and 63 ICU patients were r and omly assigned to the intervention and control groups , respectively . METHODS The research ers applied the delirium prevention protocol to the intervention group every day for the first 7 days of ICU hospitalization . Delirium incidence , mortality , and re-admission to the ICU during the same hospitalization period were analyzed by logistic regression analysis ; the 7- and 30-day in-hospital mortality by Kaplan-Meier survival and Cox proportional hazard regression analysis ; and length of ICU stay was assessed by linear regression analysis . RESULTS Application of the protocol had no significant effect on delirium incidence , in-hospital mortality , re-admission to the ICU , or length of ICU stay . Whereas the risk of 30-day in-hospital mortality was not significantly lower in the intervention than in the control group ( OR : 0.33 ; 95 % CI : 0.10 - 1.09 ) , we found a significantly decreased 7-day in-hospital mortality in the intervention group after protocol application ( HR : 0.09 ; 95 % CI : 0.01 - 0.72 ) . CONCLUSIONS Application of a tailored delirium prevention protocol to acute stage patients during the first 7 days of ICU hospitalization appeared to reduce the 7-day in-hospital risk of mortality only for this patient population OBJECTIVES Most strategies for delirium prevention in older hospitalized patients are common good clinical geriatric care . We investigated whether acute geriatric ward ( AGW ) hospitalization , compared with acute general medical ward ( AGMW ) hospitalization , is associated with reduced incident delirium in older medical in patients . DESIGN prospect i ve observational study . SETTING a tertiary care , university hospital in Torino . PARTICIPANTS consecutive medical patients 70 years or older admitted from the emergency department to an AGW and to an AGMW were included . MEASUREMENTS Baseline measures included demography , functional and psychocognitive status , comorbidity , physiological and clinical severity of acute illness . Incident delirium was evaluated by qualified psychiatrists according to the Confusion Assessment Method and the Delirium Rating Scale . RESULTS Delirium occurred in 8 of 121 patients admitted to AGW ( 6.6 % ) and in 20 of 131 patients admitted to AGMW ( 15.2 % ) . After adjustment for significant differences in baseline covariates between groups , AGW hospitalization remained independently associated with less incident delirium ( relative risk 0.90 , 95 % confidence interval : 0.024 - 0.331 , p < 0.001 ) . In a multivariable logistic model with delirium incidence as independent variable , AGW hospitalization was independently associated with lower delirium incidence ( relative risk 0.039 , 95 % confidence interval : 0.007 - 0.214 , p < 0.001 ) , whereas greater cognitive impairment ( p < 0.001 ) , higher Acute Physiology and Chronic Health Evaluation II score ( p 0.001 ) and recent stressful events ( p < 0.001 ) were associated with increased delirium incidence . CONCLUSION AGW hospitalization is associated with less incident delirium among older medical in patients . Despite inherent limitations of observational studies , these hypothesis-generating findings add to previous evidence of potential benefit in delirium prevention from geriatric consultation in several hospital setting BACKGROUND Delirium is a common problem for frail , older patients in hospital and a marker of poor outcome and mortality . The aim of this study was to test a volunteer-mediated delirium prevention programme for efficacy , cost-effectiveness and sustainability on an Australian geriatric ward . METHODS Two controlled before- and -after studies were conducted . In study 1 , 37 patients ( > 70 years , admitted to the geriatric wards ) were enrolled during 5 months in 2003 for intensive individual study . Twenty-one patients received usual care and 16 patients received the volunteer-mediated intervention of daily orientation , therapeutic activities , feeding and hydration assistance , vision and hearing protocol s. In study 2 , we examined the effects of a general implementation for the whole department by measuring use of assistants in nursing , who were employed for individual nursing of delirious patients . RESULTS In study 1 , we found a lower incidence ( intervention vs control , 6.3 % vs 38 % ; P = 0.032 ) and lower severity of delirium ( 1.2 vs 5.1 ; P = 0.045 ) . There was a trend towards decreased duration of delirium ( 5.0 vs 12.5 ; P = 0.64 ) . In study 2 , use of assistants in nursing was reduced by 314 h per month suggesting a total annual saving of 129,186 Australian dollars for the hospital . CONCLUSION The programme prevents delirium and improves outcomes for elderly in patients . Cost-effectiveness supports the continuation of the programme and extension to other geriatric units CONTEXT Based on the clinical care pathway of delirium in palliative care ( PC ) , a published analytic framework ( AF ) formulated research questions in key domains and recommended a scoping review to identify evidence gaps . OBJECTIVES To produce a literature map for key domains of the published AF : screening , prognosis and diagnosis , management , and the health-related outcomes . METHODS A st and ard scoping review framework was used by an interdisciplinary study team of nurse- and physician-delirium research ers , an information specialist , and review method ologists to conduct the review . Knowledge user engagement provided context in refining 19 AF questions . A peer- review ed search strategy identified citations in Medline , PsycINFO , Embase , and CINAHL data bases between 1980 and 2018 . Two review ers independently screened records for inclusion using explicit study eligibility criteria for the population , design , delirium diagnosis , and investigational intent . RESULTS Of 104 studies reporting empirical data and meeting eligibility criteria , most were conducted in patients with cancer ( 73.1 % ) and in inpatient PC units ( 52 % ) . The most frequent study design was a one or more group , nonr and omized trial or cohort ( 67.3 % ) . Evidence gaps were identified : delirium risk prediction ; comparative effectiveness and harms of prevention , variability in delirium management across PC setting s , advanced directive and substitute decision-maker input , and transition of care location ; and estimating delirium reversibility . Future rigorous primary studies are required to address these gaps and preliminary concerns regarding the quality of extant literature . CONCLUSION Substantial evidence gaps exist , providing opportunities for future research regarding the assessment , prognosis , and management of delirium in PC setting Importance Antipsychotics are widely used for distressing symptoms of delirium , but efficacy has not been established in placebo-controlled trials in palliative care . Objective To determine efficacy of risperidone or haloperidol relative to placebo in relieving target symptoms of delirium associated with distress among patients receiving palliative care . Design , Setting , and Participants A double-blind , parallel-arm , dose-titrated r and omized clinical trial was conducted at 11 Australian inpatient hospice or hospital palliative care services between August 13 , 2008 , and April 2 , 2014 , among participants with life-limiting illness , delirium , and a delirium symptoms score ( sum of Nursing Delirium Screening Scale behavioral , communication , and perceptual items ) of 1 or more . Interventions Age-adjusted titrated doses of oral risperidone , haloperidol , or placebo solution were administered every 12 hours for 72 hours , based on symptoms of delirium . Patients also received supportive care , individualized treatment of delirium precipitants , and subcutaneous midazolam hydrochloride as required for severe distress or safety . Main Outcome and Measures Improvement in mean group difference of delirium symptom score ( severity range , 0 - 6 ) between baseline and day 3 . Five a priori secondary outcomes : delirium severity , midazolam use , extrapyramidal effects , sedation , and survival . Results Two hundred forty-seven participants ( mean [ SD ] age , 74.9 [ 9.8 ] years ; 85 women [ 34.4 % ] ; 218 with cancer [ 88.3 % ] ) were included in intention-to-treat analysis ( 82 receiving risperidone , 81 receiving haloperidol , and 84 receiving placebo ) . In the primary intention-to-treat analysis , participants in the risperidone arm had delirium symptom scores that were significantly higher than those among participants in the placebo arm ( on average 0.48 Units higher ; 95 % CI , 0.09 - 0.86 ; P = .02 ) at study end . Similarly , for those in the haloperidol arm , delirium symptom scores were on average 0.24 Units higher ( 95 % CI , 0.06 - 0.42 ; P = .009 ) than in the placebo arm . Compared with placebo , patients in both active arms had more extrapyramidal effects ( risperidone , 0.73 ; 95 % CI , 0.09 - 1.37 ; P = .03 ; and haloperidol , 0.79 ; 95 % CI , 0.17 - 1.41 ; P = .01 ) . Participants in the placebo group had better overall survival than those receiving haloperidol ( hazard ratio , 1.73 ; 95 % CI , 1.20 - 2.50 ; P = .003 ) , but this was not significant for placebo vs risperidone ( hazard ratio , 1.29 ; 95 % CI , 0.91 - 1.84 ; P = .14 ) . Conclusions and Relevance In patients receiving palliative care , individualized management of delirium precipitants and supportive strategies result in lower scores and shorter duration of target distressing delirium symptoms than when risperidone or haloperidol are added . Trial Registration anzctr.org.au Identifier : ACTRN12607000562471 |
1,293 | 22,592,710 | AUTHORS ' CONCLUSIONS There is only limited evidence to support the effectiveness of local cooling treatments ( ice packs , cold gel pads , cold/iced baths ) applied to the perineum following childbirth to relieve pain | BACKGROUND Perineal trauma is common during childbirth and may be painful .
Contemporary maternity practice includes offering women numerous forms of pain relief , including the local application of cooling treatments .
OBJECTIVES To evaluate the effectiveness and side effects of localised cooling treatments compared with no treatment , other forms of cooling treatments and non-cooling treatments . | The objective of the present study was to compare three methods of cryotherapy in healthy non-pregnant women . This is a r and omized controlled clinical trial that was conducted by 32 undergraduates of a private nursing college in the city of Sao Paulo , divided into three groups ( iced water , soft ice , ice gel ) . The temperatures were verified ( axillary , thigh , of the three ice packs ) between zero and twenty minutes . The temperatures of the packs were the following : soft ice , from negative 9 degrees C to 2 degrees C ; iced water , from 0 degrees C to 8 degrees C ; and ice gel from negative 11 degrees C to 2 degrees C. There was a significant difference between the average thigh temperature values at 10 minutes ( p = 0.007 ) , 15 minutes ( p = 0.003 ) and 20 minutes ( p = 0.005 ) . The gel was the most efficient cooling method . The three cryotherapy methods achieved the recommended temperature for analgesia and may be tested in women with perineal pain after childbirth Systematic review s of r and omized controlled trials have demonstrated that episiotomies should not be performed routinely and that performing episiotomies in no more than 10 % of nulliparas being delivered vaginally would be safe . Episiotomy rates are reported for nulliparous and multiparous women in hospitals in Argentina Brazil Bolivia Chile the Democratic Republic of Congo Ecuador India Tibet Uruguay Venezuela and Zambia . These hospitals are part of the National Institute of Child Health and Human Development ’s Global Network for Women ’s and Children ’s Health Research . Data were collected using a survey form completed by investigators at 7 sites between April and December 2003 . All sites collected hospital-based data extracted from routine labor and delivery logbooks or from labor and delivery records . A site refers to an investigative team reporting data from 1 or more countries participating in the Global Network . Episiotomy rates are reported both by site and by mean rates and ranges across sites . ( excerpt The effect of cold sitz baths for relieving perineal pain in the postpartum period after an episiotomy was evaluated . Forty patients took both cold and warm sitz baths with r and om assignment of the initial bath . Patients rated the degree of perineal pain before and after each sitz bath and at half-hour and one-hour intervals after each bath . A pain scale using 0 - 5 , 0 representing no pain and 5 representing extreme pain , was used . Analysis of pain scale scores using a two-way analysis of variance with replications showed that cold sitz baths were significantly more effective in relieving perineal pain . The greatest amount of pain relief was experienced immediately after the cold sitz baths BACKGROUND The full extent of genital tract trauma in spontaneous births is not well documented . The purpose of this study was to describe the range and extent of childbirth trauma and related postnatal pain using data from a large r and omized clinical trial of perineal management techniques ( n = 5471 ) . METHODS Descriptive analysis was conducted on trial participants who delivered spontaneously at term and were examined by their midwife after birth ( n = 5404 ) . Data are reported for sites of trauma , and the relation to episiotomy , suturing , and maternal reports of pain at 2 days , 10 days , and 3 months after birth . RESULTS Eighty-five percent of all women experienced some form of trauma , with first- or second-degree perineal lacerations occurring in two-thirds of women and outer vaginal tears occurring in one-half . Tears to the rectum and vaginal vault were more common with episiotomy . Nearly all unsutured trauma was restricted to perineal first- or second-degree , outer vaginal , and labial sites . Pain declined over time , and a gradient in pain was observed according to the site and complexity of trauma . CONCLUSIONS Genital tract trauma is extremely common with spontaneous vaginal birth . Effective measures to prevent or reduce its occurrence would benefit many new mothers OBJECTIVE To evaluate the effectiveness of st and ard regimes ( ice packs and Epifoam ) at relieving perineal trauma and compare these with a new cooling device ( maternity gel pad ) . DESIGN A r and omised controlled trial involving three treatment groups . The women were free to choose the time of initial application ( within four hours after delivery ) in all treatment groups and the number of subsequent treatments up to 48 hours after suturing . SETTING A midwifery unit in the north of Engl and and then continued in the women 's own homes . PARTICIPANTS 120 women who had undergone an instrumental delivery and had a 48 hours post-delivery stay in a postnatal ward . MEASUREMENTS AND FINDINGS The ordinal scale of none , mild , moderate and severe was used to determine the levels of perineal oedema and bruising at initial assessment ( less than 4 hours ) , 24 hours and at 48 hours , by use of a newly developed visual evaluating tool . Self-assessed pain was recorded using a 10-point visual analogue scale within four hours , at 24 hours , 48 hours , and finally at five days after suturing . Women 's opinions as to the effectiveness of their treatment was rated by use of a 5-point scale describing the categories ; poor , fair , good , very good and excellent . A high proportion of women had some perineal oedema at initial assessment . A statistically significant difference in the proportion of women with oedema was found between treatment groups at 48 hours ( p = 0.01 ) , which was in favour of the maternity gel pad group . This was particularly noticeable for women with initial levels of mild oedema ( p = 0.017 ) . Localised treatment with the gel pad caused a significant decrease in reported pain at 48 hours in women who initially demonstrated moderate or severe pain ( p = 0.048 ) . A significant increase in the proportion of women with some bruising was seen across all treatment groups from initial assessment , through 24 hours to 48 hours ( p < 0.0005 ) . The bruising was significantly less in the gel-pad group in women who initially had no bruising ( p = 0.021 ) . There was no statistically significant effect of treatment at other initial levels of severity for oedema , bruising or pain at 24 hours , 48 hours and five days ( for pain ) . Women in the gel-pad group rated the effectiveness of their localised treatment to be significantly higher than women in the other two treatment groups ( p < 0.0005 ) . KEY CONCLUSIONS This trial demonstrated that a high proportion of women experience perineal oedema , bruising and pain following an instrumental delivery , which continues for at least five days for perineal pain , despite oral analgesia . Maternity gel pads , which were specially design ed to cool the perineal region , were more effective in alleviating perineal trauma when compared with hospital st and ard regimens and were more highly rated by women The association between episiotomy and severe ( third- and fourth-degree ) perineal lacerations was studied in 24,114 women . The overall rates of severe lacerations were 8.3 and 1.5 % for primiparous and multiparous women , respectively . Women who had midline episiotomies were nearly 50 times more likely and women who had mediolateral episiotomies were over eight times more likely to suffer a severe laceration than were women who did not undergo an episiotomy . Severe lacerations were also more common after use of forceps , in occiput transverse and posterior presentations , among women with smaller pelvic outlet measurements or lower prepregnant weight , and with larger fetuses . The same factors that caused a woman to have an increased risk of laceration also made performance of an episiotomy more likely . After statistical adjustment for these risk factors , mediolateral episiotomy was associated with a 2.5-fold reduction in the risk of severe lacerations among primiparous women , and a statistically nonsignificant 2.4-fold increase among multiparous women , compared with no episiotomy . Midline episiotomy was associated with statistically significant 4.2- and 12.8-fold increases in the risk of lacerations among primiparous and multiparous women , respectively . We conclude that the risks and benefits of midline episiotomy should be evaluated in a r and omized clinical trial that compares policies of “ usual ” versus conservative use of episiotomy Ultrasound and pulsed electromagnetic energy therapies arc increasingly used for perineal trauma sustained during childbirth . The study included 414 women with moderate or severe perineal trauma r and omly allocated to receive active ultrasound , or active pulsed electromagnetic energy , or corresponding placebo therapies ; the allocation was double‐blind for each machine . Overall , more than 90 % thought that treatment made their problem better . There were no clear differences between the groups in outcome either immediately after treatment , or 10 days or 3 months postpartum , other than more pain associated with pulsed electromagnetic energy treatment at 10 days . Bruising looked more extensive after ultrasound therapy but then seemed to resolve more quickly . Neither therapy had an effect on perineal oedema or haemorrhoids . The place of these new therapies in postnatal care should be clarified by further controlled trials before they become part of routine care Perineal discomfort from episiotomy continues to be a problem for many postpartum women . The purpose s of this study were to compare the effect of ice bag and heat lamp for the relief of perineal discomfort and to identify the sustaining time of each effect . Forty women took ice bag and heat lamp with r and om assignment of initial therapy . Women rated the degree of perineal discomfort before and after each therapy and at half-hour , tow-hour and four-hour intervals after each therapy . A discomfort scale , 18 cm graphic rating scale , was used . The results of the study were as follows : 1 . The ice bag group showed significantly lower discomfort score than the heat lamp group at the half-hour and two-hour intervals after therapy . 2 . The ice bag group showed significantly lower discomfort score for 4hrs after than before therapy , but the heat lamp group did not show significantly lower discomfort score . 3 . Neither the type of episiotomy nor the previous experience of heat therapy influenced on the effect of ice bag relieving the perineal discomfort . Therefore ice bag was significantly more effective in relieving perineal discomfort than heat lamp . Subjective responses of patients who took both therapy were very favorable toward ice bag . I suggested that nurses should provide women with adequate information about the use of ice bag and encourage to apply ice bag instead of heat lamp after episiotomy in order to promote the relief of perineal discomfort and the healing of perineal wound Objective To compare the effect of two methods of perineal management used during spontaneous vaginal delivery on the prevalence of perineal pain reported at 10 days after birth BACKGROUND Perineal pain is one of the most common causes of maternal morbidity in the early puerperium . Several r and omized trials have shown that topical application of local anesthetics is effective in reducing postepisiotomy pain , but no r and omized study has assessed the efficacy of local anesthetics for other perineal trauma . This study investigated if topically applied 2 percent lignocaine gel was an effective treatment for this group of women . METHODS A double-blind placebo controlled trial was conducted in a regional teaching hospital in the northwest of Engl and . One hundred and forty-nine women who had sustained a first- or second-degree tear were allocated by sealed envelopes to the lignocaine gel or placebo group . The primary outcome was self-reported pain at 24 hours postdelivery as measured on a numerical rating scale ( pain score ) . Secondary outcomes included pain scores at 48 hours , the need for oral analgesia , and maternal satisfaction . Based on a pilot study , we calculated that 128 women were required to detect a 25 percent difference in pain scores between the two groups with 80 percent power ( alpha = 0.05 ) . The pain scores of women in each trial arm were compared using the unpaired t test and 95 percent confidence intervals . RESULTS Women using lignocaine gel had lower average pain scores , although this only reached statistical significance at 48 hours after delivery ( p = 0.023 ) . In general , women liked using the study gel . No difference was found in consumption of oral analgesia . CONCLUSIONS This study suggested that lignocaine gel may be effective on the second postnatal day . Further research is required to assess the optimum timing of this intervention and the population that would most benefit from its use Abstract Midwives ' management of postpartum perineal pain was surveyed in 50 r and omly selected English maternity units . First line management was usually oral analgesia ( 78 % ) although some units first offered local ice , hydrocortisone and pramoxine foam ( Epifoam ) , or witch hazel . Paracetamol was the oral analgesic of choice for mild perineal pain but there was wide variation in the choice of oral analgesia for more severe pain ; the most common practice was to use paracetamol in combination with a stronger analgesic . Ice was the most popular local treatment ( 84 % of units ) but hydrocortisone/pramoxine foam ( Epifoam ) and therapeutic ultrasound were also popular . Many of the therapies mentioned in the survey remain poorly evaluated . Further controlled trials are needed to clarify their place in postnatal care Thirty healthy patients undergoing lumbar spine surgery were r and omly assigned to one of two groups for postoperative pain relief . Group 1 received morphine via patient controlled analgesia and local cooling of the wound by an externally applied cooling pad while group 2 received patient controlled analgesia alone . There was a significant reduction in morphine consumption when local cooling was applied ( 18.6 mg versus 30.2 mg at 12h , 29.0 mg versus 49.6 mg at 24 h , p < 0.05 ) . Patients were also significantly more satisfied with their overall postoperative pain management when cooling therapy was used INTRODUCTION This study evaluated the effectiveness of an ice pack applied for 20 minutes to alleviate perineal pain after spontaneous vaginal birth . METHODS We conducted a r and omized controlled trial at the Amparo Maternal Birth Center in São Paulo , Brazil . Study participants included 114 nulliparous women divided into 3 groups ( n = 38 per group ) : experimental ( ice packs on the perineum ) , placebo ( water packs at set temperature ) , and control ( no treatment ) . RESULTS A numerical scale ( 0 to 10 ) was used for pain assessment . A comparison of the average pain at the beginning and after 20 minutes showed a significant reduction of pain ( P < .001 ) in the 3 groups , and the experimental group had a lower average score for pain compared with the control group ( 1.6 versus 3.3 , P = .032 ) . DISCUSSION The use of ice packs for 20 minutes was effective for perineal pain relief after vaginal birth One thous and women were allocated at r and om to one of two perineal management policies , both intended to minimise trauma during spontaneous vaginal delivery . In one the aim was to restrict episiotomy to fetal indications ; in the other the operation was to be used more liberally to prevent perineal tears . The result ant episiotomy rates were 10 % and 51 % respectively . An intact perineum was more common among those allocated to the restrictive policy . This group experienced more perineal and labial tears , however , and included four of the five cases of severe trauma . There were no significant differences between the two groups either in neonatal state or in maternal pain and urinary symptoms 10 days and three months post partum . Women allocated to the restrictive policy were more likely to have resumed sexual intercourse within a month after delivery . These findings provide little support either for liberal use of episiotomy or for cl aims that reduced use of the operation decreases postpartum morbidity The Redness Edema Ecchymosis Discharge Approximation ( REEDA ) tool , devised to evaluate postpartum healing of the perineum following an episiotomy/laceration , was used to evaluate the effects of heat and cold on the perineum during the first 24 hours after delivery . Ninety patients were r and omly assigned to one of three treatment groups . Treatment consisted of 30 subjects applying a warm perineal pack , 30 applying a cold perineal pack , and 30 taking a warm sitz bath . Analysis of variance indicated no difference in the REEDA score before or two hours after treatment . A Pearson r correlation indicated the REEDA score was associated with a laceration and not with infant weight . Although these findings do not support assumptions from the literature , this study provides baseline data and trends for future study The efficacy of a cold compressive dressing after total knee arthroplasty ( TKA ) was prospect ively studied in 105 knees in 76 patients . All components were cemented . All patients were placed in continuous passive motion machines after operation . A cold compressive Cryocuff dressing was applied to 50 knees after operation . An ACE wrap and ice pack were applied to the knees of 55 control patients after operation . Postoperative range of motion was recorded as maximum active flexion at two to four days ( interval one ) , at seven to 14 days ( interval two ) , and four to six weeks ( interval three ) . Swelling was measured at the same time intervals by circumference at the midpatella and circumference at the distal thigh one inch proximal to the superior pole of the patella . Use of postoperative narcotics was calculated for postoperative days zero to three and for postoperative days four to seven . Wound drainage was recorded for all knees . The use of a cold compressive dressing after TKA was not associated with an increase in range of motion at any point after the operation . The Cryocuff dressing did not appreciably reduce swelling around the knee after TKA . No significant difference was found in the amount of postoperative wound drainage between the two groups of patients . In patients undergoing unilateral TKA , no significant difference existed between the narcotic requirements of control patients and patients wearing the cold compressive dressing OBJECTIVE to determine risk factors for the occurrence of severe perineal trauma ( third and fourth degree tears ) during childbirth . DESIGN a prospect i ve cohort study was conducted using the hospital 's computerised obstetric information system . Additional data were gathered on women who sustained severe perineal trauma . Descriptive statistics and logistic regression were used to assess risk factors for severe perineal trauma . Midwives were asked to comment on possible reasons for severe perineal trauma . Written responses made by midwives were analysed using content analysis . Discussion groups with midwives were held to further explore their experiences . SETTING Royal Prince Alfred Hospital , Sydney , Australia . PARTICIPANTS all women having vaginal births ( n=6595 ) in a 2-year period between 1 April 1998 and 31 March 2000 , in both the birth centre and the labour ward . MEASUREMENTS AND FINDINGS 2 % of women ( n=134 ) experienced severe perineal trauma . One hundred and twenty-two women had third-degree tears and 12 had fourth-degree tears . Primiparity , instrumental delivery , Asian ethnicity and heavier babies were associated with an elevated risk of severe perineal trauma . Midwives identified several factors they believed contributed to severe perineal trauma . These were lack of effective communication with the woman during the birth , different birth positions , delivery technique , ethnicity and obstetric influences . KEY CONCLUSIONS findings support current knowledge that primiparity , instrumental birth , heavier babies and being of Asian ethnicity are associated with increased rates of severe trauma . Specific attention needs to be paid to the strong association found between being of Asian ethnicity and experiencing severe perineal trauma . IMPLICATION S FOR PRACTICE further identification and validation of the concerns expressed by midwives to reduce severe perineal trauma is warranted so that preventative strategies can be used and research ed A prospect i ve r and omized study was performed to evaluate the role of cold compressive dressings in the postoperative treatment of total knee arthroplasty ( TKA ) . Eighty consecutive unilateral and ten bilateral primary total knee replacements were evaluated in terms of blood loss , pain relief , and range of motion . Patients in the cold compression group demonstrated an average of 548 ml in suction drainage , whereas those in the control group averaged 807 ml . This result ed in an average 3.1 mg hemoglobin drop in the cold compression group and 4.7 mg in the control group . When body habitus and weight were taken into account in the cold compression group , an average total blood loss of 1298 cc was calculated , with 744 ml arising from soft tissue extravasation . The corresponding total blood loss calculated average was 1908 ml in the control group , with 1101 ml attributed to soft tissue extravasation . Total injectable morphine per kilogram per initial 48 hours averaged 0.53 mg in the cold compression patients and 0.69 mg in the control patients . In the cold compression knees , range of motion averaged 86 degrees before operation , 53 degrees on postoperative day ( POD ) 7 , and 77 degrees on POD 14 . In the control knees , range of motion averaged 88 degrees before operation , 44 degrees on POD 7 , and 65 degrees on POD 14 . The use of cold compression in the postoperative period of TKA results in a dramatic decrease in blood loss . In addition , mild improvements are seen in early return of motion and injectable narcotic pain needs in the postoperative period |
1,294 | 31,823,103 | Some studies showed that the Mediterranean diet ( MedDiet ) had a beneficial effect on cardiac function , while others did not find any positive impact .
Nutritional supplements and hypercaloric intake had positive effects on underweight HF patients , while hypocaloric diet was beneficial in obese HF patients improving glucose control and cardiac function .
The effect of MedDiet in HF patients showed conflicting results .
Changes in the dietary pattern can reduce the evolution of HF , considering not only the quality of food but also the caloric intake .
The discriminant factor to prescribe a diet regime in HF patients is represented by body mass index ( BMI ) .
A well-balanced caloric diet represents an effective therapy in overweight HF patients to reduce the mortality rate . | Nutrition is the primary source of energy production for myocardial contractility and to maintaining cardiac efficiency .
Although many studies provided evidence of the benefits of nutritional intervention in chronic heart failure patients ( CHF ) , these effects are not still completely understood . | Background / Objectives : Growing evidence emerged about the role of diet in heart failure ( HF ) development , but data are sparse and inconclusive . We examined the association between a Mediterranean-style diet , its components and HF risk . Subjects/ Methods : Analyses were carried out in 24 008 middle-aged participants of the European Prospect i ve Investigation into Cancer and Nutrition (EPIC)-Potsdam ( Germany ) , including 209 incident HF cases within 8.2 years . The traditional Greek Mediterranean diet score ( tMED ) was used to assess dietary adherence . Cox ’s proportional hazards regression was applied to estimate the relationship between the adherence to the Mediterranean-style diet , its components and HF risk . Results : After adjustment for age , sex and energy intake , a 2-unit increment in the tMED was associated with 26 % lower risk of HF ( HR ( 95 % confidence interval ( CI ) ) : 0.76 ( 0.60–0.97 ) ) . After multivariable adjustment , this association was slightly attenuated and lost significance [ HR ( 95%CI ) : 0.82 ( 0.64–1.05 ) ] . Interestingly , we observed a significant association in multivariable adjusted models when milk products were excluded from the score ( HR ( 95 % CI ) : 0.75 ( 0.59–0.96 ) ) . Three score components were significantly associated with HF risk : alcohol ( HR ( 95%CI ) : 0.73 ( 0.55–0.97 ) for moderate versus low/high intakes ) , meat : 2.04 ( 1.17–3.55 ) and fish : 0.59 ( 0.36–0.95 ) , both for the highest versus the lowest quintile . Conclusions : The tMED was not significantly associated with HF risk , but low meat , high fish and moderate alcohol intake were inversely associated with HF risk in our non-Mediterranean population . Minor dietary changes could be valuable primary prevention measures , particularly the increase of fish consumption while reducing the intake of meat Previous studies have reported that high fat feeding in mild to moderate heart failure ( HF ) results in the preservation of contractile function . Recent evidence has suggested that preventing the switch from fatty acid to glucose metabolism in HF may ameliorate dysfunction , and insulin resistance is one potential mechanism for regulating substrate utilization . This study was design ed to determine whether peripheral and myocardial insulin resistance exists with HF and /or a high-fat diet and whether myocardial insulin signaling was altered accordingly . Rats underwent coronary artery ligation ( HF ) or sham surgery and were r and omized to normal chow ( NC ; 14 % kcal from fat ) or a high-fat diet ( SAT ; 60 % kcal from fat ) for 8 wk . HF + SAT animals showed preserved systolic ( + dP/dt and stroke work ) and diastolic ( -dP/dt and time constant of relaxation ) function compared with HF + NC animals . Glucose tolerance tests revealed peripheral insulin resistance in sham + SAT , HF + NC , and HF + SAT animals compared with sham + NC animals . PET imaging confirmed myocardial insulin resistance only in HF + SAT animals , with an uptake ratio of 2.3 ± 0.3 versus 4.6 ± 0.7 , 4.3 ± 0.4 , and 4.2 ± 0.6 in sham + NC , sham + SAT , and HF + NC animals , respectively ; the myocardial glucose utilization rate was similarly decreased in HF + SAT animals only . Western blot analysis of insulin signaling protein expression was indicative of cardiac insulin resistance in HF + SAT animals . Specifically , alterations in Akt and glycogen synthase kinase-3β protein expression in HF + SAT animals compared with HF + NC animals may be involved in mediating myocardial insulin resistance . In conclusion , HF animals fed a high-saturated fat exhibited preserved myocardial contractile function , peripheral and myocardial insulin resistance , decreased myocardial glucose utilization rates , and alterations in cardiac insulin signaling . These results suggest that myocardial insulin resistance may serve a cardioprotective function with high fat feeding in mild to moderate HF Objective To investigate enteral nutrition ’s effect on serum inflammatory factors and the cardiac function of malnourished elderly patients with heart failure . Patients and methods A total of 105 elderly patients with heart failure were r and omly divided into 3 groups : Treatment Group A , Treatment Group B , and the Control Group ( Group C ) , each group having 35 patients and being administered conventional heart failure treatment . Group A was treated with 500 mL·d−1 of enteral nutrition for 1 month . Group B was given the same dose of enteral nutrition for 3 months . The Control Group was given free diet . Nutritional risk screening 2002 was used to assess the nutritional status before and after the treatment for each group . New York Heart Association status was recorded as were left ventricular ejection fraction , plasma B-type natriuretic peptide , inteleukin-6 , C-reactive protein , and tumor necrosis factor-α . Results After the treatment , the body mass index , skinfold thickness of upper arm triceps , muscle circumference of the upper arm , upper arm muscle circumference , total protein , albumin , hemoglobin , and left ventricular ejection fraction in the treatment groups all increased , with relatively obvious relief of symptoms of heart failure . The levels of B-type natriuretic peptide , interleukin-6 , tumor necrosis factor-α , and C-reactive protein all rose to different extents ( P<0.05 ) and Treatment Group B showed more obvious improvement ( P<0.01 ) . Differences shown by the Control Group in each nutrition indicator , serum levels of inflammatory factors , and cardiac function had no statistical significance ( P>0.05 ) . Conclusion The use of enteral nutrition in conventional treatment of elderly patients with heart failure could improve not only patients ’ nutritional status and cardiac function , but also their immune function , thus reducing the levels of inflammatory factors . The longer the treatment period is , the more obvious the improvement in patients ’ cardiac function and inflammatory factors will be observed OBJECTIVES This study sought to investigate the effect of a multiple micronutrient supplement on left ventricular ejection fraction ( LVEF ) in patients with heart failure . BACKGROUND Observational studies suggest that patients with heart failure have reduced intake and lower concentrations of a number of micronutrients . However , there have been very few intervention studies investigating the effect of micronutrient supplementation in patients with heart failure . METHODS This was a r and omized , double-blind , placebo-controlled , parallel-group study involving 74 patients with chronic stable heart failure that compared multiple micronutrient supplementation taken once daily versus placebo for 12 months . The primary endpoint was LVEF assessed by cardiovascular magnetic resonance imaging or 3-dimensional echocardiography . Secondary endpoints were Minnesota Living With Heart Failure Question naire score , 6-min walk test distance , blood concentrations of N-terminal prohormone of brain natriuretic peptide , C-reactive protein , tumor necrosis factor alpha , interleukin-6 , interleukin-10 , and urinary levels of 8-iso-prostagl and in F2 alpha . RESULTS Blood concentrations of a number of micronutrients increased significantly in the micronutrient supplement group , indicating excellent compliance with the intervention . There was no significant difference in mean LVEF at 12 months between treatment groups after adjusting for baseline ( mean difference : 1.6 % , 95 % confidence interval : -2.6 to 5.8 , p = 0.441 ) . There was also no significant difference in any of the secondary endpoints at 12 months between treatment groups . CONCLUSIONS This study provides no evidence to support the routine treatment of patients with chronic stable heart failure with a multiple micronutrient supplement . ( Micronutrient Supplementation in Patients With Heart Failure [ MINT-HF ] ; NCT01005303 ) In animals , carbohydrate and fat composition during dietary interventions influenced cardiac metabolism , structure , and function . Because reduced-carbohydrate and reduced-fat hypocaloric diets are commonly used in the treatment of obesity , we investigated whether these interventions differentially affect left ventricular mass , cardiac function , and blood pressure . We r and omized 170 overweight and obese subjects ( body mass index , 32.9±4.4 ; range , 26.5–45.4 kg/m2 ) to 6-month hypocaloric diets with either reduced carbohydrate intake or reduced fat intake . We obtained cardiac MRI and ambulatory blood pressure recordings over 24 hours before and after 6 months . Ninety subjects completing the intervention period had a full cardiac MRI data set . Subjects lost 7.3±4.0 kg ( 7.9±3.8 % ) with reduced-carbohydrate diet and 6.2±4.2 kg ( 6.7±4.4 % ) with reduced-fat diet ( P<0.001 within each group ; P = not significant between interventions ) . Caloric restriction led to similar significant decreases in left ventricular mass with low-carbohydrate diets ( 5.4±5.4 g ) or low-fat diets ( 5.2±4.8 g ; P<0.001 within each group ; P = not significant between interventions ) . Systolic and diastolic left ventricular function did not change with either diet . The 24-hour systolic blood pressure decreased similarly with both interventions . Body weight change ( & bgr;=0.33 ; P=0.02 ) and percentage of ingested n-3 polyunsaturated fatty acids ( & bgr;=−0.27 ; P=0.03 ) predicted changes in left ventricular mass . In conclusion , weight loss induced by reduced-fat diets or reduced-carbohydrate diets similarly improved left ventricular mass in overweight and obese subjects over a 6-month period . However , n-3 polyunsaturated fatty acid ingestion may have an independent beneficial effect on left ventricular mass BACKGROUND AND AIMS Hospitalized patients with heart failure who are malnourished present a worse prognosis than those with an adequate nutritional status . We undertook this study to assess whether a nutritional intervention in malnourished hospitalized patients with heart failure benefits morbidity and mortality . METHODS A multicenter , r and omized , controlled clinical trial was conducted . A total of 120 malnourished hospitalized patients due to acute heart failure were r and omised to conventional heart failure treatment or conventional heart failure treatment combined with an individualized nutritional intervention . The primary endpoint of this study was a composite of all-cause death or readmission for worsening of HF , with a maximum follow-up of 12 months . Analysis was by intention to treat . RESULTS Recruitment was stopped early according to the study protocol after completing the follow-up of the first 120 patients enrolled ( 59 in the intervention group and 61 in the control group ) . Both groups were homogeneous in baseline characteristics . At 12 months , the primary outcome occurred in 27.1 % of patients in the intervention group and in 60.7 % of patients in the control group ( hazard ratio 0.45 ; 95 % confidence interval [ CI ] , 0.19 - 0.62 , p = 0.0004 ) . In total , 20.3 % of patients died in the intervention group and 47.5 % in the control group ( hazard ratio 0.37 , 95 % CI , 0.19 - 0.72 , p = 0.003 ) . Readmission due to heart failure was also lower in the intervention group ( 10.2 vs. 36.1 % , p = 0.001 ) . CONCLUSION Nutritional intervention in malnourished hospitalized patients with heart failure reduces the risk of death from any cause and the risk of readmission for worsening of heart failure ( Clinical Trial.govNCT01472237 ) Background Optimal macronutrient distribution of weight loss diets has not been established . The distribution of energy from carbohydrate and fat has been observed to promote differential plasma lipid responses in previous weight loss studies , and insulin resistance status may interact with diet composition and affect weight loss and lipid responses . Methods and Results Overweight and obese women ( n=245 ) were enrolled in a 1‐year behavioral weight loss intervention and r and omly assigned to 1 of 3 study groups : a lower fat ( 20 % energy ) , higher carbohydrate ( 65 % energy ) diet ; a lower carbohydrate ( 45 % energy ) , higher fat ( 35 % energy ) diet ; or a walnut‐rich , higher fat ( 35 % energy ) , lower carbohydrate ( 45 % energy ) diet . Blood sample s and data available from 213 women at baseline and at 6 months were the focus of this analysis . Triglycerides , total cholesterol , and high‐ and low‐density lipoprotein cholesterol were quantified and compared between and within groups . Triglycerides decreased in all study arms at 6 months ( P<0.05 ) . The walnut‐rich diet increased high‐density lipoprotein cholesterol more than either the lower fat or lower carbohydrate diet ( P<0.05 ) . The walnut‐rich diet also reduced low‐density lipoprotein cholesterol in insulin‐sensitive women , whereas the lower fat diet reduced both total cholesterol and high‐density lipoprotein cholesterol in insulin‐sensitive women ( P<0.05 ) . Insulin sensitivity and C‐reactive protein levels also improved . Conclusions Weight loss was similar across the diet groups , although insulin‐sensitive women lost more weight with a lower fat , higher carbohydrate diet versus a higher fat , lower carbohydrate diet . The walnut‐rich , higher fat diet result ed in the most favorable changes in lipid levels . Clinical Trial Registration URL : http://www . clinical trials.gov . Unique identifier : NCT01424007 Lipid accumulation in nonadipose tissue due to enhanced circulating fatty acids may play a role in the pathophysiology of heart failure , obesity , and diabetes . Accumulation of myocardial lipids and related intermediates , e.g. , ceramide , is associated with decreased contractile function , mitochondrial oxidative phosphorylation , and electron transport chain ( ETC ) complex activities . We tested the hypothesis that the progression of heart failure would be exacerbated by elevated myocardial lipids and an associated ceramide-induced inhibition of mitochondrial oxidative phosphorylation and ETC complex activities . Heart failure ( HF ) was induced by coronary artery ligation . Rats were then r and omly assigned to either a normal ( 10 % kcal from fat ; HF , n = 8) or high saturated fat diet ( 60 % kcal from saturated fat ; HF + Sat , n = 7 ) . Sham-operated animals ( sham ; n = 8) were fed a normal diet . Eight weeks postligation , left ventricular ( LV ) function was assessed by echocardiography and catheterization . Subsarcolemmal and interfibrillar mitochondria were isolated from the LV . Heart failure result ed in impaired LV contractile function [ decreased percent fractional shortening and peak rate of LV pressure rise and fall ( + /-dP/dt ) ] and remodeling ( increased end-diastolic and end-systolic dimensions ) in HF compared with sham . No further progression of LV dysfunction was evident in HF + Sat . Mitochondrial state 3 respiration was increased in HF + Sat compared with HF despite elevated myocardial ceramide . Activities of ETC complexes II and IV were elevated in HF + Sat compared with HF and sham . High saturated fat feeding following coronary artery ligation was associated with increased oxidative phosphorylation and ETC complex activities and did not adversely affect LV contractile function or remodeling , despite elevations in myocardial ceramide BACKGROUND The Dietary Approaches to Stop Hypertension ( DASH ) diet effectively reduces blood pressure . In observational studies , the association between diets consistent with DASH and risk of coronary heart disease and stroke has been examined with varying results . We hypothesized that diets consistent with the DASH diet would be associated with a lower incidence of heart failure ( HF ) . METHODS We conducted a prospect i ve observational study in 36 019 participants in the Swedish Mammography Cohort who were aged 48 to 83 years and without baseline HF , diabetes mellitus , or myocardial infa rct ion . Diet was measured using food-frequency question naires . We created a score to assess consistency with the DASH diet by ranking the intake of DASH diet components and 3 additional scores based on food and nutrient guidelines . Cox proportional hazards models were used to calculate rate ratios of HF-associated hospitalization or death , determined using the Swedish inpatient and cause-of-death registers between January 1 , 1998 , and December 31 , 2004 . RESULTS During 7 years , 443 women developed HF . Women in the top quartile of the DASH diet score based on ranking DASH diet components had a 37 % lower rate of HF after adjustment for age , physical activity , energy intake , education status , family history of myocardial infa rct ion , cigarette smoking , postmenopausal hormone use , living alone , hypertension , high cholesterol concentration , body mass index ( calculated as weight in kilograms divided by height in meters squared ) , and incident myocardial infa rct ion . Rate ratios ( 95 % confidence intervals ) across quartiles were 1 [ Reference ] , 0.85 ( 0.66 - 1.11 ) , 0.69 ( 0.54 - 0.88 ) , and 0.63 ( 0.48 - 0.81 ) ; P(trend ) < .001 . A similar pattern was seen for the guideline -based scores . CONCLUSION In this population , diets consistent with the DASH diet are associated with lower rates of HF The prevalence of cardiac cachexia in chronic heart failure is approximately 5 % to 15 % and 18-month mortality rates can reach 50 % . Treatment with angiotensin-converting enzyme inhibitors and beta-blockers may confer some benefit but no proven therapy exists . We tested the effects of an oral nutritional supplement in cachectic patients with heart failure . This was a prospect i ve , r and omized , double-blind , placebo-controlled pilot study which r and omized 29 patients to a high-caloric ( 600 kcal ) high-protein ( 20 g ) oral nutritional supplement or placebo for a duration of 6 weeks in addition to the patients ’ usual food intake . At baseline , 6 weeks , and 18 weeks , we measured body weight , quality of life , body composition , heart function , laboratory parameters , and exercise performance . Edema-free body weight increased in 19 of 20 patients receiving intervention at 6 weeks and in 17 of 19 patients at 18 weeks with an average weight gain of 2.0 ± 1.7 kg ( 3.1 ± 2.4 % , p = 0.0001 ) and 2.3 ± 3.1 kg ( 3.6 ± 4.7 % , p = 0.007 ) at 6 and 18 weeks , respectively . Most of the weight gain was fat tissue with an absolute gain of 1.5 ± 1.7 kg ( p = 0.003 ) and 1.6 ± 2.7 kg ( p = 0.008 ) . A significant improvement in quality of life and decrease in serum levels of tumor necrosis factor-α were observed ( p < 0.05 for both ) . We demonstrated the feasibility of oral nutritional supplement in cachectic patients with heart failure and significant clinical benefit in terms of body size and body composition , laboratory parameters , and quality of life ( www . clinical trials.gov identifier NCT00654719 ) INTRODUCTION Nutritional therapy in heart failure ( HF ) patients has been focused on fluid and sodium restriction with the aim of decreasing volume overload . However , these recommendations are not well established and sometimes controversial . OBJECTIVE To evaluate the effect of the consumption of a low-carbohydrate diet on oxygen saturation , body composition and clinical variables during two months of follow-up in chronic , stable heart failure patients . METHODS In a parallel group r and omized controlled clinical trial , 88 ambulatory patients were r and omly assigned to a low-carbohydrate diet group ( 40 % carbohydrates , 20 % protein and 40 % fats [ 12 % saturated , 18 % monounsaturated and 10 % polyunsaturated ] ) or a st and ard diet group ( 50 % carbohydrates , 20 % protein and 30 % fats [ 10 % saturated , 10 % monounsaturated and 10 % polyunsaturated ] ) for two months . Diets were normocaloric in both groups . At baseline and at two months of follow-up , the variables evaluated were : oxygen saturation , dietary intake , body composition and h and grip strength . RESULTS After two months of follow-up , the low-carbohydrate diet group decreased the carbohydrate consumption and had improved oxygen saturation ( 93.0 ±4.4 to 94.6 ± 3.2 , p = 0.02 ) , while the st and ard diet group had decreased ( 94.90 ± 2.4 to 94.0 ± 2.9 , p = 0.03 ) . There were also differences between the groups at the end of the study ( p = 0.04 ) . No significant differences showed in h and grip strength in both groups , low-carbohydrate diet group ( 26.4 ± 8.3 to 27.2 ± 8.3 kg , p = 0.07 ) and st and ard diet group ( 25.4 ± 8.9 to 26.1 ± 9.5 kg , p = 0.14 ) . CONCLUSIONS Low-carbohydrate diet may improve the oxygen saturation in patients with chronic stable heart failure OBJECTIVE Dietary strategies in heart failure ( HF ) are focused on sodium and fluid restriction to minimize the risk for acute volume overload episodes . However , the importance of dietary factors beyond sodium intake in the prognosis of the disease is uncertain . The purpose of this study was to evaluate the association of macro- and micronutrients intake on 1-y mortality in patients with HF . METHODS A secondary analysis of 203 patients with chronic HF enrolled in a r and omized trial of sodium reduction was completed . Patients with a complete 3-d food record at baseline were included in this analysis ( N = 118 ) ; both control and intervention arms were combined . Three-d mean dietary intake was estimated . Cox multivariable regression analysis was used to evaluate the association between dietary factors and 1-y mortality . RESULTS Among the 118 included patients , 54 % were men , median ( 25th-75th percentiles ) age 66 y ( 52 - 75 y ) , median ejection fraction 45 % ( 30%-60 % ) , and ischemic etiology present in 49 % of patients . The association with 1-y mortality was significant for both polyunsaturated fatty acids ( PUFA ; adjusted hazard ratio [ HR ] , 0.67 ; 95 % confidence interval [ CI ] . 0.51 - 0.86 for intake as percentage of daily energy ) and saturated fatty acids ( SFA ; adjusted HR , 1.15 ; 95 % CI , 1.03 - 1.30 for intake as percentage of daily energy ) . Median of intake as percentage of daily energy was 5.3 % for PUFAs and 8.2 % for SFAs . CONCLUSIONS Intake of PUFAs and SFAs was independently associated with 1-y all-cause mortality in patients with chronic HF . Limiting dietary SFA and increasing PUFA intake may be advisable in this population BACKGROUND Hospitalized , malnourished older adults have a high risk of readmission and mortality . OBJECTIVE Evaluation of a high-protein oral nutritional supplement ( HP-HMB ) containing beta-hydroxy-beta-methylbutyrate on postdischarge outcomes of nonelective readmission and mortality in malnourished , hospitalized older adults . DESIGN Multicenter , r and omized , placebo-controlled , double-blind trial . SETTING Inpatient and posthospital discharge . PATIENTS Older ( ≥65 years ) , malnourished ( Subjective Global Assessment [ SGA ] class B or C ) adults hospitalized for congestive heart failure , acute myocardial infa rct ion , pneumonia , or chronic obstructive pulmonary disease . INTERVENTIONS St and ard-of-care plus HP-HMB ( n = 328 ) or a placebo supplement ( n = 324 ) , 2 servings/day . MEASUREMENTS Primary composite endpoint was 90-day postdischarge incidence of death or nonelective readmission . Other endpoints included 30- and 60-day postdischarge incidence of death or readmission , length of stay ( LOS ) , SGA class , body weight , and activities of daily living ( ADL ) . RESULTS The primary composite endpoint was similar between HP-HMB ( 26.8 % ) and placebo ( 31.1 % ) . No between-group differences were observed for 90-day readmission rate , but 90-day mortality was significantly lower with HP-HMB relative to placebo ( 4.8 % vs. 9.7 % ; relative risk 0.49 , 95 % confidence interval [ CI ] , 0.27 to 0.90 ; p = 0.018 ) . The number-needed-to-treat to prevent 1 death was 20.3 ( 95 % CI : 10.9 , 121.4 ) . Compared with placebo , HP-HMB result ed in improved odds of better nutritional status ( SGA class , OR , 2.04 , 95 % CI : 1.28 , 3.25 , p = 0.009 ) at day 90 , and an increase in body weight at day 30 ( p = 0.035 ) . LOS and ADL were similar between treatments . LIMITATIONS Limited generalizability ; patients represent a selected hospitalized population . CONCLUSIONS Although no effects were observed for the primary composite endpoint , compared with placebo HP-HMB decreased mortality and improved indices of nutritional status during the 90-day observation period . CLINICAL TRIAL REGISTRATION www . Clinical Trials.govNCT01626742 Background : Patients with heart failure ( HF ) commonly have unintentional weight loss , depressive symptoms , and elevated levels of high-sensitivity C-reactive protein ( hsCRP ) . Each of these variables has been independently associated with shorter cardiac event – free survival . However , little data exist on the relationships of unintentional weight loss , hsCRP level , and depressive symptoms to cardiac event – free survival . Objective : The aims of this study were to determine ( 1 ) whether depressive symptoms and elevated hsCRP level predicted unintentional weight loss and ( 2 ) whether unintentional weight loss predicted shorter cardiac event – free survival . Methods : This was a prospect i ve study of 243 consecutive HF patients ( 61 % men , 61 ± 14 years old ) enrolled during an index hospitalization for HF exacerbation . Patients provided blood sample s to measure hsCRP level and completed the Beck Depression Inventory to assess depressive symptoms at discharge . Body weight was measured at discharge and 6 months later . Unintentional weight loss was defined as weight loss of greater than 6 % of body weight since discharge . Cardiac event – free survival was followed for 1 year after the second measurement of body weight through monthly telephone interviews . Hierarchical logistic regression was used to determine whether depressive symptoms and elevated hsCRP level predicted unintentional weight loss . Cox hazard regression was used to determine whether unintentional weight loss predicted cardiac event – free survival . Results : Thirty-five patients ( 14.4 % ) experienced unintentional weight loss at 6 months after discharge . Hierarchical Cox hazard regression revealed that patients with unintentional weight loss had a 3.2 times higher risk for cardiac events , adjusting for other clinical factors ( P < .001 ) . In hierarchical logistic regression , elevated hsCRP level ( odds ratio , 1.49 ; 95 % confidence interval , 1.15–1.92 ) and depressive symptoms ( odds ratio , 1.07 , 95 % confidence interval , 1.02–1.12 ) independently predicted unintentional weight loss . Conclusions : Unintentional weight loss was an independent predictor of poor outcomes . Heart failure patients with depressive symptoms and elevated hsCRP levels are at a higher risk for unintentional weight loss OBJECTIVES The authors sought to evaluate clinical outcomes of patients after an episode of acute heart failure ( AHF ) according to their adherence to the Mediterranean diet ( MedDiet ) . BACKGROUND It has been proved that MedDiet is a useful tool in primary prevention of cardiovascular diseases . However , it is unknown whether adherence to MedDiet is associated with better outcomes in patients who have already experienced an episode of AHF . METHODS We design ed a prospect i ve study that included consecutive patients diagnosed with AHF in 7 Spanish emergency departments ( EDs ) . Patients were included if they or their relatives were able to answer a 14-point score of adherence to the MedDiet , which classified patients as adherents ( ≥9 points ) or nonadherents ( ≤8 points ) . The primary endpoint was all-cause mortality at the end of follow-up , and secondary endpoints were 1-year ED revisit without hospitalization , rehospitalization , death , and a combined endpoint of all these variables for patients discharged after the index episode . Unadjusted and adjusted hazard ratios ( HRs ) were calculated . RESULTS We included 991 patients ( mean age of 80 ± 10 years , 57.8 % women ) ; 523 ( 52.9 % ) of whom were adherent to the MedDiet . After a mean follow-up period of 2.1 ± 1.3 years , no differences were observed in survival between adherent and nonadherent patients ( HR of adherents [ HRadh ] = 0.86 ; 95 % confidence interval [ CI ] : 0.73 to 1.02 ) . The 1-year cumulative ED revisit for the whole cohort was 24.5 % ( HRadh = 1.10 ; 95 % CI : 0.84 to 1.42 ) , hospitalization 43.7 % ( HRadh = 0.74 ; 95 % CI : 0.61 to 0.90 ) , death 22.7 % ( HRadh = 1.05 ; 95 % CI : 0.8 to 1.38 ) , and combined endpoint 66.8 % ( HRadh = 0.89 ; 95 % CI : 0.76 to 1.04 ) . Adjustment by age , hypertension , peripheral arterial disease , previous episodes of AHF , treatment with statins , air-room pulsioxymetry , and need for ventilation support in the ED rendered similar results , with no statistically significant differences in mortality ( HRadh = 0.94 ; 95 % CI : 0.80 to 1.13 ) and persistence of lower 1-year hospitalization for adherents ( HRadh = 0.76 ; 95 % CI : 0.62 to 0.93 ) . CONCLUSIONS Adherence to the MedDiet did not influence long-term mortality after an episode of AHF , but it was associated with decreased rates of rehospitalization during the next year AIMS The aim of this study was to evaluate the effect of the Mediterranean diet ( MedDiet ) on the incidence of heart failure ( HF ) , a pre-specified secondary outcome in the PREDIMED ( PREvención con DIeta MEDiterránea ) primary nutrition-intervention prevention trial . METHODS AND RESULTS Participants at high risk of cardiovascular disease were r and omly assigned to one of three diets : MedDiet supplemented with extra-virgin olive oil ( EVOO ) , MedDiet supplemented with nuts , or a low-fat control diet . Incident HF was ascertained by a Committee for Adjudication of events blinded to group allocation . Among 7403 participants without prevalent HF followed for a median of 4.8 years , we observed 29 new HF cases in the MedDiet with EVOO group , 33 in the MedDiet with nuts group , and 32 in the control group . No significant association with HF incidence was found for the MedDiet with EVOO and MedDiet with nuts , compared with the control group [ hazard ratio ( HR ) 0.68 ; 95 % confidence interval ( CI ) 0.41 - 1.13 , and HR 0.92 ; 95 % CI 0.56 - 1.49 , respectively ] . CONCLUSION In this sample of adults at high cardiovascular risk , the MedDiet did not result in lower HF incidence . However , this pre-specified secondary analysis may have been underpowered to provide valid conclusions . Further r and omized controlled trials with HF as a primary outcome are needed to better assess the effect of the MedDiet on HF risk . TRIAL REGISTRATION IS RCT N35739639 We investigated whether 30 days of oral supplementation with a special mixture of amino acids ( AAs ) , together with conventional therapy , could improve exercise capacity in elderly out patients with chronic heart failure ( CHF ) . A group of 95 out patients ( 12 women and 83 men ; New York Heart Association class II-III ) aged 65 - 74 years were studied . This was a r and omized , double-blind , placebo-controlled study . The patients performed a basal exercise test and were then r and omly assigned to a special oral nutritional mixture of AAs 4 g twice daily ( n = 43 ) or placebo ( n = 42 ) . After 30 days we repeated the exercise test . In both tests we measured the following : oxygen consumption ( VO2 ) , CO2 production ( VCO2 ) , minute ventilation ( VE ) , oxygen cost of ventilation ( VO2/VE ) , CO2 elimination per liter of ventilation ( VCO2/VE ) , respiratory exchange ratio ( RER ; calculated as VCO2/VO2 ) , oxygen pulse ( VO2/heart rate [ HR ] ) and anaerobic metabolism during exercise ( ANA-VO2 ) . At day 30 , exercise capacity in the AA group had improved ( + 11 + /- 8 W , p < 0.01 ; + 67.5 + /- 44 seconds , p < 0.02 ) . This improvement was associated with both reduced circulatory dysfunction and increased peripheral oxygen availability . Indeed , peak VO2 increased by 1.2 + /- 1.1 mL/kg per min ( + 12.7 % + /- 13 % ; p<0.02 ) and VO2/HR improved by 1.5 + /- 1.4 mL O2 per heartbeat ( p < 0.05 ) . ANA-VO2 was reduced by > 50 % in patients on AAs ( from 20.2 + /- 10 mL/kg at day 0 to 10.9 + /- 5 mL/kg at day 30 ; p < 0.02 ) . These variables did not significantly change for patients who received placebo . In conclusion , the study showed that oral AA supplementation , in conjunction with st and ard pharmacologic therapy , appears to increase exercise capacity by improving circulatory function , muscle oxygen consumption , and aerobic production of energy in elderly out patients with CHF OBJECTIVE Obesity is an independent risk factor for the development of heart failure , and the two commonly co-exist . The European Society of Cardiology does not provide guidance regarding weight loss strategies in heart failure . The aim of this study was to systematic ally review the evidence for outcomes following intentional weight loss in patients with heart failure and obesity . METHOD A systematic review of English articles was undertaken using data bases PubMed , Embase and CENTRAL . R and omized controlled trials and observational studies reporting outcomes following intentional weight loss by lifestyle , surgical or pharmacotherapy intervention in patients with obesity and heart failure were included . RESULTS Four r and omized controlled trials and seven observational studies were identified . Two r and omized controlled trials used diet and exercise as an intervention , one used diet alone and one used a pharmacological intervention ( orlistat ) . All but one reported significant weight loss . Two reported improvement in exercise capacity and quality of life . One reported improvement in New York Heart Association functional class in heart failure with preserved ejection fraction . The observational studies , five of which reported on outcomes following bariatric surgery , despite being small , heterogeneous and high risk of bias , suggested a trend in improvement of left ventricular function , quality of life and exercise capacity following weight loss . CONCLUSION Weight loss is achievable with lifestyle intervention in those with heart failure and obesity and may result in improvements in New York Heart Association classification , quality of life and exercise capacity Growing evidence has emerged about the role of dietary patterns and components in heart failure ( HF ) incidence and severity . The objective here is to provide a comprehensive summary of the current evidence regarding dietary patterns/components and HF . A comprehensive search of online data bases was conducted using multiple relevant keywords to identify relevant human studies . The Dietary Approaches to Stop Hypertension ( DASH ) and Mediterranean diets have consistently been associated with decreased HF incidence and severity . Regarding specific dietary components , fruit , vegetables , legumes and whole grains appear beneficial . Current evidence suggests that red/processed meats , eggs and refined carbohydrates are harmful , while fish , dairy products and poultry remain controversial . However , there is a notable lack of human intervention trials . The existing but limited observational and interventional evidence from human studies suggests that a plant-based dietary pattern high in antioxidants , micronutrients , nitrate and fibre but low in saturated/trans-fat and Na may decrease HF incidence/severity . Potential mechanisms include decreased oxidative stress , homocysteine and inflammation but higher antioxidant defence and NO bioavailability and gut microbiome modulation . R and omised , controlled trials are urgently required BACKGROUND Findings from the Look AHEAD trial showed no significant reductions in the primary outcome of cardiovascular disease incidence in adults with type 2 diabetes r and omly assigned to an intensive lifestyle intervention for weight loss compared with those r and omly assigned to diabetes support and education ( control ) . We examined whether the incidence of cardiovascular disease in Look AHEAD varied by changes in weight or fitness . METHODS Look AHEAD was a r and omised clinical trial done at 16 clinical sites in the USA , recruiting patients from Aug 22 , 2001 , to April 30 , 2004 . In the trial , 5145 overweight or obese adults aged 45 - 76 years with type 2 diabetes were assigned ( 1:1 ) to an intensive lifestyle intervention or diabetes support and education . In this observational , post-hoc analysis , we examined the association of magnitude of weight loss and fitness change over the first year with incidence of cardiovascular disease . The primary outcome of the trial and of this analysis was a composite of death from cardiovascular causes , non-fatal acute myocardial infa rct ion , non-fatal stroke , or admission to hospital for angina . The secondary outcome included the same indices plus coronary artery bypass grafting , carotid endartectomy , percutaneous coronary intervention , hospitalisation for congestive heart failure , peripheral vascular disease , or total mortality . We adjusted analyses for baseline differences in weight or fitness , demographic characteristics , and risk factors for cardiovascular disease . The Look AHEAD trial is registered with Clinical Trials.gov , number NCT00017953 . FINDINGS For the analyses related to weight change , we excluded 311 ineligible participants , leaving a population of 4834 ; for the analyses related to fitness change , we excluded 739 participants , leaving a population of 4406 . In analyses of the full cohort ( ie , combining both study groups ) , over a median 10·2 years of follow-up ( IQR 9·5 - 10·7 ) , individuals who lost at least 10 % of their bodyweight in the first year of the study had a 21 % lower risk of the primary outcome ( adjusted hazard ratio [ HR ] 0·79 , 95 % CI 0·64 - 0·98 ; p=0·034 ) and a 24 % reduced risk of the secondary outcome ( adjusted HR 0·76 , 95 % CI 0·63 - 0·91 ; p=0·003 ) compared with individuals with stable weight or weight gain . Achieving an increase of at least 2 metabolic equivalents in fitness change was associated with a significant reduction in the secondary outcome ( adjusted HR 0·77 , 95 % CI 0·61 - 0·96 ; p=0·023 ) but not the primary outcome ( adjusted HR 0·78 , 0·60 - 1·03 ; p=0·079 ) . In analyses treating the control group as the reference group , participants in the intensive lifestyle intervention group who lost at least 10 % of their bodyweight had a 20 % lower risk of the primary outcome ( adjusted HR 0·80 , 95 % CI 0·65 - 0·99 ; p=0·039 ) , and a 21 % lower risk of the secondary outcome ( adjusted HR 0·79 , 95 % CI 0·66 - 0·95 ; p=0·011 ) ; however , change in fitness was not significantly associated with a change in the primary outcome . INTERPRETATION The results of this post-hoc analysis of Look AHEAD suggest an association between the magnitude of weight loss and incidence of cardiovascular disease in people with type 2 diabetes . These findings suggest a need to continue to refine approaches to identify individuals who are most likely to benefit from lifestyle interventions and to develop strategies to improve the magnitude of sustained weight loss with lifestyle interventions . FUNDING US National Institute of Diabetes and Digestive and Kidney Diseases There is ample research to support the potential benefits of a high protein diet on clinical outcomes in overweight/obese , diabetic subjects . However , nutritional management of overweight/obese individuals with heart failure ( HF ) and type 2 diabetes mellitus ( DM ) or metabolic syndrome ( MS ) is poorly understood and few clinical guidelines related to nutritional approaches exist for this subgroup . This article describes the design , methods , and baseline characteristics of study participants enrolled in Pro-HEART , a r and omized clinical trial to determine the short term and long term effects of a high protein diet ( 30 % protein [ ~110 g/day ] , 40 % carbohydrates [ 150 g/day ] , 30 % fat [ ~50 g/day ] ) versus a st and ard protein diet ( 15 % protein [ ~55 g/day ] , 55 % carbohydrates [ ~200 g/day ] , 30 % fat [ ~50 g/day ] ) on body weight and adiposity , cardiac structure and function , functional status , lipid profile , glycemic control , and quality of life . Between August , 2009 and May , 2013 , 61 individuals agreed to participate in the study ; 52 ( 85 % ) - mean age 58.2 ± 9.8 years ; 15.4 % Blacks ; 57.7 % Whites ; 19.2 % Hispanics ; 7.7 % Asians ; 73.1 % male ; weight 112.0 ± 22.6 kg - were r and omized to a 3-month intensive weight management program of either a high protein or st and ard protein diet ; data were collected at baseline , 3 months , and 15 months . This study has the potential to reveal significant details about the role of macronutrients in weight management of overweight/obese individuals with HF and DM or MS |
1,295 | 26,607,294 | Concordance between these two population s was found for some SNPs . | This systematic review investigates the high level of hypertension found among urban dwellers in West Africa and in the West African Diaspora in the Americas in relation to variants within the genes encoding the renin angiotensinogen system . | The frequency of the 235 T and 174 M alleles of the angiotensinogen gene , previously reported to be associated with hypertension in Caucasians and Japanese , was compared between 57 hypertensive African Americans and 130 normotensive African Americans sample d as part of a community survey of hypertension in the Chicago area . The frequency of the 235 T allele was unrelated to hypertension status ( cases , 83 % , control subjects , 82 % ) , as was true for the 174 M allele . Compared with Caucasians , the frequency of the 235 T allele was twice as high in this African American population , while the frequency of the 174 M allele was similar . Even higher frequencies of the 235 T allele ( 93 % ) were noted in a sample of 122 Nigerians . It appears that the 235 T allele is very common in population s of West African origin , although we found no evidence that it confers risk of hypertension Abstract —The genes of the renin-angiotensin system have been subjected to intense molecular scrutiny in cardiovascular disease studies , but their contribution to risk is still uncertain . In this study , we sample d 192 African American and 153 European American families ( 602 and 608 individuals , respectively ) to evaluate the contribution of variations in genes that encode renin-angiotensin system components of susceptibility to hypertension . We genotyped 25 single-nucleotide polymorphisms in the renin-angiotensin system genes ACE , AGT , AGTR1 , and REN . The family-based transmission/disequilibrium test was performed with each single-nucleotide polymorphism and with the multilocus haplotypes . Two individual single-nucleotide polymorphisms were significantly associated with hypertension among African Americans , and this result persisted when both groups were combined . The associations were confirmed in haplotype analysis for REN , AGTR1 , and ACE in African Americans . Consistent but less significant evidence was found in European Americans . We also r and omly sample d unrelated individuals across families to obtain 84 cases and 108 controls among the African Americans and 41 cases and 113 controls in the European Americans . Single-nucleotide polymorphism and haplotype analyses again showed consistent , albeit weaker , results . Thus , in this biracial population sample , we find evidence that interindividual variation in the renin-angiotensin system genes contributes to hypertension risk BACKGROUND The angiotensin II type 1 receptor A1166C polymorphism has been associated with increased risks of hypertension and myocardial infa rct ion in several small studies . We examined the association between this polymorphism and new-onset hypertension , blood pressure ( BP ) control , and incident cardiovascular events in a large population -based cohort of older adults . METHODS Eight hundred self-identified African Americans and 1,371 r and omly selected white participants in the Cardiovascular Health Study were genotyped . The median duration of follow-up was 8.1 years . RESULTS The A1166C polymorphism was not associated with new-onset hypertension , with BP control , or with incident cardiovascular events in the overall population . In white participants , the CC genotype was associated with higher baseline systolic BP and pulse pressure , compared to the AC or AA genotype . In whites with treated hypertension at baseline , compared to the AA genotype , the CC genotype was associated with increased risks of incident congestive heart failure ( hazard ratio = 2.5 , 95 % confidence interval [ CI ] 1.3 - 4.9 ) and incident ischemic stroke ( hazard ratio = 2.6 , 95 % CI 1.1 - 6.0 ) . These associations were not observed among white participants without treated hypertension , but the interaction of genotype with treated hypertension on ischemic stroke and heart failure was only marginally significant . CONCLUSIONS On the whole , in this large cohort of older adults , the A1166C polymorphism was not associated with BP control or incident cardiovascular events . The subgroup findings in treated hypertensives need to be confirmed in additional studies |
1,296 | 29,377,473 | Meta-regression analyses showed that risk of NODM was not associated with baseline age , baseline body mass index ( BMI ) , proportion of men , treatment duration or percent LDL cholesterol reduction .
CONCLUSIONS Alirocumab and evolocumab , two types of PCSK9-mAb approved by the US Food and Drug Administration and the European Medicines Agency , had no significant impact on NODM and glucose homeostasis , regardless of PCSK9-mAb type , participant characteristics , treatment duration , treatment method and differences in control treatment .
Baseline age , BMI , proportion of men , treatment duration , and percent change of LDL cholesterol did not influence diabetes risk | AIMS To investigate the effect of two clinical ly applied proprotein convertase subtilisin/kexin type 9 monoclonal antibodies ( PCSK9-mAbs ) on glycaemia and new-onset diabetes mellitus ( NODM ) . | Purpose Even with statins and other lipid-lowering therapy ( LLT ) , many patients with heterozygous familial hypercholesterolemia ( heFH ) continue to have elevated low-density lipoprotein cholesterol ( LDL-C ) levels . ODYSSEY HIGH FH ( NCT01617655 ) assessed the efficacy and safety of alirocumab , a proprotein convertase subtilisin/kexin type 9 monoclonal antibody , versus placebo in patients with heFH and LDL-C ≥ 160 mg/dl despite maximally tolerated statin ± other LLT . Methods Patients were r and omized to subcutaneous alirocumab 150 mg or placebo every 2 weeks ( Q2W ) for 78 weeks . The primary endpoint was percent change in LDL-C from baseline to week 24 . Results Mean baseline LDL-C levels were 196.3 mg/dl in the alirocumab ( n = 71 ) and 201.0 mg/dl in the placebo groups ( n = 35 ) . Significant mean ( st and ard error [ SE ] ) reductions in LDL-C from baseline to week 24 were observed with alirocumab ( −45.7 [ 3.5 ] % ) versus placebo ( −6.6 [ 4.9 ] % ) , a difference of −39.1 ( 6.0 ) % ( P < 0.0001 ) . Absolute mean ( SE ) LDL-C levels were reduced from baseline by 90.8 ( 6.7 ) mg/dl with alirocumab at week 24 , with reductions maintained to week 78 . Treatment-emergent adverse events were generally comparable between groups . Injection-site reactions were more frequent in the alirocumab group ( 8.3 % ) versus placebo ( 5.7 % ) ; most were mild in severity and did not result in study medication discontinuation . Conclusions In patients with heFH and very high LDL-C baseline levels despite maximally tolerated statin ± other LLT , alirocumab 150 mg Q2W demonstrated significant reductions in LDL-C levels with 41 % of patients achieving predefined LDL-C goals . Alirocumab was generally well tolerated BACKGROUND Efficacy and safety of alirocumab were compared with ezetimibe in hypercholesterolemic patients at moderate cardiovascular risk not receiving statins or other lipid-lowering therapy . METHODS In a Phase 3 , r and omized , double-blind , double-dummy study ( NCT01644474 ) , patients ( low-density lipoprotein cholesterol [ LDL-C ] 100 - 190 mg/dL , 10-year risk of fatal cardiovascular events ≥ 1%-<5 % [ systemic coronary risk estimation ] ) were r and omized to ezetimibe 10mg/day ( n=51 ) or alirocumab 75 mg subcutaneously ( via 1-mL autoinjector ) every 2 weeks ( Q2W ) ( n=52 ) , with dose up-titrated to 150 mg Q2W ( also 1 mL ) at week 12 if week 8 LDL-C was ≥ 70 mg/dL. Primary endpoint was mean LDL-C % change from baseline to 24 weeks , analyzed using all available data ( intent-to-treat approach , ITT ) . Analyses using on-treatment LDL-C values were also conducted . RESULTS Mean ( SD ) baseline LDL-C levels were 141.1 ( 27.1 ) mg/dL ( alirocumab ) and 138.3 ( 24.5 ) mg/dL ( ezetimibe ) . The 24-week treatment period was completed by 85 % of alirocumab and 86 % of ezetimibe patients . Least squares mean ( SE ) LDL-C reductions were 47 (3)% with alirocumab versus 16 (3)% with ezetimibe ( ITT ; p<0.0001 ) and 54 (2)% versus 17 (2)% ( on-treatment ; p<0.0001 ) . At week 12 , before up-titration , alirocumab 75 mg Q2W reduced LDL-C by 53 (2)% ( on-treatment ) . Injection site reactions were infrequent ( < 2 % and < 4 % of alirocumab and ezetimibe patients , respectively ) . CONCLUSIONS Alirocumab demonstrated significantly greater LDL-C lowering versus ezetimibe after 24 weeks with the lower 75 mg Q2W dose sufficient to provide ≥ 50 % LDL-C reduction in the majority of the patients . Adverse events were comparable between groups BACKGROUND AND AIMS In previous phase III studies , the PCSK9 monoclonal antibody alirocumab was administered at doses of 75 or 150 mg every 2 weeks ( Q2W ) . CHOICE I ( NCT01926782 ) evaluated 300 mg every 4 weeks ( Q4W ) in patients on either maximally tolerated statin or no statin , both ± other lipid-lowering therapies . METHODS CHOICE I included patients with hypercholesterolemia at moderate-to-very-high cardiovascular risk . Patients were r and omized to alirocumab 300 mg Q4W , 75 mg Q2W ( calibrator arm ) , or placebo for 48 weeks , with dose adjustment for either alirocumab arm to 150 mg Q2W at Week ( W ) 12 if at W8 LDL-C levels were > 70/100 mg/dL ( 1.8/2.6 mmol/L ) depending on cardiovascular risk or LDL-C reduction was < 30 % from baseline . Co- primary endpoints were percent LDL-C change from baseline to W24 , and to time-averaged LDL-C over W21 - 24 . RESULTS Approximately two-thirds of r and omized patients were receiving statins . At W12 , 14.7 % ( no statin ) and 19.3 % ( statin ) of patients receiving alirocumab 300 mg Q4W required dose adjustment . At W24 , significant LDL-C reductions from baseline were observed with alirocumab 300 mg Q4W : mean differences were -52.7 % ( no statin ; placebo : -0.3 % ) and -58.8 % ( statin ; placebo : -0.1 % ) . Average LDL-C reductions from baseline to W21 - 24 were also significantly greater with alirocumab 300 mg Q4W vs. placebo in patients not receiving ( -56.9 % vs. -1.6 % ) and receiving statin ( -65.8 % vs. -0.8 % ) . Treatment-emergent adverse event rates ranged from 61.1 to 75.0 % ( placebo ) and 71.5 to 78.1 % ( alirocumab 300 mg Q4W ) . CONCLUSIONS Alirocumab 300 mg Q4W is a viable additional treatment option in patients requiring LDL-C-lowering Aims Statins have modest adverse effects on glycaemic control . Alirocumab , a proprotein convertase subtilisin/kexin type 9 inhibitor , lowers low-density lipoprotein cholesterol . This study assessed the effects of alirocumab on new-onset diabetes and pre-diabetes incidence in individuals without diabetes at baseline . Methods and results Pooled analysis of 10 ODYSSEY Phase 3 trials ( n = 4974 ) of 24–104 weeks duration . Six trials ( n = 4211 ) were ≥52 weeks in length . Most patients received background maximally tolerated statin . Alirocumab effect on the rate of diabetes-related treatment-emergent adverse events ( TEAEs ) , and /or fasting plasma glucose ( FPG ) and glycated haemoglobin A1C ( HbA1C ) was measured at baseline and every 12–24 weeks . Transition to diabetes analysis combined TEAE and FPG/HbA1C laboratory data . At baseline , 30.7 % of individuals had diabetes and were excluded from the current analysis . The remaining 3448 individuals without diabetes had pre-diabetes ( 39.6 % ) or were normoglycaemic ( 29.7 % ) . The hazard ratio ( HR ; 95 % confidence interval ) for diabetes-related TEAEs in alirocumab was 0.64 ( 0.36–1.14 ) vs. placebo and 0.55 ( 0.22–1.41 ) vs. ezetimibe . The HR associated for transition from pre-diabetes to new-onset diabetes for alirocumab was 0.90 ( 0.63–1.29 ) vs. placebo and 1.10 ( 0.57–2.12 ) vs. ezetimibe . Mean change in FPG/HbA1C over time showed no difference between treatment groups in patients without diabetes . Conclusions There was no evidence of an effect of alirocumab on transition to new-onset diabetes in 3448 individuals without diabetes at baseline with a follow-up period of 6–18 months , compared to either placebo or ezetimibe . Longer follow-up with larger number of individuals is needed to conclusively rule out an effect Aims To assess long-term ( 78 weeks ) alirocumab treatment in patients with heterozygous familial hypercholesterolaemia ( HeFH ) and inadequate LDL-C control on maximally tolerated lipid-lowering therapy ( LLT ) . Methods and results In two r and omized , double-blind studies ( ODYSSEY FH I , n = 486 ; FH II , n = 249 ) , patients were r and omized 2 : 1 to alirocumab 75 mg or placebo every 2 weeks ( Q2W ) . Alirocumab dose was increased at Week 12 to 150 mg Q2W if Week 8 LDL-C was ≥1.8 mmol/L ( 70 mg/dL ) . Primary endpoint ( both studies ) was percentage change in calculated LDL-C from baseline to Week 24 . Mean LDL-C levels decreased from 3.7 mmol/L ( 144.7 mg/dL ) at baseline to 1.8 mmol/L ( 71.3 mg/dL ; −57.9 % vs. placebo ) at Week 24 in patients r and omized to alirocumab in FH I and from 3.5 mmol/L ( 134.6 mg/dL ) to 1.8 mmol/L ( 67.7 mg/dL ; −51.4 % vs. placebo ) in FH II ( P < 0.0001 ) . These reductions were maintained through Week 78 . LDL-C < 1.8 mmol/L ( regardless of cardiovascular risk ) was achieved at Week 24 by 59.8 and 68.2 % of alirocumab-treated patients in FH I and FH II , respectively . Adverse events result ed in discontinuation in 3.4 % of alirocumab-treated patients in FH I ( vs. 6.1 % placebo ) and 3.6 % ( vs. 1.2 % ) in FH II . Rate of injection site reactions in alirocumab-treated patients was 12.4 % in FH I and 11.4 % in FH II ( vs. 11.0 and 7.4 % with placebo ) . Conclusion In patients with HeFH and inadequate LDL-C control at baseline despite maximally tolerated statin ± other LLT , alirocumab treatment result ed in significant LDL-C lowering and greater achievement of LDL-C target levels and was well tolerated . Clinical trial registration Cinicaltrials.gov ( identifiers : NCT01623115 ; NCT01709500 ) CONTEXT Despite current st and ard of care , many patients at high risk of cardiovascular disease ( CVD ) still have elevated low-density lipoprotein cholesterol ( LDL-C ) levels . Alirocumab is a fully human monoclonal antibody inhibitor of proprotein convertase subtilisin/kexin type 9 . OBJECTIVE The objective of the study was to compare the LDL-C-lowering efficacy of adding alirocumab vs other common lipid-lowering strategies . DESIGN , PATIENTS , AND INTERVENTIONS Patients ( n = 355 ) with very high CVD risk and LDL-C levels of 70 mg/dL or greater or high CVD risk and LDL-C of 100 mg/dL or greater on baseline atorvastatin 20 or 40 mg were r and omized to one of the following : 1 ) add-on alirocumab 75 mg every 2 weeks ( Q2W ) sc ; 2 ) add-on ezetimibe 10 mg/d ; 3 ) double atorvastatin dose ; or 4 ) for atorvastatin 40 mg regimen only , switch to rosuvastatin 40 mg . For patients not achieving protocol -defined LDL-C goals , the alirocumab dose was increased ( blinded ) at week 12 to 150 mg Q2W . MAIN OUTCOME MEASURE The primary end point was percentage change in calculated LDL-C from baseline to 24 weeks ( intent to treat ) . RESULTS Among atorvastatin 20 and 40 mg regimens , respectively , add-on alirocumab reduced LDL-C levels by 44.1 % and 54.0 % ( P < .001 vs all comparators ) ; add-on ezetimibe , 20.5 % and 22.6 % ; doubling of atorvastatin dose , 5.0 % and 4.8 % ; and switching atorvastatin 40 mg to rosuvastatin 40 mg , 21.4 % . Most alirocumab-treated patients ( 87.2 % and 84.6 % ) achieved their LDL-C goals . Most alirocumab-treated patients ( 86 % ) maintained their 75-mg Q2W regimen . Treatment-emergent adverse events occurred in 65.4 % of alirocumab patients vs 64.4 % ezetimibe and 63.8 % double atorvastatin/switch to rosuvastatin ( data were pooled ) . CONCLUSIONS Adding alirocumab to atorvastatin provided significantly greater LDL-C reductions vs adding ezetimibe , doubling atorvastatin dose , or switching to rosuvastatin and enabled greater LDL-C goal achievement BACKGROUND Inhibition of proprotein convertase subtilisin/kexin type 9 serine protease ( PCSK9 ) result ed in large reductions of low-density lipoprotein cholesterol ( LDL-C ) in phase 1 trials . We assessed the efficacy and safety of various doses and dosing intervals of REGN727 , a monoclonal antibody to PCSK9 , added to statins , to further lower LDL-C in patients with heterozygous familial hypercholesterolaemia . METHODS This multicentre , r and omised , placebo-controlled phase 2 trial was done at 16 lipid clinics in the USA and Canada . Between Jan 18 , 2011 , and Nov 7 , 2011 , we enrolled adults with heterozygous familial hypercholesterolaemia and LDL-C concentrations of 2·6 mmol/L or higher on stable diet and statin dose , with or without ezetimibe . Patients were r and omly assigned to receive REGN727 150 mg , 200 mg , or 300 mg every 4 weeks , or 150 mg every 2 weeks , or placebo every 2 weeks ( ratio 1:1:1:1:1 ) . R and omisation was stratified by concomitant use of ezetimibe at baseline . Investigators , study staff , and patients were masked to treatment group . Blinding was maintained by administration of placebo alternating with REGN727 for the groups of 4 week dosing . The primary endpoint was mean percent reduction in LDL-C from baseline at week 12 and was analysed in the modified intention-to-treat population with an analysis of covariance ( ANCOVA ) model with treatment group . This trial is registered in Clinical Trials.gov , number NCT 01266876 . FINDINGS 77 patients were r and omly assigned to study groups ( 15 - 16 patients per group ) and all were analysed . Least-squares ( LS ) mean LDL-C reduction from baseline to week 12 was 28·9 % ( SE 5·08 ) for 150 mg every 4 weeks ( p=0·0113 ) , 31·54 % ( 4·91 ) for 200 mg every 4 weeks ( p=0·0035 ) , 42·53 % ( 5·09 ) for 300 mg every 4 weeks ( p<0·0001 ) , and 67·90 % ( 4·85 ) for 150 mg every 2 weeks ( p<0·0001 ) , compared with 10·65 % ( 5·04 ) with placebo . One serious adverse event was reported with placebo and none with REGN727 . No increases of more than three times the upper limit of normal were reported for hepatic transaminases or creatinine kinase . The most common adverse event was injection-site reaction with one patient in the group of 300 mg REGN727 terminating treatment . INTERPRETATION REGN727 was well tolerated and achieved substantial further LDL-C reduction in patients with heterozygous familial hypercholesterolaemia and elevated LDL-C treated with high-dose statins , with or without ezetimibe . REGN727 has the potential to provide optimum control of LDL-C in patients with this disorder . FUNDING Sanofi US and Regeneron Pharmaceuticals Incorporated BACKGROUND Alirocumab , a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 ( PCSK9 ) , has been shown to reduce low-density lipoprotein ( LDL ) cholesterol levels in patients who are receiving statin therapy . Larger and longer-term studies are needed to establish safety and efficacy . METHODS We conducted a r and omized trial involving 2341 patients at high risk for cardiovascular events who had LDL cholesterol levels of 70 mg per deciliter ( 1.8 mmol per liter ) or more and were receiving treatment with statins at the maximum tolerated dose ( the highest dose associated with an acceptable side-effect profile ) , with or without other lipid-lowering therapy . Patients were r and omly assigned in a 2:1 ratio to receive alirocumab ( 150 mg ) or placebo as a 1-ml subcutaneous injection every 2 weeks for 78 weeks . The primary efficacy end point was the percentage change in calculated LDL cholesterol level from baseline to week 24 . RESULTS At week 24 , the difference between the alirocumab and placebo groups in the mean percentage change from baseline in calculated LDL cholesterol level was -62 percentage points ( P<0.001 ) ; the treatment effect remained consistent over a period of 78 weeks . The alirocumab group , as compared with the placebo group , had higher rates of injection-site reactions ( 5.9 % vs. 4.2 % ) , myalgia ( 5.4 % vs. 2.9 % ) , neurocognitive events ( 1.2 % vs. 0.5 % ) , and ophthalmologic events ( 2.9 % vs. 1.9 % ) . In a post hoc analysis , the rate of major adverse cardiovascular events ( death from coronary heart disease , nonfatal myocardial infa rct ion , fatal or nonfatal ischemic stroke , or unstable angina requiring hospitalization ) was lower with alirocumab than with placebo ( 1.7 % vs. 3.3 % ; hazard ratio , 0.52 ; 95 % confidence interval , 0.31 to 0.90 ; nominal P=0.02 ) . CONCLUSIONS Over a period of 78 weeks , alirocumab , when added to statin therapy at the maximum tolerated dose , significantly reduced LDL cholesterol levels . In a post hoc analysis , there was evidence of a reduction in the rate of cardiovascular events with alirocumab . ( Funded by Sanofi and Regeneron Pharmaceuticals ; ODYSSEY LONG TERM Clinical Trials.gov number , NCT01507831 . ) Summary Background Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease , but also with modest hyperglycaemia , increased bodyweight , and modestly increased risk of type 2 diabetes , which in no way offsets their substantial benefits . We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely effects of PCSK9 inhibitors on diabetes risk . Methods In this mendelian r and omisation study , we used data from cohort studies , r and omised controlled trials , case control studies , and genetic consortia to estimate associations of PCSK9 genetic variants with LDL cholesterol , fasting blood glucose , HbA1c , fasting insulin , bodyweight , waist-to-hip ratio , BMI , and risk of type 2 diabetes , using a st and ardised analysis plan , meta-analyses , and weighted gene-centric scores . Findings Data were available for more than 550 000 individuals and 51 623 cases of type 2 diabetes . Combined analyses of four independent PCSK9 variants ( rs11583680 , rs11591147 , rs2479409 , and rs11206510 ) scaled to 1 mmol/L lower LDL cholesterol showed associations with increased fasting glucose ( 0·09 mmol/L , 95 % CI 0·02 to 0·15 ) , bodyweight ( 1·03 kg , 0·24 to 1·82 ) , waist-to-hip ratio ( 0·006 , 0·003 to 0·010 ) , and an odds ratio for type diabetes of 1·29 ( 1·11 to 1·50 ) . Based on the collected data , we did not identify associations with HbA1c ( 0·03 % , −0·01 to 0·08 ) , fasting insulin ( 0·00 % , −0·06 to 0·07 ) , and BMI ( 0·11 kg/m2 , −0·09 to 0·30 ) . Interpretation PCSK9 variants associated with lower LDL cholesterol were also associated with circulating higher fasting glucose concentration , bodyweight , and waist-to-hip ratio , and an increased risk of type 2 diabetes . In trials of PCSK9 inhibitor drugs , investigators should carefully assess these safety outcomes and quantify the risks and benefits of PCSK9 inhibitor treatment , as was previously done for statins . Funding British Heart Foundation , and University College London Hospitals NHS Foundation Trust ( UCLH ) National Institute for Health Research ( NIHR ) Biomedical Research Centre The effects of dyslipidemia on the risk of type 2 diabetes ( T2D ) and related traits are not clear . We used regression models and 140 lipid-associated genetic variants to estimate associations between circulating HDL cholesterol ( HDL-C ) , LDL cholesterol ( LDL-C ) , and triglycerides and T2D and related traits . Each genetic test was corrected for effects of variants on the other two lipid types and surrogates of adiposity . We used the largest data sets available : 34,840 T2D case and 114,981 control subjects from the DIAGRAM ( DIAbetes Genetics Replication And Meta- analysis ) consortium and up to 133,010 individuals without diabetes for insulin secretion and sensitivity from the MAGIC ( Meta-Analyses of Glucose and Insulin-related traits Consortium ) and GENESIS ( GENEticS of Insulin Sensitivity ) studies . Eight of 21 associations between groups of variants and diabetes traits were significant at the nominal level , including those between genetically determined lower HDL-C ( β = −0.12 , P = 0.03 ) and T2D and genetically determined lower LDL-C ( β = −0.21 , P = 5 × 10−6 ) and T2D . Although some of these may represent causal associations , we discuss why caution must be used when using Mendelian r and omization in the context of circulating lipid levels and diabetes traits . In conclusion , we found evidence of links between genetic variants associated with lipids and T2D , but deeper knowledge of the underlying genetic mechanisms of specific lipid variants is needed before drawing definite conclusions about causality based on Mendelian r and omization methodology BACKGROUND Evolocumab , a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 ( PCSK9 ) , significantly reduced low-density lipoprotein ( LDL ) cholesterol levels in short-term studies . We conducted two extension studies to obtain longer-term data . METHODS In two open-label , r and omized trials , we enrolled 4465 patients who had completed 1 of 12 phase 2 or 3 studies ( " parent trials " ) of evolocumab . Regardless of study -group assignments in the parent trials , eligible patients were r and omly assigned in a 2:1 ratio to receive either evolocumab ( 140 mg every 2 weeks or 420 mg monthly ) plus st and ard therapy or st and ard therapy alone . Patients were followed for a median of 11.1 months with assessment of lipid levels , safety , and ( as a prespecified exploratory analysis ) adjudicated cardiovascular events including death , myocardial infa rct ion , unstable angina , coronary revascularization , stroke , transient ischemic attack , and heart failure . Data from the two trials were combined . RESULTS As compared with st and ard therapy alone , evolocumab reduced the level of LDL cholesterol by 61 % , from a median of 120 mg per deciliter to 48 mg per deciliter ( P<0.001 ) . Most adverse events occurred with similar frequency in the two groups , although neurocognitive events were reported more frequently in the evolocumab group . The risk of adverse events , including neurocognitive events , did not vary significantly according to the achieved level of LDL cholesterol . The rate of cardiovascular events at 1 year was reduced from 2.18 % in the st and ard-therapy group to 0.95 % in the evolocumab group ( hazard ratio in the evolocumab group , 0.47 ; 95 % confidence interval , 0.28 to 0.78 ; P=0.003 ) . CONCLUSIONS During approximately 1 year of therapy , the use of evolocumab plus st and ard therapy , as compared with st and ard therapy alone , significantly reduced LDL cholesterol levels and reduced the incidence of cardiovascular events in a prespecified but exploratory analysis . ( Funded by Amgen ; OSLER-1 and OSLER-2 Clinical Trials.gov numbers , NCT01439880 and NCT01854918 . ) BACKGROUND Evolocumab , a monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) , significantly reduced low-density lipoprotein ( LDL ) cholesterol levels in phase 2 studies . We conducted a phase 3 trial to evaluate the safety and efficacy of 52 weeks of treatment with evolocumab . METHODS We stratified patients with hyperlipidemia according to the risk categories outlined by the Adult Treatment Panel III of the National Cholesterol Education Program . On the basis of this classification , patients were started on background lipid-lowering therapy with diet alone or diet plus atorvastatin at a dose of 10 mg daily , atorvastatin at a dose of 80 mg daily , or atorvastatin at a dose of 80 mg daily plus ezetimibe at a dose of 10 mg daily , for a run-in period of 4 to 12 weeks . Patients with an LDL cholesterol level of 75 mg per deciliter ( 1.9 mmol per liter ) or higher were then r and omly assigned in a 2:1 ratio to receive either evolocumab ( 420 mg ) or placebo every 4 weeks . The primary end point was the percent change from baseline in LDL cholesterol , as measured by means of ultracentrifugation , at week 52 . RESULTS Among the 901 patients included in the primary analysis , the overall least-squares mean ( ±SE ) reduction in LDL cholesterol from baseline in the evolocumab group , taking into account the change in the placebo group , was 57.0±2.1 % ( P<0.001 ) . The mean reduction was 55.7±4.2 % among patients who underwent background therapy with diet alone , 61.6±2.6 % among those who received 10 mg of atorvastatin , 56.8±5.3 % among those who received 80 mg of atorvastatin , and 48.5±5.2 % among those who received a combination of 80 mg of atorvastatin and 10 mg of ezetimibe ( P<0.001 for all comparisons ) . Evolocumab treatment also significantly reduced levels of apolipoprotein B , non-high-density lipoprotein cholesterol , lipoprotein(a ) , and triglycerides . The most common adverse events were nasopharyngitis , upper respiratory tract infection , influenza , and back pain . CONCLUSIONS At 52 weeks , evolocumab added to diet alone , to low-dose atorvastatin , or to high-dose atorvastatin with or without ezetimibe significantly reduced LDL cholesterol levels in patients with a range of cardiovascular risks . ( Funded by Amgen ; DESCARTES Clinical Trials.gov number , NCT01516879 . ) BACKGROUND Proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) increases serum LDL-cholesterol ( LDL-C ) concentrations . We assessed the effects of AMG 145 , a human monoclonal antibody against PCSK9 , in patients with hypercholesterolaemia in the absence of concurrent lipid-lowering treatment . METHODS In a phase 2 trial done at 52 centres in Europe , the USA , Canada , and Australia , patients ( aged 18 - 75 years ) with serum LDL-C concentrations of 2·6 mmol/L or greater but less than 4·9 mmol/L were r and omly assigned equally through an interactive voice response system to subcutaneous injections of AMG 145 70 mg , 105 mg , or 140 mg , or placebo every 2 weeks ; subcutaneous AMG 145 280 mg , 350 mg , or 420 mg or placebo every 4 weeks ; or oral ezetimibe 10 mg/day . The primary endpoint was percentage change from baseline in LDL-C concentration at week 12 . Analysis was by modified intention to treat . Study personnel and patients were masked to treatment assignment of AMG 145 or placebo . Ezetimibe assignment was open label . This trial is registered with Clinical Trials.gov , number NCT01375777 . FINDINGS 406 patients were assigned to AMG 145 70 mg ( n=45 ) , 105 mg ( n=46 ) , or 140 mg ( n=45 ) every 2 weeks ; AMG 145 280 mg ( n=45 ) , 350 mg ( n=45 ) , or 420 mg ( n=45 ) every 4 weeks ; placebo every 2 weeks ( n=45 ) or every 4 weeks ( n=45 ) ; or ezetimibe ( n=45 ) . AMG 145 significantly reduced LDL-C concentrations in all dose groups ( mean baseline LDL-C concentration 3·7 mmol/L [ SD 0·6 ] ; changes from baseline with every 2 weeks AMG 145 70 mg -41·0 % [ 95 % CI -46·2 to -35·8 ] ; 105 mg -43·9 % [ -49·0 to -38·7 ] ; 140 mg -50·9 % [ -56·2 to -45·7 ] ; every 4 weeks AMG 145 280 mg -39·0 % [ -44·1 to -34·0 ] ; 350 mg -43·2 % [ -48·3 to -38·1 ] ; 420 mg -48·0 % [ -53·1 to -42·9 ] ; placebo every 2 weeks -3·7 % [ -9·0 to 1·6 ] ; placebo every 4 weeks 4·5 % [ -0·7 to 9·8 ] ; and ezetimibe -14·7 % [ -18·6 to -10·8 ] ; p<0·0001 for all doses vs placebo or ezetimibe ) . Treatment-emergent adverse events occurred in 136 ( 50 % ) of 271 patients in the AMG 145 groups , 41 ( 46 % ) of 90 patients in the placebo groups , and 26 ( 58 % ) of 45 patients in the ezetimibe group ; no deaths or serious treatment-related adverse events were reported . INTERPRETATION The results of our study support the further assessment of AMG 145 in long-term studies with larger and more diverse population s including patients with documented statin intolerance . FUNDING Amgen OBJECTIVE To compare lipid-lowering efficacy of adding alirocumab to rosuvastatin versus other treatment strategies ( NCT01730053 ) . METHODS Patients receiving baseline rosuvastatin regimens ( 10 or 20 mg ) were r and omized to : add-on alirocumab 75 mg every-2-weeks ( Q2W ) ( 1-mL subcutaneous injection via pre-filled pen ) ; add-on ezetimibe 10 mg/day ; or double-dose rosuvastatin . Patients had cardiovascular disease ( CVD ) and low-density lipoprotein cholesterol ( LDL-C ) ≥70 mg/dL ( 1.8 mmol/L ) or CVD risk factors and LDL-C ≥100 mg/dL ( 2.6 mmol/L ) . In the alirocumab group , dose was blindly increased at Week 12 to 150 mg Q2W ( also 1-mL volume ) in patients not achieving their LDL-C target . Primary endpoint was percent change in calculated LDL-C from baseline to 24 weeks ( intent-to-treat ) . RESULTS 305 patients were r and omized . In the baseline rosuvastatin 10 mg group , significantly greater LDL-C reductions were observed with add-on alirocumab ( -50.6 % ) versus ezetimibe ( -14.4 % ; p < 0.0001 ) and double-dose rosuvastatin ( -16.3 % ; p < 0.0001 ) . In the baseline rosuvastatin 20 mg group , LDL-C reduction with add-on alirocumab was -36.3 % compared with -11.0 % with ezetimibe and -15.9 % with double-dose rosuvastatin ( p = 0.0136 and 0.0453 , respectively ; pre-specified threshold for significance p < 0.0125 ) . Overall , ∼80 % alirocumab patients were maintained on 75 mg Q2W . Of alirocumab-treated patients , 84.9 % and 66.7 % in the baseline rosuvastatin 10 and 20 mg groups , respectively , achieved risk-based LDL-C targets . Treatment-emergent adverse events occurred in 56.3 % of alirocumab patients versus 53.5 % ezetimibe and 67.3 % double-dose rosuvastatin ( pooled data ) . CONCLUSIONS The addition of alirocumab to rosuvastatin provided incremental LDL-C lowering versus adding ezetimibe or doubling the rosuvastatin dose Evolocumab ( AMG 145 ) , a fully human monoclonal antibody against PCSK9 , significantly reduced low-density lipoprotein cholesterol ( LDL-C ) levels in phase 2 and 3 studies . This phase 3 study evaluated the efficacy and safety of evolocumab plus atorvastatin in Japanese patients with hyperlipidemia or mixed dyslipidemia and high cardiovascular risk . Patients were r and omized to atorvastatin 5 or 20 mg/day for 4 weeks . Subsequently , patients underwent second r and omization to evolocumab 140 mg biweekly ( Q2W ) or 420 mg monthly ( QM ) or placebo Q2W or QM . Co primary end points were % change from baseline in LDL-C at week 12 and mean of weeks 10 and 12 . Secondary end points included change and % change in other lipids and proportion of patients reaching LDL-C < 70 mg/dl . Adverse events and laboratory values were recorded . Four hundred four patients were r and omized to study drug . At baseline , the mean ( SD ) age was 61 ( 10 ) years ( placebo ) and 62 ( 11 ) years ( evolocumab ) ; 39 % and 40 % were women ; 14 % and 12 % had cerebrovascular or peripheral arterial disease ; and 51 % and 47 % had diabetes . At entry , mean ( SD ) calculated LDL-C was 128 ( 23 ) mg/dL ; after stabilization on atorvastatin 5 and 20 mg/day , baseline LDL-C levels were 118 ( 35 ) and 94 ( 24 ) mg/dL , respectively . Mean LDL-C reductions at week 12 for evolocumab versus placebo ranged from 67 % to 76 % . No imbalances were observed in adverse events between treatment groups . Efficacy and safety for Q2W or QM evolocumab dosing were similar . In conclusion , in high-risk Japanese patients receiving stable statin therapy , evolocumab markedly reduced LDL-C and was well tolerated OBJECTIVES The primary objective of this study was to evaluate the low-density lipoprotein cholesterol (LDL-C)-lowering efficacy of 5 SAR236553/REGN727 ( SAR236553 ) dosing regimens versus placebo at week 12 in patients with LDL-C ≥100 mg/dl on stable atorvastatin therapy . Secondary objectives included evaluation of effects on other lipid parameters and the attainment of LDL-C treatment goals of < 100 mg/dl ( 2.59 mmol/l ) and < 70 mg/dl ( 1.81 mmol/l ) . BACKGROUND Serum proprotein convertase subtilisin kexin 9 ( PCSK9 ) binds to low-density lipoprotein receptors , increasing serum LDL-C. SAR236553 is a fully human monoclonal antibody to PCSK9 . METHODS This double-blind , parallel-group , placebo-controlled trial r and omized 183 patients with LDL-C ≥100 mg/dl ( 2.59 mmol/l ) on stable-dose atorvastatin 10 , 20 , or 40 mg for ≥6 weeks to : subcutaneous placebo every 2 weeks ( Q2W ) ; SAR236553 50 , 100 , or 150 mg Q2W ; or SAR236553 200 or 300 mg every 4 weeks ( Q4W ) , alternating with placebo for a total treatment period of 12 weeks . RESULTS SAR236553 demonstrated a clear dose-response relationship with respect to percentage LDL-C lowering for both Q2W and Q4W administration : 40 % , 64 % , and 72 % with 50 , 100 , and 150 mg Q2W , respectively , and 43 % and 48 % with 200 and 300 mg Q4W . LDL-C reduction with placebo at week 12 was 5 % . SAR236553 also substantially reduced non-high-density lipoprotein cholesterol , apolipoprotein B , and lipoprotein(a ) . SAR236553 was generally well tolerated . One patient on SAR236553 experienced a serious adverse event of leukocytoclastic vasculitis . CONCLUSIONS When added to atorvastatin , PCSK9 inhibition with SAR236553 further reduces LDL-C by 40 % to 72 % . These additional reductions are both dose- and dosing frequency-dependent . ( Efficacy and Safety Evaluation of SAR236553 [ REGN727 ] in Patients With Primary Hypercholesterolemia and LDL-cholesterol on Stable Atorvastatin Therapy ; NCT01288443 ) Importance Reducing levels of low-density lipoprotein cholesterol ( LDL-C ) with intensive statin therapy reduces progression of coronary atherosclerosis in proportion to achieved LDL-C levels . Proprotein convertase subtilisin kexin type 9 ( PCSK9 ) inhibitors produce incremental LDL-C lowering in statin-treated patients ; however , the effects of these drugs on coronary atherosclerosis have not been evaluated . Objective To determine the effects of PCSK9 inhibition with evolocumab on progression of coronary atherosclerosis in statin-treated patients . Design , Setting , and Participants The GLAGOV multicenter , double-blind , placebo-controlled , r and omized clinical trial ( enrollment May 3 , 2013 , to January 12 , 2015 ) conducted at 197 academic and community hospitals in North America , Europe , South America , Asia , Australia , and South Africa and enrolling 968 patients presenting for coronary angiography . Interventions Participants with angiographic coronary disease were r and omized to receive monthly evolocumab ( 420 mg ) ( n = 484 ) or placebo ( n = 484 ) via subcutaneous injection for 76 weeks , in addition to statins . Main Outcomes and Measures The primary efficacy measure was the nominal change in percent atheroma volume ( PAV ) from baseline to week 78 , measured by serial intravascular ultrasonography ( IVUS ) imaging . Secondary efficacy measures were nominal change in normalized total atheroma volume ( TAV ) and percentage of patients demonstrating plaque regression . Safety and tolerability were also evaluated . Results Among the 968 treated patients ( mean age , 59.8 years [ SD , 9.2 ] ; 269 [ 27.8 % ] women ; mean LDL-C level , 92.5 mg/dL [ SD , 27.2 ] ) , 846 had evaluable imaging at follow-up . Compared with placebo , the evolocumab group achieved lower mean , time-weighted LDL-C levels ( 93.0 vs 36.6 mg/dL ; difference , -56.5 mg/dL [ 95 % CI , -59.7 to -53.4 ] ; P < .001 ) . The primary efficacy parameter , PAV , increased 0.05 % with placebo and decreased 0.95 % with evolocumab ( difference , -1.0 % [ 95 % CI , -1.8 % to -0.64 % ] ; P < .001 ) . The secondary efficacy parameter , normalized TAV , decreased 0.9 mm3 with placebo and 5.8 mm3 with evolocumab ( difference , -4.9 mm3 [ 95 % CI , -7.3 to -2.5 ] ; P < .001 ) . Evolocumab induced plaque regression in a greater percentage of patients than placebo ( 64.3 % vs 47.3 % ; difference , 17.0 % [ 95 % CI , 10.4 % to 23.6 % ] ; P < .001 for PAV and 61.5 % vs 48.9 % ; difference , 12.5 % [ 95 % CI , 5.9 % to 19.2 % ] ; P < .001 for TAV ) . Conclusions and Relevance Among patients with angiographic coronary disease treated with statins , addition of evolocumab , compared with placebo , result ed in a greater decrease in PAV after 76 weeks of treatment . Further studies are needed to assess the effects of PCSK9 inhibition on clinical outcomes . Trial Registration clinical trials.gov Identifier : NCT01813422 BACKGROUND Serum proprotein convertase subtilisin/kexin 9 ( PCSK9 ) binds to low-density lipoprotein ( LDL ) receptors , increasing the degradation of LDL receptors and reducing the rate at which LDL cholesterol is removed from the circulation . REGN727/SAR236553 ( design ated here as SAR236553 ) , a fully human PCSK9 monoclonal antibody , increases the recycling of LDL receptors and reduces LDL cholesterol levels . METHODS We performed a phase 2 , multicenter , double-blind , placebo-controlled trial involving 92 patients who had LDL cholesterol levels of 100 mg per deciliter ( 2.6 mmol per liter ) or higher after treatment with 10 mg of atorvastatin for at least 7 weeks . Patients were r and omly assigned to receive 8 weeks of treatment with 80 mg of atorvastatin daily plus SAR236553 once every 2 weeks , 10 mg of atorvastatin daily plus SAR236553 once every 2 weeks , or 80 mg of atorvastatin daily plus placebo once every 2 weeks and were followed for an additional 8 weeks after treatment . RESULTS The least-squares mean ( ±SE ) percent reduction from baseline in LDL cholesterol was 73.2±3.5 with 80 mg of atorvastatin plus SAR236553 , as compared with 17.3±3.5 with 80 mg of atorvastatin plus placebo ( P<0.001 ) and 66.2±3.5 with 10 mg of atorvastatin plus SAR236553 . All the patients who received SAR236553 , as compared with 52 % of those who received 80 mg of atorvastatin plus placebo , attained an LDL cholesterol level of less than 100 mg per deciliter , and at least 90 % of the patients who received SAR236553 , as compared with 17 % who received 80 mg of atorvastatin plus placebo , attained LDL cholesterol levels of less than 70 mg per deciliter ( 1.8 mmol per liter ) . CONCLUSIONS In a r and omized trial involving patients with primary hypercholesterolemia , adding SAR236553 to either 10 mg of atorvastatin or 80 mg of atorvastatin result ed in a significantly greater reduction in LDL cholesterol than that attained with 80 mg of atorvastatin alone . ( Funded by Sanofi and Regeneron Pharmaceuticals ; Clinical Trials.gov number , NCT01288469 . ) BACKGROUND Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin – kexin type 9 ( PCSK9 ) and reduces levels of low‐density lipoprotein ( LDL ) cholesterol . We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk . METHODS In two parallel , multinational trials with different entry criteria for LDL cholesterol levels , we r and omly assigned the 27,438 patients in the combined trials to receive bococizumab ( at a dose of 150 mg ) subcutaneously every 2 weeks or placebo . The primary end point was nonfatal myocardial infa rct ion , nonfatal stroke , hospitalization for unstable angina requiring urgent revascularization , or cardiovascular death ; 93 % of the patients were receiving statin therapy at baseline . The trials were stopped early after the sponsor elected to discontinue the development of bococizumab owing in part to the development of high rates of antidrug antibodies , as seen in data from other studies in the program . The median follow‐up was 10 months . RESULTS At 14 weeks , patients in the combined trials had a mean change from baseline in LDL cholesterol levels of ‐56.0 % in the bococizumab group and + 2.9 % in the placebo group , for a between‐group difference of –59.0 percentage points ( P<0.001 ) and a median reduction from baseline of 64.2 % ( P<0.001 ) . In the lower‐risk , shorter‐ duration trial ( in which the patients had a baseline LDL cholesterol level of ≥70 mg per deciliter [ 1.8 mmol per liter ] and the median follow‐up was 7 months ) , major cardiovascular events occurred in 173 patients each in the bococizumab group and the placebo group ( hazard ratio , 0.99 ; 95 % confidence interval [ CI ] , 0.80 to 1.22 ; P=0.94 ) . In the higher‐risk , longer‐ duration trial ( in which the patients had a baseline LDL cholesterol level of ≥100 mg per deciliter [ 2.6 mmol per liter ] and the median follow‐up was 12 months ) , major cardiovascular events occurred in 179 and 224 patients , respectively ( hazard ratio , 0.79 ; 95 % CI , 0.65 to 0.97 ; P=0.02 ) . The hazard ratio for the primary end point in the combined trials was 0.88 ( 95 % CI , 0.76 to 1.02 ; P=0.08 ) . Injection‐site reactions were more common in the bococizumab group than in the placebo group ( 10.4 % vs. 1.3 % , P<0.001 ) . CONCLUSIONS In two r and omized trials comparing the PCSK9 inhibitor bococizumab with placebo , bococizumab had no benefit with respect to major adverse cardiovascular events in the trial involving lower‐risk patients but did have a significant benefit in the trial involving higher‐risk patients . ( Funded by Pfizer ; SPIRE‐1 and SPIRE‐2 Clinical Trials.gov numbers , NCT01975376 and NCT01975389 . Abstract Aim . To evaluate the relation of proprotein convertase subtilisin-kexin type 9 ( PCSK9 ) levels to coronary artery disease ( CAD ) . Methods . A total of 1031 consecutive individuals ( 552 CAD and 479 controls ) were prospect ively enrolled . The associations of plasma PCSK9 levels with the incidence and severity of CAD were investigated . Further , mediator analysis was performed to detect the potential mechanisms of the associations . Results . No difference in PCSK9 levels between CAD patients and controls was detected ( median 224.75 versus 224.64 ng/mL , P > 0.05 ) . However , the CAD group had higher PCSK9 levels than the control group when adjusting for the confounding factors ( 228.03 ± 1.01 versus 219.28 ± 1.02 ng/mL , P = 0.019 ) . PCSK9 levels were also associated with the severity of CAD assessed by the Gensini score ( GS ) system ( P for trend < 0.05 ) . Logistic regression analysis showed that PCSK9 levels were associated with an increased CAD risk ( OR 3.296 and 5.130 for the incidence and severity , respectively ) . Importantly , mediator analysis indicated that the effects of PCSK9 levels on CAD were mediated by lipid ( around 20 % ) and inflammation ( around 15 % ) . Conclusions . PCSK9 levels were positively associated with the severity of CAD ; the relatively important mechanisms including lipid and inflammation pathways were partly involved in this association Background — Despite statin treatment , many patients with heterozygous familial hypercholesterolemia do not reach desired low-density lipoprotein cholesterol ( LDL-C ) targets . AMG 145 , a fully human monoclonal antibody against proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) serine protease , demonstrated significant reductions in LDL-C in phase 1 studies . This phase 2 , multicenter , double-blind , r and omized , placebo-controlled , dose-ranging study evaluated the efficacy and safety of AMG 145 in heterozygous familial hypercholesterolemia patients . Methods and Results — Patients with heterozygous familial hypercholesterolemia diagnosed by Simon Broome criteria with LDL-C ≥2.6 mmol/L ( 100 mg/dL ) despite statin therapy with or without ezetimibe were r and omized 1:1:1 to AMG 145 350 mg , AMG 145 420 mg , or placebo-administered subcutaneously every 4 weeks . The primary end point was percentage change from baseline in LDL-C at week 12 . Of 168 patients r and omized , 167 received investigational product and were included in the full analysis set ( mean [ SD ] age , 50 [ 13 ] years ; 47 % female ; 89 % white ; mean [ SD ] baseline LDL-C , 4.0 [ 1.1 ] mmol/L ( 156 [ 42 ] mg/dL ) ) . At week 12 , LDL-C reduction measured by preparative ultracentrifugation ( least squares mean [ st and ard error ( SE ) ] ) was 43 (3)% and 55 (3)% with AMG 145 350 mg and 420 mg , respectively , compared with 1 (3)% increase with placebo ( P<0.001 for both dose groups ) . Serious adverse events ( not considered treatment-related ) occurred in 2 patients on AMG 145 . Conclusions — AMG 145 administered every 4 weeks yielded rapid and substantial reductions in LDL-C in heterozygous familial hypercholesterolemia patients despite intensive statin use , with or without ezetimibe , with minimal adverse events and good tolerability . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01375751 |
1,297 | 11,253,970 | INTERPRETATION There is much inconsistency regarding emotional and cognitive care , although one relatively consistent finding is that physicians who adopt a warm , friendly , and reassuring manner are more effective than those who keep consultations formal and do not offer reassurance | BACKGROUND Throughout history , doctor-patient relationships have been acknowledged as having an important therapeutic effect , irrespective of any prescribed drug or treatment .
We did a systematic review to determine whether there was any empirical evidence to support this theory . | A group of 200 patients who presented in general practice with symptoms but no abnormal physical signs and in whom no definite diagnosis was made were r and omly selected for one of four consultations : a consultation conducted in a " positive manner , " with and without treatment , and a consultation conducted in a " non-positive manner , " called a negative consultation , with and without treatment . Two weeks after consultation there was a significant difference in patient satisfaction between the positive and negative groups but not between the treated and untreated groups . Similarly , 64 % of those receiving a positive consultation got better , compared with 39 % of those who received a negative consultation ( p = 0.001 ) and 53 % of those treated got better compared with 50 % of those not treated ( p = 0.5 ) This study looked at the possible harmful effects of detection and treatment for hypertension . Patients with borderline blood pressure ( diastolic 96 - 109 mmHg ) were r and omized into two groups : an intervention group receiving treatment for hypertension and a control group not told about any problem and left untreated . The morbidity in these two groups were studied for differences . During the period studied , the patients in the investigation group saw the doctor more frequently and had a larger number of diseases classified than the control group . When consultations involving hypertension and its follow up were excluded , however , no differences were demonstrable between the groups . Problem behaviour , psychosomatic and functional affections and symptom diagnoses were evenly distributed over the two groups . The difference in blood pressure between the two groups after completion of the study was not marked : the decrease in diastolic blood pressure averaged 7.6 mmHg in the control group versus 9.1 mmHg in the intervention group . In cases where the initial blood pressure values are only slightly raised , careful monitoring of blood pressure over a long period seems to be as effective as treatment for hypertension . The general practitioner should focus especially on anticipation in this sense BACKGROUND When initiating treatment , it has been shown that only one quarter of the physicians discuss potential side effects with patients . There are several possible reasons , but , in particular , many physicians are concerned that the power of suggestion may lead some patients to experience an increase in side effects if they are fully informed . Accordingly , this study was design ed to determine whether providing patients with information about potential side effects of new medications increases the reported incidence of those side effects . METHODS All clinic patients are r and omly assigned to one of four firms . Two firms served as the intervention group and two served as control groups . All patients receiving new prescriptions for the angiotensin-converting enzyme inhibitors , trimethoprim/sulfamethoxazole , or nonsteroidal anti-inflammatory drugs were recruited . Patients without telephones were excluded . Intervention patients received verbal instructions and a h and out describing the name , purpose , dose , and three most common side effects of the drug . Control patients received usual discharge instructions . Patients were interviewed 14 to 21 days later using a st and ardized question naire . RESULTS There was no difference in incidence of targeted side effects for specific medications between the study groups ( 38 % vs 37 % ) . Study groups were similar with regard to age , sex , financial status , and type of medication prescribed . CONCLUSION Informing patients of potential side effects prior to starting a new medication does not lead to an increased incidence of those side effects . This should not be a reason for physicians to avoid warning patients of potential side effects To examine whether written informed consent might influence the results of clinical trials the effect of placebo when given with or without informed consent to patients suffering from insomnia was studied . The study was a single blind observer blinded trial , and patients were paired according to sex , age , and hospital environment . R and omisation assigned the first patient of each pair to the control group ( without informed consent ) or the group to give informed consent . Of the 56 patients , 26 refused to give informed consent , and the age and sex distribution of these differed significantly ( p less than 0.02 ) from the 30 pairs of patients ultimately enrolled into the study . In this " biased " sample , the hypnotic activity of placebo was significantly higher in the control group ( p less than 0.05 ) . It is concluded that the informed consent procedure biases the results of clinical trials and might affect their general applicability We carried out two studies to determine the effects of feedback on subsequent blood pressure and heart rate readings in subjects without significant cardiovascular abnormalities . In both studies the subjects were r and omly assigned to be told that their blood pressure was normal or was high or to receive no feedback at all ; 3 minutes later another reading was taken and correct feedback provided . Study 1 was done in 114 patients who attended a family practice teaching unit for an office visit ; subjects taking cardioactive medication or with chronically elevated blood pressure ( diastolic pressure more than 95 mm Hg ) or known low pressure ( diastolic pressure less than 60 mm Hg ) were excluded . Half of the subjects received feedback from a nurse and the other half from a physician . We found no effect of type of feedback or type of practitioner on subsequent readings . No adaptation of diastolic blood pressure or heart rate took place , whereas a similar rest period in the laboratory consistently triggers cardiovascular adaptation . Given the field nature of the study it was not clear whether the intervention was not powerful or whether the practitioner-patient interactions diffused the effects of an otherwise powerful intervention . Therefore , a second study with the same design was carried out in a controlled laboratory setting with 61 university students who believed they were in the adaptation phase of an experimental stress protocol . The subjects did not interact with the experimenter , who provided only the initial feedback , via intercom . The findings replicated those of study 1 : type of feedback had no significant effect on subsequent blood pressure levels , and all types of feedback prevented cardiovascular adaptation . We recommend that patients be allowed to rest alone for at least 10 minutes before blood pressure is measured . Our findings suggest that practitioners need not be concerned about telling normotensive or borderline hypertensive patients that their blood pressure is elevated OBJECTIVE To ascertain whether the quality of physician-patient communication makes a significant difference to patient health outcomes . DATA SOURCES The MEDLINE data base was search ed for articles published from 1983 to 1993 using " physician-patient relations " as the primary medical subject heading . Several bibliographies and conference proceedings were also review ed . STUDY SELECTION R and omized controlled trials ( RCTs ) and analytic studies of physician-patient communication in which patient health was an outcome variable . DATA EXTRACTION The following information was recorded about each study : sample size , patient characteristics , clinical setting , elements of communication assessed , patient outcomes measured , and direction and significance of any association found between aspects of communication and patient outcomes . DATA SYNTHESIS Of the 21 studies that met the final criteria for review , 16 reported positive results , 4 reported negative ( i.e. , nonsignificant ) results , and 1 was inconclusive . The quality of communication both in the history-taking segment of the visit and during discussion of the management plan was found to influence patient health outcomes . The outcomes affected were , in descending order of frequency , emotional health , symptom resolution , function , physiologic measures ( i.e. , blood pressure and blood sugar level ) and pain control . CONCLUSIONS Most of the studies review ed demonstrated a correlation between effective physician-patient communication and improved patient health outcomes . The components of effective communication identified by these studies can be used as the basis both for curriculum development in medical education and for patient education programs . Future research should focus on evaluating such educational programs To determine whether informed consent in a therapeutic trial modifies the analgesic effect of naproxen and placebo , we conducted a prospect i ve , r and omised , single dose , placebo-controlled trial . Patients were r and omly selected to receive or not information concerning the study . All patients included were then given a single dose of naproxen and placebo according to a crossover , double-blind design . Forty-nine patients with mild or moderate cancer pain which did not need narcotic analgesics entered the study . Twenty-five received both treatments without any information and constituted the uninformed group . Twenty-four had a complete information about the trial ; six refused to participate . The 18 others constituted the informed-consent group . Visual analogue scales of pain before and 30 , 60 , 120 and 180 min after the intake of naproxen and placebo were recorded . As an analgesic , naproxen was more effective than placebo in both groups of patients ( p = 0.001 ) . For naproxen as well as for placebo , the analgesic effect was better in the informed-consent group compared to the uninformed group ( p = 0.012 ) . The difference in therapeutic activity between naproxen and placebo was moderately higher in the uninformed patients ( p = 0.08 ) . We concluded that , in contrast with parallel studies , giving information in a crossover , placebo-controlled trial may increase the apparent efficacy of both the tested agent and the placebo , and decrease the perceived difference the two The influence of four variables ( status of communicator of drug effects , attitude of dentist , attitude of dental technician , and message of drug effects ) on the obtainment of placebo effects in an oral surgery clinic was investigated . Dependent variables were ( 1 ) rating of pain experienced from m and ibular-block injection , ( 2 ) pre-post placebo state anxiety , and ( 3 ) pre-postplacebo fear of injection . Enthusiastic messages of drug effects produced statistically and clinical ly significant reductions in postplacebo fear of injection and state anxiety and markedly lower ratings of pain experienced during injection of local anesthetic . Although there was a strong tendency for positive placebo effects to occur when the dental staff was perceived as friendly and supportive , only the attitude factors obtained statistical significance . The status of the communicator accounted for very small portions of the variance Homeless adults often visit emergency departments and often leave dissatisfied . We tested whether compassionate care , by improving patient satisfaction , can alter subsequent use of emergency services . We identified 133 consecutive homeless adults visiting one inner-city emergency department who were not acutely psychotic , extremely intoxicated , unable to speak English , or medically unstable . Half were r and omly assigned to receive compassionate contact from trained volunteers . All patients otherwise had usual care and were followed for repeat visits to emergency departments . We found that rates of use were high , with patients making an average of seven visits a year ( 0.60 per month ) . More than a third of all patients made two or more visits within two days of each other . The average number of visits per month after intervention was significantly lower for patients who received compassionate care ( 0.43 vs 0.65 , p = 0.018 ) . Analyses adjusting for each patient 's previous rate of use confirmed that compassionate care led to a one third reduction in the number of return visits within one month ( 95 % CI 14 to 40 % ) . Compassionate management of selected homeless adults decreases repeat visits to the emergency department . One explanation is that patients tend to return frequently until they are satisfied with their treatment Edrophonium is a widely used provocative agent in the evaluation of noncardiac chest pain , with reported positivity rates of 30 - 55 % . The influence of a subjective response and psychological factors on test results have not been examined previously . A retrospective analysis was performed to compare positivity rates for three physicians in the same laboratory . This was followed by a prospect i ve study of 62 patients with noncardiac chest pain r and omized to two groups . Group 1 patients were told that intravenous medication was given to observe changes in the tracing . Group 2 patients were told that the injection was to elicit their usual pain . During the 2-yr retrospective review , 260 patients were tested . The positivity rate varied from 31.1 % with physician A to 20.2 % with physician B and 7.5 % for physician C ( p = 0.001 for A vs. C , and p = 0.04 for B vs. C ) . In the prospect i ve study , chest pain was elicited in nine of 62 patients ( 14.5 % ) . Two of the 29 patients in group 1 ( 6.9 % ) and seven of 33 patients in group 2 ( 21.2 % ) contributed to this result . Contraction amplitude and duration increased similarly in all groups . These data suggest that edrophonium testing may be influenced by coaching , that manometric changes are similar in positive and negative tests , and that the prevalence of positive tests is lower than previously reported This study evaluated the effects of placebo medication on pulmonary responses in asthmatics , and investigated the roles of expectancy and anxiety . Twelve adult asthmatics were recruited for a laboratory experiment described as a study of the effectiveness of a new bronchodilator . Distilled nebulized water was inhaled in each session . The solution was described as water in session 1 ( control ) , while in sessions 2 and 3 subjects were told that the nebulizer contained a chemical likely to cause chest tightness and wheezing ( bronchoconstrictive suggestion ) . Prior to the inhalation sequence in sessions 2 and 3 , subjects inhaled from an aerosol that they were told contained either a powerful new drug ( placebo ) or a non-active substance ( neutral ) . Pulmonary function was measured with the forced oscillation technique and spirometry , while autonomic parameters , anxiety and expectancies were also monitored . Pulmonary function deteriorated following the inhalations accompanied by bronchoconstrictive suggestion , and this effect was abolished by pre-treatment with placebo . Neither subject expectations nor changes in anxiety were associated with the experimental manipulations . The implication s of these results for theories of placebo action are considered The effects of an anorexigenic agent ( dextroamphetamine ) and a placebo on weight loss in 64 obese female patients were evaluated over a period of 4 weeks . Half of the patients were field dependent and half were field independent . This psychological categorization of the patients refers to individual differences in analytic functioning in perception that can be objective ly evaluated and appears to parallel personality trait differences that have been noted between placebo reactors and nonreactors . An investigational drug or known drug treatment condition was created . Data from the study showed that : ( 1 ) Patients on dextroamphetamine lost more weight than patients on placebo . ( 2 ) Patients who were treated under known drug conditions lost more weight during the first week but not during the full 4 weeks . ( 3 ) Field‐dependent patients under known drug conditions did not lose any more weight than field‐independent patients under the same conditions . ( 4 ) There was considerable variation in the weight loss achieved by the patients of the same physician Aim : To determine whether orally delivered instructions can modify the intensity and direction of blood pressure and heart rate fluctuation . Methods : The blood pressure of 120 subjects , 60 hypertensive and 60 normotensive , was measured before and after oral instructions . The normotensive subjects were selected from a sample of university students and the hypertensive patients were selected at a routine medical screening . Each sample of 60 subjects was r and omly divided into four groups of 15 . Each subject was left seated alone in a room for 5min . The research er then measured the subjects ' blood pressure and heart rate . Following this , each group of normotensives and hypertensives was told that their blood pressure would diminish , or that it would not change or that it would increase . The control group was given no instructions . After 5 min the blood pressure and heart were measured again . Results : In the normotensive and hypertensive groups who were told that their blood pressure would increase , systolic blood pressure increased by 4.3 and 2.5mmHg , respectively . In the groups who were told that their blood pressure would decrease , systolic pressure fell by 7.8 and 7.4 mmHg , respectively . Those who were told that no change would occur showed a systolic pressure decrease of 3.5 and 1.8 mmHg , respectively . In the control groups systolic blood pressure decreased by 5.6 and 4.2 mmHg , respectively . Conclusions : These results show that oral instructions are a source of variation in the assessment of blood pressure and emphasize the need for 24-h blood pressure monitoring to eliminate this type of variation Topical anesthetics are routinely used to reduce the discomfort that patients perceive during dental injections . The purpose of this investigation was to correlate the expectancy of pain and the effect of pretreatment instructions with the severity of pain perceived upon topical anesthetic use and dental injection . The treatment , topical placebo versus topical anesthetic , was administered in a double-blind manner . Following testing for expectations , the administration of instructions , and placement of the topical , the injection was given . The patients were then asked to rate their injection experience on a posttreatment question naire . The results of this investigation reinforce the importance of psychological variables in the mediation of pain perceived during dental procedures SIR,-I hope that many have read and approved the article by Drs . F. N. Bamford and J. A. Davis ( Supplement , 20 January , p. 20 ) . The need for a modified , exp and ed , and integrated service to meet the changed pattern of child health and to provide an effective medical contribution to those who at present receive only token attention , or even none at all , has been recognized by some of us for several years . If professional attitudes had been more favourable , comprehensive child health services would have evolved before now . The current spate of reorganization stimulates hope that the time is ripe for such integration . Administrative changes alone , however , will not be sufficient . Attitudes must change . In particular there must be wider appreciation of the value of the promotion of optimum health and development for all children , recognition of the value of developmental stimulation and guidance , and acknowledgement that the paediatrician grappling with the multifaceted problem of a disabled child in the community requires skills just as complex and dem and ing as those required of a hospital-based paediatrician focusing upon a problem in depth . Many things can and should be done . The more important are as follows : ( a ) Increase undergraduate teaching of child health and development . The introduction of child development and behavioural sciences into the pre clinical years is praiseworthy , but must be matched by practical demonstrations of developmental paediatrics in the clinical years . ( b ) Accept that the promotion of child health is a basic part of medical practice and not just another item to be added on a fee-for-service basis . ( c ) Plan and make available vocational training programmes for the many paediatricians required by the community child health services . ( d ) Create a journal of child health and development as a focal point of the multidisciplinary activities in this field . Tt is truly amazing that no journal which really meets the requirements exists in this country . Obviously some of these are long-tenni aims , but there are many items on which we can begin this very day if we so wish . If we want our children to have the best prospect s for health and development , we must work for these changes ourselves . We can not sit back and hope that they will suddenly appear as if by an administrative sleight of h and .-I am , etc . OBJECTIVE To examine the effects of using positive or negative frames to describe influenza vaccine benefits and side effects on patients ' expectations , decisions , decisional conflict , and reported side effects . METHODS 292 previously unimmunized patients with chronic respiratory or cardiac disease were r and omly assigned to receive benefit/risk information that was framed : ( 1 ) positively as the percentage who remain free of influenza and have no vaccine side effects , or ( 2 ) negatively as the percentage who acquire influenza and have vaccine side effects . Question naires elicited expectations , decisions , and decisional conflict . Vaccines were telephoned 3 days later for a self-report of local and systemic side effects and work absenteeism . RESULTS Both groups had similar immunization rates and decisional conflict scores . The positive frame group had lower and more realistic expectations of vaccine side effects , fewer systemic side effects , and less work absenteeism ( p < 0.05 ) . CONCLUSION In contrast to previous studies of health care workers , framing did not influence patients ' decisions , possibly due to the patients ' awareness of their higher risk of influenza complications and greater desire to follow recommendations . The common practice of using negative frames when describing probabilities of side effects may need to be reexamined , considering its deleterious influence on self-reported side effects and work absenteeism frequent development of tachyphylaxis apart from numerous other toxic reactions and the painfulness of the injections . The main advantage of dimercaprol is that the molecule is not charged , is soluble in lipids , and is able to cross the blood-brain barrier fairly easily compared with penicillamine , trientine dihydrochloride , and unithiol , which are highly charged . Treatment with unithiol was started in two other patients . The first developed a fever of 39"C four hours after the test dose and a 50 ° , fall in the leucocyte count . A further challenge dose caused a similar reaction and treatment was not pursued . This patient was subsequently managed with tetrathiomolyb date .3 The second patient took unithiol for 10 days before refusing it because of intense nausea and a change in taste . Other patients have received single test doses , and the result ing cupruresis has been comparable with that after penicillamine and trientine dihydrochloride in most cases . Unithiol may well prove to be yet one more fall back treatment for patients who develop intolerance to penicillamine At 45 general- practice surgery sessions 200 patients in whom no definite diagnosis could be made were r and omly selected for one of two procedures . Either they were given a symptomatic diagnosis and medications , or they were told that they had no evidence of disease and therefore they required no treatment . No difference in outcome was found between these two methods as judged by the return or not of the patient within one month and his statement that he did or did not get better |
1,298 | 26,272,326 | Conclusions There was no evidence that school-based smoking prevention programs have a significant effect on preventing adolescent girls from smoking . | Background The purpose of this review is to study the effect of school-based interventions on smoking prevention for girls . | 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 BACKGROUND AND OBJECTIVE To develop a checklist of items measuring the quality of reports of r and omized clinical trials ( RCTs ) assessing nonpharmacological treatments ( NPTs ) . STUDY DESIGN AND SETTING The Delphi consensus method was used to select and reduce the number of items in the checklist . A total of 154 individuals were invited to participate : epidemiologists and statisticians involved in the field of methodology of RCTs ( n = 55 ) , members of the Cochrane Collaboration ( n = 41 ) , and clinicians involved in planning NPT clinical trials ( n = 58 ) . Participants ranked on a 10-point Likert scale whether an item should be included in the checklist . RESULTS Fifty-five experts ( 36 % ) participated in the survey . They were experienced in systematic review s ( 68 % were involved in the Cochrane Collaboration ) and in planning RCTs ( 76 % ) . Three rounds of the Delphi method were conducted to achieve consensus . The final checklist contains 10 items and 5 subitems , with items related to the st and ardization of the intervention , care provider influence , and additional measures to minimize the potential bias from lack of blinding of participants , care providers , and outcome assessors . CONCLUSIONS This tool can be used to critically appraise the medical literature , design NPT studies , and assess the quality of trial reports included in systematic review OBJECTIVES : Media Detective is a 10-lesson elementary school substance use prevention program developed on the basis of the message interpretation processing model design ed to increase children 's critical thinking skills about media messages and reduce intent to use tobacco and alcohol products . The purpose of this study was to conduct a short-term , r and omized , controlled trial to evaluate the effectiveness of Media Detective for achieving these goals . METHODS : Elementary schools were r and omly assigned to conditions to either receive the Media Detective program ( n = 344 ) or serve in a waiting list control group ( n = 335 ) . RESULTS : Boys in the Media Detective group reported significantly less interest in alcohol-br and ed merch and ise than boys in the control group . Also , students who were in the Media Detective group and had used alcohol or tobacco in the past reported significantly less intention to use and more self-efficacy to refuse substances than students who were in the control group and had previously used alcohol or tobacco . CONCLUSIONS : This evaluation provides evidence that Media Detective can be effective for substance use prevention in elementary school – aged children . Notably , media-related cognitions about alcohol and tobacco products are malleable and relevant to the development and maintenance of substance use behaviors during late childhood . The findings from this study suggest that media literacy – based interventions may serve as both a universal and a targeted prevention program that has potential for assisting elementary school children in making healthier , more informed decisions about use of alcohol and tobacco products The Life Education organization offers a drug education programme to an estimated one million Australian primary schoolchildren . It is believed the programme delays experimentation with or initiation into smoking , alcohol use and the taking of analgesics . This study examined the short-term public health effects on 3000 11- and 12-year-old students , of whom 1700 were exposed to 5 consecutive years of the programme . The other 1300 students were not exposed to the programme . After controlling for the known predictors of social drug use there was no evidence that Life Education students , when compared with students receiving conventional school-based drug education , were less likely to have smoked , were less likely to have drunk or were less likely to have used analgesics . Indeed , the evidence suggested that Life Education-students were slightly more likely to use these substances , and that the programme had different effects on boys ' and girls ' drug use . Given that these findings are consistent with previous research evaluating similar drug education programmes , it is hypothesized they are most likely to do with the design of the programme itself 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 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 Media Ready Program was design ed as a middle school , media literacy education , preventive intervention program to improve adolescents ' media literacy skills and reduce their intention to use alcohol or tobacco products . In a short-term efficacy trial , schools in North Carolina were r and omly assigned to conditions ( Media Ready : n = 214 ; control : n = 198 ) . Boys in the Media Ready group reported significantly less intention to use alcohol in the future than did boys in the control group . Also , students in the Media Ready group who had used tobacco in the past reported significantly less intention to use tobacco in the future than did students in the control group who had previously used tobacco . Multilevel multiple mediation analyses suggest that the set of logical analysis Message Interpretation Processing variables mediated the program 's effect on students ' intentions to use alcohol or tobacco in the future 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 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 Background : Studies of effectiveness of school-based prevention of substance misuse have generally overlooked gender differences . The purpose of this work was to analyse gender differences in the effectiveness of a new European school-based curriculum for prevention of substance misuse among adolescents . Methods : The European Drug Abuse Prevention ( EU-Dap ) trial took place in seven European countries during the school year 2004–05 . Schools were r and omly assigned to either a control group or a 12-session st and ardised curriculum ( “ Unplugged ” ) based on a comprehensive social influence model . The analytical sample consisted of 6359 students ( 3324 boys and 3035 girls ) . The use of cigarettes , alcohol and illicit drugs , adolescents ’ knowledge and opinions about substances , as well as social and personal skills were investigated through a self-completed anonymous question naire administered at enrolment and 3 months after the end of the programme . Adjusted Prevalence Odds Ratios were calculated as the measure of association between the intervention and behavioural outcomes using multilevel regression modelling . Results : At enrolment , boys were more likely than girls to have used cannabis and illicit drugs , whereas girls had a higher prevalence of cigarette smoking . At the follow-up survey , a significant association between the programme and a lower prevalence of all behavioural outcomes was found among boys , but not among girls . Age and self-esteem emerged as possible modifiers of these gender differences , but effects were not statistically significant . Conclusions : Comprehensive social influence school curricula against substance misuse in adolescence may perform differently among girls and boys , owing to developmental and personality factors INTRODUCTION A smoking prevention program was developed to prepare children in elementary school for secondary school . This study assessed the effects on smoking in secondary school . METHODS In 2002 , 121 schools in The Netherl and s were r and omly assigned to the intervention or control group . The intervention group received 3 lessons in 5th grade of elementary school and a second 3 lessons in 6th grade . The control group received " usual care " . Students completed 5 question naires : before and after the lessons in 5th and 6th grade and in the first class of secondary school . At baseline , 3173 students completed the question naire ; 57 % completed all question naires . RESULTS The program had limited effect at the end of elementary school . One year later in secondary school significant effects on behavioral determinants and smoking were found . The intervention group had a higher intention not to smoke ( β=0.13 , 95 % confidence interval=0.01 - 0.24 ) and started to smoke less often than the control group ( odds ratio=0.59 , 95 % confidence interval=0.35 - 0.99 ) : smoking increased from 2.5 % to 3.6 % in the intervention group and from 3.2 % to 6.5 % in the control group . Girls showed the largest differences in smoking between intervention and control condition . CONCLUSIONS A prevention program in elementary school seems to be effective in preventing smoking This article presents the short-term effects of a pilot study of keepin’it REAL ( Manténte REAL ) conducted in central Mexico by a binational team of investigators . This middle school-based model program for preventing substance use was adapted for Mexico linguistically but not culturally . Two Guadalajara public middle schools were recruited and r and omly assigned to either implement the prevention program or serve as a control site . The program was implemented in the treatment site by the students ’ regular teachers , who were trained by the research team . Seventh grade rs in ten classrooms in the treatment and control schools ( N = 432 ) completed a pretest and posttest survey in Spanish similar to the survey utilized in the original efficacy trial of keepin’it REAL in the US . T-tests and OLS regressions were conducted to determine the effects of the intervention on substance use outcomes . Differences between treatment and control groups in frequency of use of alcohol and tobacco , the two substances of choice in this sample , were significant and in the desired direction . Differences in amount of use were also in the preferred direction but were not significant for alcohol and only marginally significant for tobacco . When the sample was split by gender , statistically significant treatment effects remained for females but were not observed among males . Effects of the linguistically adapted version of keepin’it REAL appears to be driven by the change in female use ; however , the difference in male and female outcomes was not statistically significant . Implication s for cultural adaptation and prevention in Mexico are discussed from a communication competency perspective . The promising results of the pilot study suggest that the linguistic adaptation was effective , but that a comprehensive cultural adaptation of keepin’it REAL in partnership with Mexican investigators and communities may be warranted OBJECTIVES We assessed the effectiveness of a 2-year multicomponent , school-based intervention design ed to reduce tobacco use rates among adolescents in an urban area of India . METHODS Students from 32 schools in Delhi and Chennai , India , were recruited and r and omly assigned to an intervention or control group . Baseline , intermediate , and outcome data were collected from 2 cohorts of 6th- and 8th- grade students in 2004 ; 14,063 students took part in the study and completed a survey in 2004 , 2005 , or 2006 . The intervention consisted of behavioral classroom curricula , school posters , a parental involvement component , and peer-led activism . The main outcome measures were self-reported use of cigarettes , bidis ( small h and -rolled , often flavored , cigarettes ) , and chewing tobacco and future intentions to smoke or use chewing tobacco . RESULTS Findings showed that students in the intervention group were significantly less likely than were students in the control group to exhibit increases in cigarette smoking or bidi smoking over the 2-year study period . They were also less likely to intend to smoke or chew tobacco in the future . CONCLUSIONS School-based programs similar to the intervention examined here should be considered as part of a multi strategy approach to reducing tobacco use among young people in India The issue of prevention of tobacco use has received a great deal of attention in recent years . As an outgrowth of this interest , several smoking prevention programs based on a social influence approach have been developed . One example of these types of programs is the Peer Assisted Learning ( PAL ) prevention program which was produced by Health and Welfare Canada . We discuss the preliminary results of a prospect i ve cohort evaluation of the PAL program . This evaluation suggests that the program has some utility in preventing the uptake of tobacco use among young males ; however , its efficacy with females has been negligible . It is clear that prevention programming will have to consider targeting males and females in different ways OBJECTIVES Underst and ing the developmental pathways and sex differences in cigarette smoking behaviors in adolescents has the potential to positively impact substance abuse prevention and to reduce smoking-related health problems . Using data from the Unplugged school-based prevention trial , we investigated different patterns of smoking behavior development among secondary school students in the Czech Republic . METHODS Growth mixture modeling was used to examine different trajectories in cigarette smoking behaviors among male and female students ( N=1874 6th grade rs ; 50.4 % male , mean age 11.8 years at baseline ) participating in the Unplugged school-based r and omized control trial for substance use prevention . RESULTS A two-class model characterized cigarette use as a function of sex and Unplugged intervention status . More rapid cigarette use increases were observed in females ( OR=1.17 , p=0.01 in both rapid/moderate and slow smoking escalator classes ) as compared to males . Further , in both classes , more rapid increases in smoking were observed for the control group as compared to the intervention group ( OR=1.22 , p<0.01 slow escalators ; OR=1.54 , p=0.08 rapid/moderate escalators ) . There was no difference in sex distribution when comparing the two classes ( OR=1.02 , p=0.98 ) . CONCLUSIONS This study adds to a growing literature on developmental and sex differences in cigarette use among adolescents . This research supports additional multi-year prevention strategies aim ed at adolescent females and early treatment programs for adolescent smokers to prevent increasing cigarette use with age 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 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 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 OBJECTIVES The purpose of the study was to determine whether a universal school-based substance abuse prevention program , Take Charge of Your Life ( TCYL ) , prevents or reduces the use of tobacco , alcohol , or marijuana . METHODS Eighty-three school clusters ( representing school districts ) from six metropolitan areas were r and omized to treatment ( 41 ) or control ( 42 ) conditions . Using active consenting procedures , 19,529 seventh grade rs were enrolled in the 5-year study . Self-administered surveys were completed by the students annually . Trained Drug Abuse Resistance Education ( D.A.R.E. ) police officers presented TCYL in seventh and ninth grade s in treatment schools . Analyses were conducted with data from 17,320 students who completed a baseline survey . Intervention outcomes were measured using self-reported past-month and past-year use of tobacco , alcohol , and marijuana when students were in the 11th grade . RESULTS Main effect analyses show a negative program effect for use of alcohol and cigarettes and no effect for marijuana use . Subgroup analyses indicated that the negative effect occurred among nonusers at baseline , and mostly among white students of both genders . A positive program effect was found for students who used marijuana at baseline . Two complementary papers explore the relationship of the targeted program mediators to the use of alcohol , tobacco , and marijuana and specifically for students who were substance-free or who used substances at baseline . CONCLUSIONS The negative impact of the program on baseline nonusers of alcohol and tobacco indicate that TCYL should not be delivered as a universal prevention intervention . The finding of a beneficial effect for baseline marijuana users further supports this conclusion . The programmatic and method ological challenges faced by the Adolescent Substance Abuse Prevention Study ( ASAPS ) and lessons learned offer insights for prevention research ers who will be design ing similar r and omized field trials in the future OBJECTIVES We evaluated the effectiveness of a parent-based add-on component to a school-based intervention to prevent cigarette smoking among African American and Latino middle school youths . METHODS Mother-adolescent dyads ( n=1386 ) were r and omly assigned to 2 groups : ( 1 ) a school-based smoking-prevention intervention or ( 2 ) the same intervention with a parent-based add-on component called Raising Smoke-Free Kids . Mothers in the experimental condition received the parent add-on component . Mothers in the control condition received information on selecting a high school . All adolescents received a version of Project Towards No Tobacco Use ( TNT ) . The primary outcome was a reduction in adolescent cigarette smoking . Follow-up data were obtained from 1096 mother-adolescent dyads at 15 months postintervention . RESULTS At follow-up , the odds of smoking cigarettes were reduced by 42 % for adolescents in the parent add-on condition versus the TNT-only condition . Mothers in the parent add-on condition were more likely than were mothers in the TNT-only condition to set rules about risk-sensitive social activities and to be perceived as trustworthy by their child . Group differences also were found in the frequency and quality of mother-adolescent communication . CONCLUSIONS Including parent add-on components in school-based smoking prevention programs can reduce smoking behavior on the part of inner-city middle school youths 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 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 Most adolescent smoking prevention studies employ design s in which classrooms , schools , school districts , or sometimes whole communities are assigned to treatment conditions while observations are made on individual students . The critical design feature in such community trials is the nesting of intact social groups within treatment conditions . This combination requires that the treatment effect be assessed against the between-group variance ; unfortunately , that variance is usually larger than for r and omly constituted groups and its precision is usually less than that for the within-group variance . These factors often combine to reduce power so that it is almost impossible to detect important treatment effects in an otherwise well design ed and properly executed study . To address these problems , investigators need good estimates of the intraclass correlation for the variables of interest , which together with the number of observations per unit determine the magnitude of the extra variation in the nested design . The purpose of this paper is to describe the methods and results from a study design ed to generate estimates of intraclass correlation for common outcomes in adolescent smoking prevention studies and to discuss the use of these estimates in the planning of new studies OBJECTIVES To implement and to assess the efficacy of a school-based , sport team-centered program to prevent young female high school athletes ' disordered eating and body-shaping drug use . DESIGN AND SETTING Prospect i ve controlled trial in 18 high schools , with balanced r and om assignment by school to the intervention and usual-care control conditions . PARTICIPANTS We enrolled 928 students from 40 participating sport teams . Mean age was 15.4 years , 92.2 % were white , and follow-up retention was 72 % . INTERVENTION The ATHENA ( Athletes Targeting Healthy Exercise and Nutrition Alternative ) curriculum 's 8 weekly 45-minute sessions were incorporated into a team 's usual practice activities . Content was gender-specific , peer-led , and explicitly scripted . Topics included healthy sport nutrition , effective exercise training , drug use and other unhealthy behaviors ' effects on sport performance , media images of females , and depression prevention . MAIN OUTCOME MEASURES We assessed participants by confidential question naire prior to and following their sport season . We determined program effects using an analysis of covariance-based approach within the Generalized Estimating Equation framework . RESULTS Experimental athletes reported significantly less ongoing and new use of diet pills and less new use of athletic-enhancing substances ( amphetamines , anabolic steroids , and sport supplements ) ( P<.05 for each ) . Other health-harming actions also were reduced ( less riding with an alcohol-consuming driver [ P = .05 ] , more seat belt use [ P<.05 ] , and less new sexual activity [ P<.05 ] ) . The ATHENA athletes had coincident positive changes in strength-training self-efficacy ( P<.005 ) and healthy eating behaviors ( P<.001 ) . Reductions occurred in intentions toward future use of diet pills ( P<.05 ) , vomiting to lose weight ( P<.05 ) , and use of tobacco ( P<.05 ) and muscle-building supplements ( P<.005 ) . The program 's curriculum components were altered appropriately ( controlling mood [ P<.005 ] , refusal skills [ P = .05 ] , belief in the media [ P<.005 ] , and perceptions of closest friends ' body-shaping drug use [ P<.001 ] ) . CONCLUSIONS Sport teams are effective natural vehicles for gender-specific , peer-led curricula to promote healthy lifestyles and to deter disordered eating , athletic-enhancing substance use , and other health-harming behaviors |
1,299 | 26,034,938 | A narrative summary of the findings identified that the interventions reported limited success with reducing self report drug use , but did have some impact on re-incarceration rates , but not re-arrest .
In the single comparisons , we found moderate- quality evidence that therapeutic communities determine a reduction in re-incarceration but reported less success for outcomes of re-arrest , moderate quality of evidence and self report drug use . | BACKGROUND This is an up date d version of an original Cochrane review published in Issue 3 2006 ( Perry 2006 ) .
The review represents one from a family of four review s focusing on interventions for drug-using offenders .
This specific review considers interventions aim ed at reducing drug use or criminal activity , or both for drug-using offenders with co-occurring mental illness .
OBJECTIVES To assess the effectiveness of interventions for drug-using offenders with co-occurring mental illness in reducing criminal activity or drug use , or both . | Methamphetamine use is subject to severe criminal punishment in Japan and approximately 22 % of the prison population were confined for violations of the stimulants control law in 2009 . Although the high recidivism rate is also a problem , no systematic treatment has been conducted in prison . Therefore , the development of the prison-based treatment program is necessary . In this study , the prison-based program was developed based on the Matrix Model , which is the cognitive-behavioral treatment for amphetamine users developed in the US . The program was tailored in order to address the treatment needs of the Japanese amphetamine users considering Japanese culture and the prison climate . The r and omized controlled trial was conducted in order to evaluate the effectiveness the Japanese Matrix program ( J-MAT ) . 60 prisoners were r and omly assigned either to the J-MAT or the control groups and those who in the J-MAT group received the program once a week for 12 weeks . The abstinence rate could not be used as the outcome measure because the participants could not be followed after the release from prison due to the legal reasons . Therefore , the psychological variables including coping skills , self-efficacy and motivation were used as outcome measures , which are considered as the important predictive factors of abstinence . 93.3 % of the J-MAT participants completed the program . The coping skills of the treated prisoners were improved significantly after treatment comparing to the control ( F ( 1 , 27 ) = 9.03 , p < .001 ) , however other psychological variables were not significantly improved . The results suggested the effectiveness of the J-MAT because both treatment completion and coping skills are powerful predictors of abstinence . Further study is required and in which the participants should be followed after the completion of treatment in order to compare the relapse rates between the groups and to measure the long-term treatment gain BACKGROUND Despite its effectiveness , methadone maintenance is rarely provided in American correctional facilities . This study is the first r and omized clinical trial in the US to examine the effectiveness of methadone maintenance treatment provided to prisoners with pre-incarceration heroin addiction . METHODS A three-group r and omized controlled trial was conducted between September 2003 and June 2005 . Two hundred eleven Baltimore pre-release inmates who were heroin dependent during the year prior to incarceration were enrolled in this study . Participants were r and omly assigned to the following : counseling only : counseling in prison , with passive referral to treatment upon release ( n=70 ) ; counseling+transfer : counseling in prison with transfer to methadone maintenance treatment upon release ( n=70 ) ; and counseling+methadone : methadone maintenance and counseling in prison , continued in a community-based methadone maintenance program upon release ( n=71 ) . RESULTS Two hundred participants were located for follow-up interviews and included in the current analysis . The percentages of participants in each condition that entered community-based treatment were , respectively , counseling only 7.8 % , counseling+transfer 50.0 % , and counseling+methadone 68.6 % , p<.05 . All pairwise comparisons were statistically significant ( all ps<.05 ) . The percentage of participants in each condition that tested positive for opioids at 1-month post-release were , respectively , counseling only 62.9 % , counseling+transfer 41.0 % , and counseling+methadone 27.6 % , p<.05 , with the counseling only group significantly more likely to test positive than the counseling+methadone group . CONCLUSIONS Methadone maintenance initiated prior to or immediately after release from prison appears to have beneficial short-term impact on community treatment entry and heroin use . This intervention may be able to fill an urgent treatment need for prisoners with heroin addiction histories Exposure to sexual victimization is prevalent among persons with substance use disorders ( SUDs ) . Contingency management ( CM ) treatments utilize concrete and relatively immediate positive reinforcers to retain patients in treatment and reduce substance use , and CM may have particular benefits for patients with histories of sexual victimization . Using data from three r and omized trials of CM ( N = 393 ) , this study evaluated main and interactive effects of sexual abuse history and treatment condition ( st and ard care versus CM ) with respect to during treatment outcomes ( retention , proportion of negative urine sample s su bmi tted , and longest duration of abstinence ) and abstinence at a nine-month follow-up . Compared to patients without sexual abuse histories ( N = 316 ) , those with sexual abuse histories ( N = 77 ) su bmi tted a significantly higher proportion of negative sample s in treatment . In CM , but not in st and ard care , patients with sexual abuse histories achieved significantly longer duration s of abstinence during treatment than those without sexual abuse histories . Although sexual abuse history was not associated with abstinence at nine-month follow-up evaluations , longest duration of abstinence during treatment was significantly associated with this long-term outcome . Results suggest that SUD patients with sexual abuse histories may accrue particular benefits during CM treatment that are associated with long-term abstinence . ( PsycINFO Data base Record ( c ) 2011 APA , all rights reserved ) OBJECTIVE We used growth mixture modeling to examine heterogeneity in treatment response in a secondary analysis of 2 r and omized controlled trials testing multidimensional family therapy ( MDFT ) , an established evidence -based therapy for adolescent drug abuse and delinquency . METHOD The first study compared 2 evidence -based adolescent substance abuse treatments : individually focused cognitive-behavioral therapy and MDFT in a sample of 224 urban , low-income , ethnic minority youths ( average age = 15 years , 81 % male , 72 % African American ) . The second compared a cross-systems version of MDFT ( MDFT-detention to community ) with enhanced services as usual for 154 youths , also primarily urban and ethnic minority ( average age = 15 years , 83 % male , 61 % African American , 22 % Latino ) , who were incarcerated in detention facilities . RESULTS In both studies , the analyses supported the distinctiveness of 2 classes of substance use severity , characterized primarily by adolescents with higher and lower initial severity ; the higher severity class also had greater psychiatric comorbidity . In each study , the 2 treatments showed similar effects in the classes with lower severity/frequency of substance use and fewer comorbid diagnoses . Further , in both studies , MDFT was more effective for the classes with greater overall substance use severity and frequency and more comorbid diagnoses . CONCLUSIONS Results indicate that for youths with more severe drug use and greater psychiatric comorbidity , MDFT produced superior treatment outcomes OBJECTIVES To compare the efficacy of memantine with buprenorphine in the suppression of naloxone-precipitated acute withdrawal in heroin-dependent male subjects in an inpatient setting . SETTING Inpatient unit of tertiary level deaddiction facility . PARTICIPANTS Forty-five treatment-seeking heroin-dependent males . INTERVENTIONS Subjects stabilized on 650 mg of dextropropoxyphene for 5 days were r and omly divided into two groups on the sixth day : group A ( n=25 ) received 20 mg of memantine with buprenorphineplacebo , and group B ( n=20 ) received 2 mg of buprenorphine with memantine placebo . Acute withdrawals were precipitated with naloxone ( 0.4 mg , intravenously ) and were assessed using subjective and objective opioid withdrawal scales ( SOWS and OOWS ) and two separate visual analogue scales ( VASs ) for pain and dysphoria at baseline prior to test drug administration and again after the precipitation of acute withdrawal . MAIN OUTCOME MEASURES Severity ofprecipitated opioid withdrawals . RESULTS Baseline opioid withdrawal symptoms in both groups did not differ significantly . After the precipitation of acute withdrawal , there were no significant differences between subjects in both groups on OOWS and both VASs but showed significant difference on SOWS . When changes in ratings from baseline ( and after naloxone-precipitated acute withdrawal ) were compared between the two groups , a significant difference in the change in SOWS scores was observed with greater decrease in withdrawal scores in the buprenorphine group . CONCLUSIONS Memantine has comparable efficacy to buprenorphine in the suppression of objective signs of naloxone-precipitated acute opioid withdrawal ; however , its role in the suppression of subjective symptoms is debatable Group motivational interviewing ( MI ) interventions that target youth at-risk for alcohol and other drug ( AOD ) use may prevent future negative consequences . Youth in a teen court setting [ n=193 ; 67 % male , 45 % Hispanic ; mean age 16.6 ( SD=1.05 ) ] were r and omized to receive either a group MI intervention , Free Talk , or usual care ( UC ) . We examined client acceptance , and intervention feasibility and conducted a preliminary outcome evaluation . Free Talk teens reported higher quality and satisfaction ratings , and MI integrity scores were higher for Free Talk groups . AOD use and delinquency decreased for both groups at 3 months , and 12-month recidivism rates were lower but not significantly different for the Free Talk group compared to UC . Results contribute to emerging literature on MI in a group setting . A longer term follow-up is warranted CONTEXT Effective alternatives to long waiting lists for entry into methadone hydrochloride maintenance treatment are needed to reduce the complications of continuing heroin dependence and to increase methadone treatment entry . OBJECTIVE To compare the effectiveness of interim methadone maintenance with that of the usual waiting list condition in facilitating methadone treatment entry and reducing heroin and cocaine use and criminal behavior . DESIGN R and omized , controlled , clinical trial using 2 conditions , with treatment assignment on a 3:2 basis to interim maintenance-waiting list control . SETTING A methadone treatment program in Baltimore . PARTICIPANTS A total of 319 individuals meeting the criteria for current heroin dependence and methadone maintenance treatment . INTERVENTIONS Participants were r and omly assigned to either interim methadone maintenance , consisting of an individually determined methadone dose and emergency counseling only for up to 120 days , or referral to community-based methadone treatment programs . MAIN OUTCOME MEASURES Entry into comprehensive methadone maintenance therapy at 4 months from baseline ; self-reported days of heroin use , cocaine use , and criminal behavior ; and number of urine drug test results positive for heroin and cocaine at the follow-up interview conducted at time of entry into comprehensive methadone treatment ( or at 4 months from baseline for participants who did not enter regular treatment ) . RESULTS Significantly more participants assigned to the interim methadone maintenance condition entered comprehensive methadone maintenance treatment by the 120th day from baseline ( 75.9 % ) than those assigned to the waiting list control condition ( 20.8 % ) ( P<.001 ) . Overall , in the past 30 days at follow-up , interim participants reported significantly fewer days of heroin use ( P<.001 ) , had a significant reduction in heroin-positive drug test results ( P<.001 ) , reported spending less money on drugs ( P<.001 ) , and received less illegal income ( P<.02 ) than the waiting list participants . CONCLUSION Interim methadone maintenance results in a substantial increase in the likelihood of entry into comprehensive treatment , and is an effective means of reducing heroin use and criminal behavior among opioid-dependent individuals awaiting entry into a comprehensive methadone treatment program This r and omized trial evaluates whether automated telephony could be used to perform daily assessment s in paroled offenders ( N = 108 ) during their first 30 days after leaving prison . All subjects were called daily and answered assessment questions . Based on the content of their daily assessment s , subjects in the intervention group received immediate feedback and a recommendation by automated telephony , and their probation officers also received a daily report by email . The outcome variables were analyzed using linear mixed models . The intervention group showed greater improvement than the control group in the summary scores ( M = 9.6 , 95 % confidence interval [ CI ] = [ 0.5 , 18.7 ] , p = .038 ) , in mental symptoms ( M = 4.6 , CI = [ 0.2 , 9.0 ] , p = .042 ) , in alcohol drinking ( M = 0.8 , CI = [ 0.1 , 1.4 ] , p = .031 ) , in drug use ( M = 1.0 , CI = [ 0.5 , 1.6 ] , p = .000 ) , and in most stressful daily event ( M = 1.9 , CI = [ 1.1 , 2.7 ] , p = .000 ) . In conclusion , automated telephony may be used to follow up and to give interventions , result ing in reduced stress and drug use , in paroled offenders This study was design ed to fulfill a twofold purpose . First , based on the hope theory framework and previous research , a 16-session hope-based substance abuse treatment program to help female drug abusers achieve a better recovery was developed . Second , ANCOVA was used to test the effectiveness of this treatment model . The participants were 40 female drug offenders who were r and omly assigned into experimental and control groups . The 20 experimental group participants received 16 sessions of hope-based substance abuse treatment whereas the 20 control group members were put on the waiting list for another term of treatment . The results indicated that the members of the two groups had significant differences in their posttest scores for recovery goal setting and pursuing , pathway controlling , adequate energy , knowledge of the changing process , ability to cope , adequate cognition , emotion regulation , and self-esteem Extended-release naltrexone ( XR-NTX ) , an approved treatment for opioid or alcohol dependence , is a once-monthly injectable formulation of naltrexone . Hepatotoxicity concerns have limited its use , necessitating further investigation . This study aims to examine hepatic enzyme levels in participants of 2 r and omized placebo-controlled trials ( RCTs ) of XR-NTX . Hepatic transaminases were measured in 85 patients enrolled in RCTs of XR-NTX among HIV-infected prisoners , transitioning to the community and receiving treatment for either dependence on alcohol ( 52.9 % ) , opioids ( 44.7 % ) or both ( 16.5 % ) . Baseline characteristics included HCV co-infection ( 55.7 % ) , antiretroviral therapy ( 81 % ) , mental illness ( 39 % ) and receiving psychiatric medications ( 34.1 % ) . Levels of aspartate aminotransferase ( AST ) , alanine aminotransferase ( ALT ) and gamma glutamyl transferase ( GGT ) were not statistically different between persons r and omized to placebo ( N=24 ) and XR-NTX ( N=61 ) arms . These results confirm that XR-NTX is safe to use among opioid and alcohol dependent HIV-infected released prisoners receiving ART with high rates of co-morbid HCV infection and mental illness This r and omized controlled pilot study compared a cognitive-behavioral therapy ( Seeking Safety ; SS ) plus treatment-as-usual ( TAU ) to TAU-alone in 49 incarcerated women with substance use disorder ( SUD ) and posttraumatic stress disorder ( PTSD ; full or subthreshold ) . Seeking Safety consisted of a voluntary group treatment during incarceration and individual treatment after prison release . TAU was required in the prison and comprised 180 to 240 hours of individual and group treatment over 6 to 8 weeks . Assessment s occurred at intake , 12 weeks after intake , and 3 and 6 months after release from prison . There were no significant differences between conditions on all key domains ( PTSD , SUD , psychopathology , and legal problems ) ; but both conditions showed significant improvements from intake to later time points on all of these outcomes across time . Secondary analyses at follow-up found trends for SS participants improving on clinician-rated PTSD symptoms and TAU participants worsening on self-reported PTSD symptoms . Also , SS demonstrated continued improvement on psychopathology at 3 and 6 months , whereas TAU did not . However , alcohol use improved more for TAU during follow-up . Satisfaction with SS was high , and a greater number of SS sessions was associated with greater improvement on PTSD and drug use . Six months after release from prison , 53 % of the women in both conditions reported a remission in PTSD . Study limitations include lack of assessment of SS outcomes at end of group treatment ; lack of blind assessment ; omission of the SS case management component ; and possible contamination between the two conditions . The complex needs of this population are discussed Dropout and recidivism from addiction treatment has been found to be associated with individuals ' readiness for change . Motivation for treatment among participants entering the North American Opiate Medication Initiative ( NAOMI ) r and omized controlled trial , which compared heroin assisted treatment ( HAT ) to optimized methadone maintenance treatment ( MMT ) , was assessed . Through multivariate regression , we aim ed to determine whether baseline motivational status was predictive of four treatment outcomes : early dropout , 12-month retention , 12-month response to treatment , and time to discontinuation of treatment . Among the 251 out-of-treatment chronic opioid dependent patients recruited in Montreal , Quebec and Vancouver , British Columbia , 52 % reported having a high level of motivation for treatment . HAT was statistically significantly more effective than MMT on each of the outcomes assessed . Baseline motivational status did not predict retention or time to discontinuation in either HAT or MMT . However , while patients were retained in HAT regardless of motivational status , motivated patients showed a more favourable response to treatment in terms of decreases in crime and illicit drug use . These results suggest that HAT successfully retains opioid dependent patients who otherwise may not have been attracted into existing treatment options , and may enhance the odds of successful rehabilitation among patients motivated for treatment The Transitional Case Management ( TCM ) study , one of the projects of the Criminal Justice Drug Abuse Treatment Studies ( CJ-DATS ) cooperative , was a multi-site r and omized test of whether a strengths-based case management intervention provided during an inmate ’s transition from incarceration to the community increases participation in community substance abuse treatment , enhances access to needed social services , and improves drug use and crime outcomes . As in many intervention studies , TCM experienced a relatively large percentage of treatment-group participants who attended few or no scheduled sessions . The paper discusses issues with regard to participation in community case management sessions , examines patterns of session attendance among TCM participants , and analyzes client and case manager characteristics that are associated with number of sessions attended and with patterns of attendance . The average number of sessions ( out of 12 ) attended was 5.7 . Few client or case manager characteristics were found to be significantly related to session attendance . Clinical and research implication s of the findings and of adherence in case management generally are discussed Jail diversion and forensic community treatment programs have proliferated over the past decade , far outpacing evidence regarding their efficacy . The current study reports findings from a r and omized clinical trial conducted in California for frequent jail users with serious mental illness that compares a forensic assertive community treatment ( FACT ) intervention with treatment as usual ( TAU ) . Outcomes are reported at 12 and 24 months post-r and omization for criminal justice outcomes , behavioral health services and costs . At 12 months , FACT vs. TAU participants had fewer jail bookings , greater outpatient contacts , and fewer hospital days than did TAU participants . Results of zero-inflated negative binomial regression found that FACT participants had a higher probability of avoiding jail , although once jailed , the number of jail days did not differ between groups . Increased outpatient costs result ing from FACT outpatient services were partially offset by decreased inpatient and jail costs . The findings for the 24 month period followed the same pattern . These findings provide additional support for the idea that providing appropriate behavioral health services can reduce criminal justice involvement OBJECTIVE Motivational interviewing to reduce alcohol and marijuana use among incarcerated adolescents was evaluated . METHOD Adolescents ( N = 162 , 84 % male ; M = 17.10 years old ) were r and omly assigned to receive motivational interviewing or relaxation training , with follow-up assessment 3 months after release . RESULTS Compared with those who received relaxation training , adolescents who received motivational interviewing had lower rates of alcohol and marijuana use at follow-up , with some evidence for moderating effects of depression . At low levels of depression , adolescents who received motivational interviewing had lower rates of use . Adolescents who received relaxation training and who had high levels of depressive symptoms early in incarceration showed less use at follow-up than those low in depressive symptoms who received relaxation training . CONCLUSIONS This brief motivational interviewing intervention during incarceration reduces alcohol and marijuana use after release . In addition , depressive symptoms early in incarceration should be considered in treating these adolescents , but more work is needed to extend follow-up period and account for the impact of depression on outcomes Jail recidivists with serious mental illness and substance use disorders were treated in an in-custody setting and then r and omly assigned to either a high fidelity Integrated Dual Disorders Treatment program ( 103 participants ) or to service as usual ( 79 participants ) . Outcomes were tracked an average of 18 months from program entry at the termination of the initial incarceration . A reduction in jail days from baseline to study period was significant for both groups . The pre to post reduction for arrests and total convictions was significant in the experimental group but not the control group . However , during the study period , differences between experimental and control groups in arrests , convictions and jail days were not statistically significant . Experimental participants had lower study period psychiatric inpatient and crisis utilization and greater outpatient utilization than did control group participants . The groups did not differ with regard to total institutional days . Experimental group attrition was relatively high Federal probationers or parolees with a history of opioid addiction were referred by themselves or their probation/parole officer for a naltrexone treatment study . Participation was voluntary and subjects could drop out of the study at any time without adverse consequences . Following orientation and informed consent , 51 volunteers were r and omly assigned in a 2:1 ratio to a 6-month program of probation plus naltrexone and brief drug counseling , or probation plus counseling alone . Naltrexone subjects received medication and counseling twice a week ; controls received counseling at similar intervals . All therapy and medication were administered in an office located adjacent to the federal probation department . Fifty-two percent of subjects in the naltrexone group continued for 6 months and 33 % remained in the control group . Opioid use was significantly lower in the naltrexone group . The overall mean percent of opioid positive urine tests among the naltrexone subjects was 8 % , versus 30 % for control subjects ( p < .05 ) . Fifty-six percent of the controls and 26 % of the naltrexone group ( p < .05 ) had their probation status revoked within the 6-month study period and returned to prison . Treatment with naltrexone and brief drug counseling can be integrated into the Federal Probation/Parole system with favorable results on both opioid use and re-arrest rates INTRODUCTION Comorbid substance related disorders are a major health problem for patients in opioid maintenance treatment ( OMT ) . It was investigated whether a reinforcement scheme adapted to the regulatory and financial restrictions of routine treatment reduces concomitant drug use . METHODS OMT patients from 7 clinics who were using cocaine , benzodiazepines , heroin or amphetamines were r and omly allocated to either treatment as usual ( n = 64 ) or treatment with an additional escalating reinforcement scheme ( n = 72 ) in which a patient 's number of weekly take-home dosages was increased after 1 , 4 , 8 and 12 consecutive weeks with drug-free urine specimens . Trial duration was 26 weeks . RESULTS Completion rates were 64 % for controls and 62.5 % in the experimental group . Mean number of drug-free weeks was 11.3 ( SD 8.5 ) for the control group and 9.8 ( 8.9 ) for the experimental group ( p = 0.30 ) . CONCLUSION The intervention was not effective compared to routine treatment . Additional features might be necessary to achieve an effect , e.g. a higher frequency of urine sampling or use of other reinforcers . It has to be further investigated how interventions which have been proven effective in experimental studies can successfully be adapted to routine care conditions Evaluated the effectiveness of juvenile drug court for 161 juvenile offenders meeting diagnostic criteria for substance abuse or dependence and determined whether the integration of evidence -based practice s enhanced the outcomes of juvenile drug court . Over a 1-year period , a four-condition r and omized design evaluated outcomes for family court with usual community services , drug court with usual community services , drug court with multisystemic therapy , and drug court with multisystemic therapy enhanced with contingency management for adolescent substance use , criminal behavior , symptomatology , and days in out-of-home placement . In general , findings supported the view that drug court was more effective than family court services in decreasing rates of adolescent substance use and criminal behavior . Possibly due to the greatly increased surveillance of youths in drug court , however , these relative reductions in antisocial behavior did not translate to corresponding decreases in rearrest or incarceration . In addition , findings supported the view that the use of evidence -based treatments within the drug court context improved youth substance-related outcomes . Clinical and policy implication s of these findings are discussed OBJECTIVE This study examined the relationships between treatment fidelity and treatment outcomes in a community-based trial of a 12-Step Facilitation ( TSF ) intervention . METHOD In a prior multi-site r and omized clinical trial , 234 participants in 10 outpatient drug treatment clinics were assigned to receive the Stimulant Abuser Groups to Engage in 12-Step ( STAGE-12 ) intervention . A secondary analysis review ed and coded all STAGE-12 sessions for fidelity to the protocol , using the Twelve Step Facilitation Adherence Competence Empathy Scale ( TSF ACES ) . Linear mixed-effects models tested the relationship between three fidelity measures ( adherence , competence , empathy ) and six treatment outcomes ( number of days of drug use and five Addiction Severity Index ( ASI ) composite scores ) measured at 3 months post-baseline . RESULTS Adherence , competence and empathy were robustly associated with improved employment status at follow up . Empathy was inversely associated with drug use , as was competence in a non-significant trend ( p=.06 ) . Testing individual ASI drug composite score items suggested that greater competence was associated with fewer days of drug use and , at the same time , with an increased sense of being troubled or bothered by drug use . CONCLUSIONS Greater competence and empathy in the delivery of a TSF intervention were associated with better drug use and employment outcomes , while adherence was associated with employment outcomes only . Higher therapist competence was associated with lower self-report drug use , and also associated with greater self-report concern about drug use . The nature of TSF intervention may promote high levels of concern about drug use even when actual use is low This study examined benefits of methadone maintenance among prerelease prison inmates . Incarcerated males with preincarceration heroin dependence ( n = 197 ) were r and omly assigned to ( a ) group educational counseling ( counseling only ) ; ( b ) counseling , with opportunity to begin methadone maintenance on release ( counseling + transfer ) ; or ( c ) counseling and methadone maintenance in prison , with opportunity to continue methadone maintenance on release ( counseling + methadone ) . At 90-day follow-up , counseling + methadone participants were significantly more likely than counseling-only and counseling + transfer participants to attend drug treatment ( p = .0001 ) and less likely to be reincarcerated ( p = .019 ) . Counseling + methadone and counseling + transfer participants were significantly less likely ( all ps < .05 ) to report heroin use , cocaine use , and criminal involvement than counseling-only participants . Follow-up is needed to determine whether these findings hold over a longer period AIMS Recent studies have demonstrated the efficacy of both methadone and buprenorphine when used with opioid dependent men transitioning from prison to the community , but no studies have been conducted with women in the criminal justice ( CJ ) system . The aim of this study was to determine the efficacy of buprenorphine for relapse prevention among opioid dependent women in the CJ system transitioning back to the community . METHODS 36 women under CJ supervision were recruited from an inpatient drug treatment facility that treats CJ individuals returning back to the community . Nine were enrolled in an open label buprenorphine arm then 27 were r and omized to buprenorphine ( n=15 ) or placebo ( n=12 ; double-blind ) . All women completed baseline measures and started study medication prior to release . Participants were followed weekly , provided urine drug screens ( UDS ) , received study medication for 12 weeks , and returned for a 3-month follow-up . Intent-to-treat analyses were performed for all time points through 3 month follow-up . RESULTS The majority of participants were Caucasian ( 88.9 % ) , young ( M±SD=31.8±8.4 years ) , divorced/separated ( 59.2 % ) women with at least a high school/GED education ( M±SD=12±1.7 years ) . GEE analyses showed that buprenorphine was efficacious in maintaining abstinence across time compared to placebo . At end of treatment , 92 % of placebo and 33 % of active medication participants were positive for opiates on urine drug screen ( Chi-Square=10.9 , df=1 ; p<0.001 ) . However , by the three month follow-up point , no differences were found between the two groups , with 83 % of participants at follow-up positive for opiates . CONCLUSIONS Women in the CJ system who received buprenorphine prior to release from a treatment facility had fewer opiate positive UDS through the 12 weeks of treatment compared to women receiving placebo . Initiating buprenorphine in a controlled environment prior to release appears to be a viable strategy to reduce opiate use when transitioning back to the community CONTEXT Contingency management interventions that provide tangible incentives based on objective indicators of drug abstinence are efficacious in improving outcomes in substance abusers , but these treatments have rarely been implemented in community-based setting s. OBJECTIVE To evaluate the efficacy of an abstinence-based contingency management intervention as an addition to usual care in community treatment setting s. DESIGN R and om assignment to usual care or usual care plus abstinence-based incentives for 12 weeks . SETTING Eight community-based outpatient psychosocial drug abuse treatment programs . PARTICIPANTS A total of 415 cocaine or methamphetamine users beginning outpatient substance abuse treatment . INTERVENTION All participants received st and ard care , and those assigned to the abstinence-based incentive condition also earned chances to win prizes for su bmi tting substance-free urine sample s ; the chances of winning prizes increased with continuous time abstinent . MAIN OUTCOME MEASURES Retention , counseling attendance , total number of substance-free sample s provided , percentage of stimulant- and alcohol-free sample s su bmi tted , and longest duration of confirmed stimulant abstinence . RESULTS Participants assigned to the abstinence-based incentive condition remained in treatment for a mean + /- SD of 8.0 + /- 4.2 weeks and attended a mean + /- SD of 19.2 + /- 16.8 counseling sessions compared with 6.9 + /- 4.4 weeks and 15.7 + /- 14.4 sessions for those assigned to the usual care condition ( P<.02 for all ) . Participants in the abstinence-based incentive condition also su bmi tted significantly more stimulant- and alcohol-free sample s ( P<.001 ) . The abstinence-based incentive group was significantly more likely to achieve 4 , 8 , and 12 weeks of continuous abstinence than the control group , with odds ratios of 2.5 , 2.7 , and 4.5 , respectively . However , the percentage of positive sample s su bmi tted was low overall and did not differ between conditions . CONCLUSION The abstinence-based incentive procedure , which provided a mean of 203 dollars in prizes per participant , was efficacious in improving retention and associated abstinence outcomes An open trial design was used to examine the implementation and effectiveness of a cognitive-behavioral intervention ( Seeking Safety ) for comorbid post-traumatic stress disorder ( PTSD ) and substance use disorder ( SUD ) for incarcerated women with Axis I mental disorders who self-referred for specialty trauma treatment . The study sample was female inmates aged 18 and old who were primarily minority , had experienced childhood-based trauma , committed violent crimes , had a serious mental illness , and resided in maximum , medium , and minimum compounds of a women 's prison . A total of 74 women completed the group intervention , with the average attending 23 of the 28 sessions ( 82 % ) . Implementation feasibility was demonstrated by the ability to recruit , screen , assign , and retain participation . Effectiveness was supported by changes pre-post intervention on the PTSD Checklist ( ES=0.56 ) and Global Severity Index ( ES=0.47 ) . Of the 19 completers with PCL scores of 50 or higher pre-intervention , 16 ( 84 % ) had scores below 50 , the " cut score " consistent with or supportive of a PTSD diagnosis . Three-quarters or more of participants reported that Seeking Safety was helpful in each of the following areas : overall , for traumatic stress symptoms , for substance use , to focus on safety , and to learn safe coping skills . Future directions include the need for larger scale r and omized controlled trials in medium or maximum security prisons and fidelity evaluations of non- research dissemination efforts BACKGROUND Cocaine abuse and dependence continue to be widespread . Currently , there are no pharmacotherapies shown to be effective in the treatment of cocaine dependence . METHODS A 33-week outpatient clinical trial of fluoxetine ( 60 mg/day , po ) for cocaine dependence that incorporated abstinence-contingent voucher incentives was conducted . Participants ( N = 145 ) were both cocaine and opioid dependent and treated with methadone . A stratified r and omization procedure assigned subjects to one of four conditions : fluoxetine plus voucher incentives ( FV ) , placebo plus voucher incentives ( PV ) , fluoxetine without vouchers ( F ) , and placebo without vouchers ( P ) . Dosing of fluoxetine/placebo was double blind . Primary outcomes were treatment retention and cocaine use based on thrice-weekly urine testing . RESULTS The PV group had the longest treatment retention ( M = 165 days ) and lowest probability of cocaine use . The adjusted predicted probabilities of cocaine use were 65 % in the P group , 60 % in the F group , 56 % in the FV group , and 31 % in the PV group . CONCLUSIONS Fluoxetine was not efficacious in reducing cocaine use in patients dually dependent on cocaine and opioids This study is the first experimental trial to evaluate the effectiveness of a Web-based behavioral intervention when deployed in a model where it partially substituted for st and ard counseling in a community-based specialty addiction treatment program . New opioid-dependent intakes in methadone maintenance treatment ( n=160 ) were r and omly assigned for 12months to either : ( 1 ) st and ard treatment or ( 2 ) reduced st and ard treatment plus a Web-based psychosocial intervention , the Therapeutic Education System ( TES ) . Results demonstrated that replacing a portion of st and ard treatment with TES result ed in significantly greater rates of objective ly measured opioid abstinence ( 48 % vs. 37 % abstinence across all study weeks ; F(1 , 158)=5.90 , p<.05 and 59 % vs. 43 % abstinence on weeks participants provided urine sample s for testing ; F(1 , 158)=8.81 , p<.01 ) . This result was robust and was evident despite how opioid abstinence was operationally defined and evaluated . The potential implication s for service delivery models within substance abuse treatment programs and other healthcare entities are discussed AIMS The objective is to estimate cost , net social cost and cost-effectiveness in a clinical trial of extended buprenorphine-naloxone ( BUP ) treatment versus brief detoxification treatment in opioid-dependent youth . DESIGN Economic evaluation of a clinical trial conducted at six community out-patient treatment programs from July 2003 to December 2006 , who were r and omized to 12 weeks of BUP or a 14-day taper ( DETOX ) . BUP patients were prescribed up to 24 mg per day for 9 weeks and then tapered to zero at the end of week 12 . DETOX patients were prescribed up to 14 mg per day and then tapered to zero on day 14 . All were offered twice-weekly drug counseling . PARTICIPANTS 152 patients aged 15 - 21 years . MEASUREMENTS Data were collected prospect ively during the 12-week treatment and at follow-up interviews at months 6 , 9 and 12 . FINDINGS The 12-week out-patient study treatment cost was $ 1514 ( P < 0.001 ) higher for BUP relative to DETOX . One-year total direct medical cost was only $ 83 higher for BUP ( P = 0.97 ) . The cost-effectiveness ratio of BUP relative to DETOX was $ 1376 in terms of 1-year direct medical cost per quality -adjusted life year ( QALY ) and $ 25,049 in terms of out-patient treatment program cost per QALY . The acceptability curve suggests that the cost-effectiveness ratio of BUP relative to DETOX has an 86 % chance of being accepted as cost-effective for a threshold of $ 100,000 per QALY . CONCLUSIONS Extended BUP treatment relative to brief detoxification is cost effective in the US health-care system for the outpatient treatment of opioid-dependent youth Correctional systems nationwide have increasingly turned to therapeutic community ( TC ) programs for the treatment of addiction in prisons . TC treatment , with modifications , has shown considerable promise in treating offenders who have co-occurring mental and substance use disorders , a group that has a mounting prevalence in prison population s. This article reports data from a study that r and omly assigned male inmates with mental illness and chemical abuse ( MICA ) disorders ( n = 139 ) to either a Modified TC ( MTC ) or a comparison group . Analyses revealed that the MTC group had significantly greater declines in alcohol and drug use at 12-months post-prison release . Additional analysis related positive substance use outcomes to reduced contact with the justice system and self-reported criminal activity . Implication s for treatment and policy are discussed Abstract Treating cocaine use by opiate-dependent clients in methadone programs is a well-documented challenge . Both behavioral ( contingency management ) and cognitive ( relapse prevention ) interventions have shown promise in helping engage these clients in treatment . In this study , the effectiveness of combining contingency management with a cocaine-specific relapse prevention counseling module was examined . Sixty-one cocaine-using methadone clients were r and omly assigned to one of four treatment conditions to participate in the eight-week intervention and eight-week follow-up period . Using analysis of variance ( ANOVA ) , differences in cocaine use and treatment retention were examined . Contingency management was significantly related to reductions in cocaine use and the counseling module was positively related to six-month retention rates . Both interventions were associated with positive treatment response but the effects were reflected in different behavioral outcomes This article reports recent findings from a program of experimental research examining the effects of adapting judicial supervision to the risk level of drug-abusing offenders . Prior studies revealed that high-risk participants with ( 1 ) antisocial personality disorder or ( 2 ) a history of drug abuse treatment performed significantly better in drug court when they were scheduled to attend frequent , bi-weekly judicial status hearings in court . Low-risk participants performed equivalently regardless of the schedule of court hearings . The current study prospect ively matched misdemeanor drug court clients to the optimal schedule of court hearings based upon an assessment of their risk status , and compared outcomes to those of clients r and omly assigned to the st and ard schedule of court hearings . Results confirmed that high-risk participants graduated at a higher rate , provided more drug-negative urine specimens at 6 months post-admission , and reported significantly less drug use and alcohol intoxication at 6 months post-admission when they were matched to bi-weekly hearings as compared to the usual schedule of hearings . These findings yield practical information for enhancing the efficacy and cost-efficiency of drug court services . Directions for future research on adaptive programming for drug offenders are discussed Background Traumatic experiences and , more specifically , posttraumatic stress disorder ( PTSD ) are highly prevalent among substance use disorder ( SUD ) patients . This comorbidity is associated with worse treatment outcomes in substance use treatment programs and more crisis interventions . International guidelines advise an integrated approach to the treatment of trauma related problems and SUD . Seeking Safety is an integrated treatment program that was developed in the United States . The aim of the current study is to test the efficacy of this program in the Netherl and s in an outpatient SUD population . Methods / Design A r and omized controlled trial ( RCT ) will be used to test the efficacy of Seeking Safety compared to Cognitive Behavioral Therapy ( CBT ) in a population of SUD out patients . Each treatment will consist of 12 group sessions . The primary outcome measure will be substance use severity . Secondary outcome measures are PTSD and trauma symptoms , coping skills , functioning , and cognitions . Question naires will be administered at the start of treatment , at the end of treatment ( three months after the start of treatment ) and at follow-up ( six months after the start of treatment ) . Discussion This study protocol presents a RCT in which the efficacy of an integrated treatment for comorbid PTSD and SUD , Seeking Safety , is evaluated in a SUD outpatient population compared to CBT . It is expected that the intervention group will show significantly more improvement in substance use severity compared to the control group at end-of-treatment and at follow-up . Furthermore , a lower drop-out rate is expected for the intervention group . If the intervention proves to be effective , it can be implemented . A cost-effectiveness analysis will be conducted to evaluate the two treatments . Trial registration The protocol for this study is registered with the Netherl and s Trial Register with number NTR3084 and approved by the local medical ethical committee ( METC\11270.haa ) PURPOSE This study assesses the impact of REAL MEN ( Returning Educated African-American and Latino Men to Enriched Neighborhoods ) , an intervention design ed to reduce drug use , risky sexual behavior and criminal activity among 16 - 18-year-old males leaving New York City jails . METHODS Participants ( N = 552 ) were recruited in city jails and r and omly assigned to receive an intensive 30-hour jail/community-based intervention or a single jail-based discharge planning session . All participants were also referred to optional services at a community-based organization ( CBO ) . One year after release from jail , 397 ( 72 % ) participants completed a follow-up interview . Logistic and ordinary least squares regression was used to evaluate the impact of the intervention on drug use , risky sexual behavior , criminal justice involvement , and school/work involvement post release . RESULTS Assignment to REAL MEN and , independently , use of CBO services , significantly reduced the odds of substance dependence ( odds ratio [ OR ] = .52 , p ≤ .05 ; OR = .41 , p ≤ .05 , respectively ) 1 year after release . Those assigned to the intervention spent 29 fewer days in jail compared with the comparison group ( p ≤ .05 ) . Compared to non-CBO visitors , those who visited the CBO were more likely to have attended school or found work in the year after release ( OR = 2.02 , p ≤ .01 ) . CONCLUSIONS Jail and community services reduced drug dependence 1 year after release and the number of days spent in jail after the index arrest . While these findings suggest that multifaceted interventions can improve outcomes for young men leaving jail , rates of drug use , risky sexual behavior , and recidivism remained high for all participants after release from jail , suggesting the need for additional policy and programmatic interventions Our goal was to determine whether treatment of depressive symptoms with escitalopram during buprenorphine treatment for opioid dependence would improve treatment retention compared to placebo in a 12-week , r and omized , double-blind trial . Treatment dropout was defined as missing seven consecutive buprenorphine dosing days . Participants were 76 % male , 80 % non-Hispanic Caucasian , and 64 % heroin users . At baseline , the mean Beck Depression Inventory II ( BDI-II ) score was 28.4 ( + /-9.7 ) . Sixty-one percent of participants completed the 12-week buprenorphine protocol . Dropout rates were 33.3 % and 44.0 % among those r and omized to escitalopram or placebo , respectively ( p = .19 ) . Relative to baseline , mean BDI-II scores were significantly lower at all follow-up assessment s , but the Treatment x Time interaction effect was not statistically significant ( p = .18 ) . Participants r and omized to escitalopram also did not have a significantly lower likelihood of testing positive for either opiates or other drugs during follow-up . Depressive symptoms often resolved with buprenorphine treatment , and the immediate initiation of escitalopram does not improve treatment retention , depression outcomes , or illicit drug use . Clinicians should determine the need for antidepressant treatment later in buprenorphine care This study , the largest r and omized controlled trial of treatment for major depressive disorder ( MDD ) in an incarcerated population to date , wave-r and omized 38 incarcerated women ( 6 waves ) with MDD who were attending prison substance use treatment to adjunctive group interpersonal psychotherapy ( IPT ) for MDD or to an attention-matched control condition . Intent-to-treat analyses found that IPT participants had significantly lower depressive symptoms at the end of 8 weeks of in-prison treatment than did control participants . Control participants improved later , after prison release . IPT 's rapid effect on MDD within prison may reduce serious in-prison consequences of MDD Objectives Despite evidence that treatment is effective in reducing recidivism among inmates with substance use problems , scarce re sources mean that few of those in need of treatment actually receive it . Computerized substance abuse interventions could be used to exp and access to treatment in prisons without placing an undue burden on re sources . The major aim of the study was to compare treatment conditions in terms of their service utilization , skills acquisition , and treatment satisfaction . Methods The study recruited men and women with substance use disorders from 10 prisons in 4 states . In an open label clinical trial , 494 subjects were r and omly assigned either to the Experimental condition , a computerized drug treatment intervention , the Therapeutic Education System ( TES ; n = 249 ) , or to the Control condition , St and ard Care ( n = 245 ) . Chi-square tests compared groups on categorical variables and independent sample s t tests were used for interval level continuous variables . Results Initial evidence demonstrated : ( 1 ) comparable group rates of session attendance and high rates of TES module completion for experimental subjects ; ( 2 ) comparable group gains in the development of coping skills ; and ( 3 ) a more favorable view of TES than of St and ard Care . Conclusions Collectively , these results show that a computerized intervention , such as TES , can be implemented successfully in prison . Given the barriers to the delivery of substance abuse treatment typically encountered in correctional setting s , computerized interventions have the potential to fill a significant treatment gap and are particularly well suited to inmates with mild to moderate substance use disorders who often are not treated Background Many opiate users entering British prisons require prescribed medication to help them achieve abstinence . This commonly takes the form of a detoxification regime . Previously , a range of detoxification agents have been prescribed without a clear evidence base to recommend a drug of choice . There are few trials and very few in the prison setting . This study compares dihydrocodeine with buprenorphine . Methods Open label , pragmatic , r and omised controlled trial in a large rem and prison in the North of Engl and . Ninety adult male prisoners requesting an opiate detoxification were r and omised to receive either daily sublingual buprenorphine or daily oral dihydrocodeine , given in the context of routine care . All participants gave written , informed consent . Reducing regimens were within a st and ard regimen of not more than 20 days and were at the discretion of the prescribing doctor . Primary outcome was abstinence from illicit opiates as indicated by a urine test at five days post detoxification . Secondary outcomes were collected during the detoxification period and then at one , three and six months post detoxification . Analysis was undertaken using relative risk tests for categorical data and unpaired t-tests for continuous data . Results 64 % of those approached took part in the study . 63 men ( 70 % ) gave a urine sample at five days post detoxification . At the completion of detoxification , by intention to treat analysis , a higher proportion of people allocated to buprenorphine provided a urine sample negative for opiates ( abstinent ) compared with those who received dihydrocodeine ( 57 % vs 35 % , RR 1.61 CI 1.02–2.56 ) . At the 1 , 3 and 6 month follow-up points , there were no significant differences for urine sample s negative for opiates between the two groups . Follow up rates were low for those participants who had subsequently been released into the community . Conclusion These findings would suggest that dihydrocodeine should not be routinely used for detoxification from opiates in the prison setting . The high relapse rate amongst those achieving abstinence would suggest the need for an increased emphasis upon opiate maintenance programmes in the prison setting .Trial registration Current Controlled Trials IS RCT OBJECTIVE Although several treatments for adolescent substance abuse have been identified as promising by review ers and federal agencies , treatment effects extending beyond 12 months have not been demonstrated in r and omized clinical trials . The primary purpose of this report was to examine the 4-year outcomes of an evidence -based treatment of substance-abusing juvenile offenders . METHOD Eighty of 118 substance-abusing juvenile offenders participated in a follow-up 4 years after taking part in a r and omized clinical trial comparing multisystemic therapy ( MST ) with usual community services . A multi method ( self-report , biological , and archival measures ) assessment battery was used to measure the criminal behavior , illicit drug use , and psychiatric symptoms of the participating young adults . RESULTS Analyses demonstrated significant long-term treatment effects for aggressive criminal activity ( 0.15 versus 0.57 convictions per year ) but not for property crimes . Findings for illicit drug use were mixed , with biological measures indicating significantly higher rates of marijuana abstinence for MST participants ( 55 % versus 28 % of young adults ) . Long-term treatment effects were not observed for psychiatric symptoms . CONCLUSIONS Findings provide some support for the long-term effectiveness of an evidence d-based family-oriented treatment of substance-abusing juvenile offenders . The clinical , research , and policy implication s of these findings are noted BACKGROUND The benefits of integrating substance abuse and psychiatric care may be limited by poor service utilization . This r and omized clinical trial evaluated the efficacy of using contingency management to improve utilization of psychiatric services co-located and integrated within a community-based methadone maintenance treatment program . METHODS Opioid-dependent out patients ( n=125 ) with any current psychiatric disorder were r and omly assigned to : ( 1 ) reinforced on-site integrated care ( ROIC ) , with vouchers ( worth $ 25.00 ) contingent on full adherence to each week of scheduled psychiatric services ; or ( 2 ) st and ard on-site integrated care ( SOIC ) . All participants received access to the same schedule of psychiatrist and mental health counseling sessions for 12-weeks . RESULTS ROIC participants attended more overall psychiatric sessions at month 1 ( M=7.53 vs. 3.97 , p<.001 ) , month 2 ( M=6.31 vs. 2.81 , p<.001 ) , and month 3 ( M=5.71 vs. 2.44 , p<.001 ) . Both conditions evidence d reductions in psychiatric distress ( p<.001 ) and similar rates of drug-positive urine sample s. No differences in study retention were observed . CONCLUSIONS These findings suggest that contingency management can improve utilization of psychiatric services scheduled within an on-site and integrated treatment model . Delivering evidence d-based mental health counseling , or modifying the contingency plan to include illicit drug use , may be required to facilitate greater changes in psychiatric and substance abuse outcomes Substantial evidence indicates that drug courts can be superior to traditional probation programs for enhancing treatment retention and reducing substance use and crime among drug offenders . Few studies have isolated the effects of the hypothesized " key components " of drug courts to determine their contributions to outcomes . This article presents outcomes at 6 and 12 months post-admission for misdemeanor drug court clients who were r and omly assigned to different dosages of judicial status hearings . Although earlier work revealed superior during-treatment effects for high-risk participants who were assigned to more frequent bi-weekly hearings , those effects did not extend post-treatment . The results did reveal significant pre-to-post improvements for participants , as a whole , in self-reported drug use , alcohol use , and criminal recidivism ; however , lacking a no-drug court control condition , it is not possible to discern the magnitude of the effect of the drug court program . Approximately , half of the participants resumed drug or alcohol use within 12 months of admission to drug court , and approximately 10 - 15 % resumed illegal activities . These findings lend credence to the potential effectiveness of drug courts ; however , continuing-care strategies are required to extend the effects of drug courts beyond the initial active phases of the program China faces the challenge of dual epidemics of drug use and HIV/AIDS . Despite the high relapse rate among heroin addicts released from compulsory rehabilitation facilities , there are few programs available in China to assist these addicts in the community . We pilot-tested in China a Recovery Management Intervention ( RMI ) program design ed to facilitate early detection of relapse and prompt linkage from compulsory rehabilitation to the community and , if participants relapse , to community-based methadone maintenance treatment ( MMT ) programs . One hundred heroin addicts were r and omly assigned to either the St and ard Care group ( n = 50 ) or the RMI group ( n = 50 ) . At the end of the 3-month trial , participants in the RMI group , relative to the st and ard care group , demonstrated positive outcomes in recidivism due to relapse ( 0 vs. 6 % , p = .08 ; d = 0.354 ) , MMT participation ( 8 % vs. 0 , p = 0.06 ; d = 0.417 ) , and employment ( 33 % vs. 2 % , p < .001 ; d = 0.876 ) , although no difference was found in urine testing results ( 8.5 % vs. 8.7 % ; d = 0.013 ) among interviewed participants . These pilot study results were based on a small sample size and short-term observation , suggesting the need for more research to further improve and test RMI effectiveness with larger sample s over a longer period of time in order to provide evidence in support of RMI as an effective strategy for community reintegration among addicts released from rehabilitation facilities in China BACKGROUND Marijuana use is common in patients seeking treatment for cocaine use . Nevertheless , few studies have examined effects of marijuana use on treatment outcomes in general , and even fewer with respect to contingency management ( CM ) treatment , which has been criticized for potentially increasing non-reinforced drug use . METHODS Data from three r and omized clinical trials of CM versus st and ard treatment ( ST ) in cocaine-abusing patients were examined ( Petry et al. , 2004 , 2005a , 2006a ; N=393 ) to assess effects of pretreatment marijuana use on outcomes . Patients were divided into two groups : ( 1 ) no self-reported marijuana use ( No Pre-M ; n=315 ) and ( 2 ) any self-reported marijuana use ( Pre-M ; n=78 ) in the 30 days pretreatment . RESULTS CM was especially efficacious in enhancing retention in Pre-M patients such that retention nearly doubled among Pre-M patients assigned to CM versus those assigned to ST . In contrast , CM exerted only modest benefits on retention in No Pre-M patients . Pretreatment marijuana use was not related to during-treatment abstinence from cocaine , opioids , and alcohol , or abstinence at a Month 9 follow-up . However , CM treatment and longest duration of abstinence achieved during treatment were significant predictors of Month 9 abstinence . Pre-M patients also evidence d more improvements in drug problems over time when r and omized to CM . CONCLUSIONS CM was especially efficacious in facilitating retention and improving severity of drug-related problems in those who used marijuana in the month before initiating treatment This study examines the efficacy of providing Enhanced Abbreviated or St and ard Inpatient treatment and Outpatient treatment to drug-abusing clients . The experiment r and omly assigned 412 clients to two therapeutic community programs , which differed primarily in planned duration . This study addressed limitations of prior research , as it used r and om assignment of clients to treatment programs , achieved high follow-up rates and used objective measures of drug use and criminal history . Self-reports and objective measures of criminal activity and substance abuse were collected at pre- and posttreatment interviews . Completing the entire 12-month program ( inpatient and outpatient ) was more important than duration of inpatient program attended . Regardless of program , completers had substantial reductions in posttreatment drug abuse and arrests . A 12-month course of treatment including at least 6 months in a therapeutic community followed by outpatient treatment can produce marked reductions in drug abuse and crime among persons who complete both phases Abstract In prior research , Katz et al.1 found that role induction ( RI ) improved engagement for substance dependent clients relative to st and ard outpatient treatment orientation . The current study replicates and extends these findings to an examination of long-term outcomes . Substance dependent clients entering outpatient drug-free treatment ( N = 353 ) were r and omly assigned to RI or to St and ard ( ST ) orientation followed by routine clinic treatment . Measures of employment , crime , and substance use were collected at intake and at six- and 12-months post-intake . Controlling for baseline differences in substance use , results partially replicated our earlier findings of better engagement for RI , as compared to ST participants ; more RI than ST participants attended at least one post-orientation counseling session . RI improved 12-month substance use outcome relative to ST . The potential gain in retention and in reduced substance use at follow-up associated with a single RI session , recommend this strategy for further development and study Background The epidemics of incarceration , substance use disorders ( SUDs ) , and infectious diseases are inextricably intertwined , especially in the Former Soviet Union ( FSU ) . Few objective data documenting this relationship regionally are available . We therefore conducted a comprehensive , representative country-wide prison health survey in Ukraine , where one of the world ’s most volatile HIV epidemics persists , in order to address HIV prevention and treatment needs . Methods A nation-wide , multi-site r and omly sample d biobehavioral health survey was conducted in four Ukrainian regions in 13 prisons among individuals being released within six months . After consent , participants underwent st and ardized health assessment surveys and serological testing for HIV , viral hepatitis , and syphilis . Results Of the 402 participants ( mean age = 31.9 years ) , 20.1 % were female . Prevalence of HIV , HCV , HBV , and syphilis was 19.4 % ( 95 % CI = 15.5%–23.3 % ) , 60.2 % ( 95 % CI = 55.1%–65.4 % ) , 5.2 % ( 95 % CI = 3.3%–7.2 % ) , and 10 % ( 95 % CI = 7.4%–13.2 % ) , respectively , with regional differences observed ; HIV prevalence in the south was 28.6 % . Among the 78 HIV-infected inmates , 50.7 % were unaware of their HIV status and 44 ( 56.4 % ) had CD4<350 cells/mL , of which only five ( 11 % ) antiretroviral-eligible inmates were receiving it . Nearly half of the participants ( 48.7 % ) reported pre-incarcertion drug injection , primarily of opioids , yet multiple substance use ( 31.6 % ) and alcohol use disorders ( 56.6 % ) were common and 40.3 % met screening criteria for depression . Conclusions This is the only such representative health study of prisoners in the FSU . This study has important implication s for regional prevention and treatment because , unlike elsewhere , there is no recent evidence for reduction in HIV incidence and mortality in the region . The prevalence of infectious diseases and SUDs is high among this sample of prisoners transitioning to the community . It is critical to address pre- and post-release prevention and treatment needs with the development of linkage programs for the continuity of care in the community after release Auricular acupuncture ( AA ) is a widely accepted treatment option for substance abuse that is used in more than 700 treatment centers worldwide . Despite cl aims of perceived clinical benefits by patients and treatment staff , research efforts have failed to substantiate purported benefits , and the mechanism(s ) by which AA serves in the treatment of addiction remain inconclusive . Numerous studies have shown AA to be an effective treatment for perioperative anxiety . In this study , we hypothesize that AA reduces the anxiety associated with withdrawal from psychoactive drugs . The study used a r and omized , controlled design and included a sample of 101 patients recruited from an addiction treatment service . Subjects were assigned to one of three treatment groups ( National Acupuncture Detoxification Association [ NADA ] AA , AA at sham points , or treatment setting control ) and were instructed to attend treatment sessions for 3 days . The primary outcome measure state anxiety was assessed using a pretest-posttest treatment design . The study hypothesis was not confirmed . The NADA protocol was not more effective than sham or treatment setting control in reducing anxiety . The widespread acceptance of AA in the treatment of addiction remains controversial Juvenile offenders with substance use problems are at high risk for deleterious long-term outcomes . This study evaluated the capacity of a promising vocational and employment training program in the building sector ( i.e. , Community Restitution Apprenticeship-Focused Training , CRAFT ) to mitigate such outcomes through enhanced employment and education . Participants were 97 high-risk juvenile offenders ( mean age=15.8 years ) r and omized to CRAFT versus education as usual ( EAU ) intervention conditions . Multi- method procedures measured employment , education , substance use , mental health , and criminal outcomes through a 30-month post-baseline follow-up . CRAFT was significantly more effective than EAU at increasing rates of youth employment and GED attendance . Intervention effects were not observed , however , for months employed , hours worked , or hourly wage . Measures of youth substance use , mental health symptoms , and criminal activity showed no favorable or iatrogenic effects . The potential of CRAFT was modestly supported , and suggestions were made for future research OBJECTIVE The primary purpose of this study was to test a relatively efficient strategy for enhancing the capacity of juvenile drug courts ( JDC ) to reduce youth substance use and criminal behavior by incorporating components of evidence -based treatments into their existing services . METHOD Six JDCs were r and omized to a condition in which therapists were trained to deliver contingency management in combination with family engagement strategies ( CM-FAM ) or to continue their usual services ( US ) . Participants included 104 juvenile offenders ( average age = 15.4 years ; 83 % male ; 57 % White , 40 % African American , 3 % Biracial ) . Eighty-six percent of the youths met criteria for at least 1 substance use disorder , and co-occurring psychiatric diagnoses were highly prevalent . Biological and self-report measures of substance use and self-reported delinquency were assessed from baseline through 9 months postrecruitment . RESULTS CM-FAM was significantly more effective than US at reducing marijuana use , based on urine drug screens , and at reducing both crimes against persons and property offenses . Such favorable outcomes , however , were not observed for the self-report measure of substance use . Although some variation in outcomes was observed between courts , the outcomes were not moderated by demographic characteristics or co-occurring psychiatric disorders . CONCLUSIONS The findings suggest that JDC practice s can be enhanced to improve outcomes for participating juvenile offenders . A vehicle for promoting such enhancements might pertain to the development and implementation of program certification st and ards that support the use of evidence -based interventions by JDCs . Such st and ards have been fundamental to the successful transport of evidence -based treatments of juvenile offenders Background Current research shows that overall numbers for cannabis use among adolescents and young adults dropped in recent years . However , this trend is much less pronounced in continuous cannabis use . With regard to the heightened risk for detrimental health- and development-related outcomes , adolescents and young adults with continuous cannabis use need special attention . The health services structure for adolescents and young adults with substance related problems in Germany , is multifaceted , because different communal , medical and judicial agencies are involved . This results in a rather de central ized organizational structure of the help system . This and further system-inherent characteristics make the threshold for young cannabis users rather high . Because of this , there is a need to establish evidence -based low-threshold help options for young cannabis users , which can be easily disseminated . Therefore , a training programme for young cannabis users ( age 14 - 21 ) was developed in the " CAN Stop " project . Within the project , we seek to implement and evaluate the training programme within different institutions of the help system . The evaluation is sensitive to the different help systems and their specific prerequisites . Moreover , within this study , we also test the practicability of a training provision through laypersons . Methods / Design The CAN Stop study is a four-armed r and omized wait-list controlled trial . The four arms are needed for the different help system setting s , in which the CAN Stop training programme is evaluated : ( a ) the drug addiction aid and youth welfare system , ( b ) the out-patient medical system , ( c ) the in-patient medical system and ( d ) prisons for juvenile offenders . Data are collected at three points , before and after the training or a treatment as usual , and six months after the end of either intervention . Discussion The CAN Stop study is expected to provide an evidence -based programme for young cannabis users seeking to reduce or quit their cannabis use . Moreover , we seek to gain knowledge about the programme 's utility within different setting s of the German help system for young cannabis users and information about the setting s ' specific clientele . The study protocol is discussed with regard to potential difficulties within the different setting s . Trial registration IS RCT N : IS RCT Criminally involved adolescents engage in high levels of risky sexual behavior and alcohol use , and alcohol use may contribute to lack of condom use . Detained adolescents ( n = 484 ) were r and omized to ( 1 ) a theory-based sexual risk reduction intervention ( GPI ) , ( 2 ) the GPI condition with a group-based alcohol risk reduction motivational enhancement therapy component ( GPI + GMET ) , or ( 3 ) an information-only control ( INFO ) . All interventions were presented in same-sex groups in single sessions lasting from 2 to 4 hr . Changes to putative theoretical mediators ( attitudes , perceived norms , self-efficacy , and intentions ) were measured immediately following intervention administration . The primary outcomes were risky sexual behavior and sexual behavior while drinking measured 3 months later ( 65.1 % retention ) . The GPI + GMET intervention demonstrated superiority over both other conditions in influencing theoretical mediators and over the INFO control in reducing risky sexual behavior . Self-efficacy and intentions were significant mediators between condition and later risky sexual behavior . This study contributes to an underst and ing of harm reduction among high-risk adolescents and has implication s for underst and ing circumstances in which the inclusion of GMET components may be effective This paper reports results from the first controlled trial of opioid withdrawal treatment in the UK using lofexidine in a prison setting . Seventy-four opioid dependent male inmates at a Southern Engl and prison were r and omised to receive either methadone ( the st and ard prison treatment ) or lofexidine using a r and omised double-blind design . No significant statistical difference between the treatment groups was found in relation to the primary variable of severity of withdrawal symptoms ( effect size=0.12 ) . No discernible difference was found in the sitting blood pressure or heart rate of the two groups during the trial . These results provide support for the use of lofexidine for the management of opioid detoxification in the prison setting This study tested the viability of auricular acupuncture in prisons for alleviating inmates ' symptoms of psychological and physical discomfort and reducing their drug use . The experimental NADA-Acudetox protocol was compared with a non-specific helix control protocol in a r and omized trial . Over a period of 18 months , a 4-week , 14-session auricular acupuncture treatment program was offered in two prisons to 163 men and women with self-reported drug use . Among treatment completers , no differences by method were found in self-reported symptoms of discomfort . Drug use occurred in the NADA group but not in the helix group . In contrast , confidence in the NADA treatment increased over time while it decreased for the helix treatment . No significant negative side effects were observed for either method . Participants in both groups reported reduced symptoms of discomfort and improved nighttime sleep . Future research should compare auricular acupuncture to a non-invasive control in order to attempt to disentangle active effects from placebo The purpose of this study was to determine whether motivational interviewing ( MI ) , compared with an attention control condition ( relaxation training [ RT ] ) enhances substance abuse treatment engagement in incarcerated adolescents . At the start of incarceration , adolescents were r and omly assigned to individually administered MI or RT . Subsequently , therapists and adolescents ( N = 130 ) rated degree of adolescent participation in the facility 's st and ard care group-based treatments targeting crime and substance use . All adolescents received the facility st and ard care treatment after their individual MI or RT session . MI statistically significantly mitigated negative substance abuse treatment engagement . Other indicators of treatment engagement were in the expected direction ; however , effect sizes were small and nonsignificant . These findings are significant , given concerns regarding the deleterious effects of treating delinquent adolescents in groups and the potential for adolescents to reinforce each other 's negative behavior , which in turn may lead to escalated substance use and other delinquent behaviors after release OBJECTIVES The aim was to determine whether methadone maintenance treatment reduced heroin use , syringe sharing and HIV or hepatitis C incidence among prisoners . METHODS All eligible prisoners seeking drug treatment were r and omised to methadone or a waitlist control group from 1997 to 1998 and followed up after 4 months . Heroin use was measured by hair analysis and self report ; drugs used and injected and syringe sharing were measured by self report . Hepatitis C and HIV incidence was measured by serology . RESULTS Of 593 eligible prisoners , 382 ( 64 % ) were r and omised to MMT ( n=191 ) or control ( n=191 ) . 129 treated and 124 control subjects were followed up at 5 months . Heroin use was significantly lower among treated than control subjects at follow up . Treated subjects reported lower levels of drug injection and syringe sharing at follow up . There was no difference in HIV or hepatitis C incidence . CONCLUSIONS Consideration should be given to the introduction of prison methadone programs particular where community based programs exist BACKGROUND Unemployment is associated with negative outcomes both during and after drug abuse treatment . Interventions design ed to increase rates of employment may also improve drug abuse treatment outcomes . The purpose of this multi-site clinical trial was to evaluate the Job Seekers ' Workshop ( JSW ) , a three session , manualized program design ed to train patients in the skills needed to find and secure a job . METHOD Study participants were recruited through the NIDA Clinical Trials Network ( CTN ) from six psychosocial counseling ( n=327 ) and five methadone maintenance ( n=301 ) drug treatment programs . Participants were r and omly assigned to either st and ard care ( program-specific services plus brochure with local employment re sources ) ( SC ) or st and ard care plus JSW . Three 4-h small group JSW sessions were offered weekly by trained JSW facilitators with ongoing fidelity monitoring . RESULTS JSW and SC participants had similar 12- and 24-week results for the primary outcome measure ( i.e. , obtaining a new taxed job or enrollment in a training program ) . Specifically , one-fifth of participants at 12weeks ( 20.1 - 24.3 % ) and nearly one-third at 24 weeks ( 31.4 - 31.9 % ) had positive outcomes , with " obtaining a new taxed job " accounting for the majority of cases . CONCLUSION JSW group participants did not have higher rates of employment/training than SC controls . Rates of job acquisition were modest for both groups , suggesting more intensive interventions may be needed . Alternate targets ( e.g. , enhancing patient motivation , training in job-specific skills ) warrant further study as well This study reports results from an evaluation of the experimental Rio Hondo driving under the influence ( DUI ) court of Los Angeles County , California . Interviews and official record checks with 284 research participants who were r and omly assigned to a DUI court or a traditional criminal court were assessed at baseline and at 24-month follow-up . The interviews assessed the impact of the DUI court on self-reported drunk driving behavior , the completion of treatment , time spent in jail , alcohol use , and stressful life events . Official record checks assessed the impact of the DUI court on subsequent arrests for driving under the influence and other drinking-related behaviors . Few differences on any outcomes were observed between participants in the experimental DUI court and those assigned to the traditional court . The results suggest that the DUI court model had little additional therapeutic or public safety benefit over the traditional court process . The implication of these findings for the popularity of specialized courts for treating social problems is discussed Individuals who use heroin and illicit opioids are at high risk for infection with human immunodeficiency virus ( HIV ) and other blood-borne pathogens , as well as incarceration . The purpose of the r and omized trial reported here is to compare outcomes between participants who initiated methadone maintenance treatment ( MMT ) prior to release from incarceration , with those who were referred to treatment at the time of release . Participants who initiated MMT prior to release were significantly more likely to enter treatment postrelease ( P < .001 ) and for participants who did enter treatment , those who received MMT prerelease did so within fewer days ( P = .03 ) . They also reported less heroin use ( P = .008 ) , other opiate use ( P = .09 ) , and injection drug use ( P = .06 ) at 6 months . Initiating MMT in the weeks prior to release from incarceration is a feasible and effective way to improve MMT access postrelease and to decrease relapse to opioid use This study compared factors that predict treatment outcomes in men and women r and omly assigned to two therapeutic communities differing primarily in length of inpatient and outpatient treatment . Based on the prior research literature comparing treatment outcomes of men and women , we formulated the following research question : Do factors that predict drug use at follow-up , postdischarge arrest , and employment at follow-up differ for men and women ? Self-reports and objective measures of criminal activity and substance abuse were collected at pre- and posttreatment interviews . Separate regression analyses were conducted for men and women for each of the three outcome variables . The results showed that the predictors of outcome for men and women were similar . Clients who completed the 12-month treatment programs had better outcomes regardless of gender . Men and women who completed treatment were characterized at follow-up by substantial reductions in drug use and arrests and by increased employment . Results further suggested that the longer residential treatment program had a particularly beneficial impact on women . Number of prior arrests was also associated with postdischarge outcomes for women . Women with more arrests at admission were more likely to have a postdischarge arrest and less likely to be employed at follow-up . This finding provides invaluable information about which women may be at greater risk for relapse and in need of additional services . We conclude that completion of treatment is the key predictor of treatment outcomes for both men and women Juvenile drug court ( JDC ) programs have exp and ed rapidly over the past 20 years and are an increasingly popular option for rehabilitating juvenile offenders with substance use problems . Given the high cost of crime to society , an important economic question is whether and to what extent JDC programs reduce criminal activity among juvenile offenders . To address this question , the present study added an economic cost analysis to an ongoing r and omized trial of JDC conducted in Charleston , South Carolina . Four treatment conditions were included in the parent study : Family Court with usual community-based treatment ( FC , the comparison group ) , Drug Court with usual community-based treatment ( DC ) , DC with Multisystemic Therapy ( DC/MST ) , and DC/MST enhanced with Contingency Management ( DC/MST/CM ) . The economic study estimated the cost of criminal activity for nine specific crimes at baseline ( pretreatment ) and 4 and 12 months thereafter . A number of method ological challenges were encountered , suggesting that it may be more difficult to economically quantify frequency and type of criminal activity for adolescents than for adults . The present paper addresses method ological approaches and challenges , and proposes guidelines for future economic evaluations of adolescent substance abuse and crime prevention programs The present report is an intent-to-treat analysis involving secondary data drawn from the first r and omized clinical trial of prison-initiated methadone in the United States . This study examined predictors of treatment entry and completion in prison . A sample of 211 adult male prerelease inmates with preincarceration heroin dependence were r and omly assigned to one of three treatment conditions : counseling only ( counseling in prison ; n = 70 ) ; counseling plus transfer ( counseling in prison with transfer to methadone maintenance treatment upon release ; n = 70 ) ; and counseling plus methadone ( methadone maintenance in prison , continued in a community-based methadone maintenance program upon release ; n = 71 ) . Entered prison treatment ( p < . 01 ) , and completed prison treatment ( p<.001 ) were significantly predicted by the set of 10 explanatory variables and favored the treatment conditions receiving methadone . The present results indicate that individuals who are older in age and have longer prison sentences may have better outcomes than younger individuals with shorter sentences , meaning they are more likely to enter and complete prison-based treatment . Furthermore , implication s for the treatment of prisoners with prior heroin dependence and for conducting clinical trials may indicate the importance of examining individual characteristics and the possibility of the examination of patient preference This study reports results from interviews with 157 research participants who were interviewed 3 years after r and omization into treatment and control conditions in the evaluation of the Baltimore City Drug Treatment Court . The interviews asked about crime , substance use , welfare , employment , education , mental and physical health , and family and social relationships . Program participants reported less crime and substance use than did controls . Few differences between groups were observed on other outcomes , although treatment cases were less likely than controls to be on the welfare rolls at the time of the interview . Effects differed substantially according to the originating court Cognitive-behavioral therapy ( CBT ) , because of its comparatively high level of cognitive dem and , is likely to be challenging for substance users with limitations in cognitive function . However , it is not known whether computer-assisted versions of CBT will be particularly helpful ( e.g. , allowing individualized pace and repetition ) or difficult ( e.g. , via complexity of computerized delivery ) for such patients . In this secondary analysis of data collected from a r and omized clinical trial evaluating computer-assisted CBT , four aspects of cognitive functioning were evaluated among 77 participants . Those with higher levels of risk taking completed fewer sessions and homework assignments and had poorer substance use outcomes AIMS To evaluate physical and mental health and compare treatment outcomes in opiate-dependent patients substituted either with heroin or methadone . DESIGN Twelve-month open-label r and omized controlled trial . SETTING Out-patient substitution clinics in seven German cities . PARTICIPANTS A total of 1015 opiate-dependent individuals . MEASUREMENTS Opiate Treatment Index-Health Scale Score ( OTI ) , Body Mass Index ( BMI ) , serology for infectious diseases such as hepatitis B , C and human immunodeficiency virus as well as tuberculosis , Karnofsky Performance Scale ( KPS ) , electrocardiogram ( ECG ) , echocardiogram , Symptom Checklist 90-R ( SCL-90-R ) , Global Assessment of Functioning ( GAF ) , Modular System for Quality of Life and study medication-related serious adverse events ( SAE ) . FINDINGS Improvements were found in both heroin and methadone substituted patients regarding OTI , BMI , KPS , SCL-90-R , and GAF , but they were more pronounced for the heroin group ( analysis of variance , all P = 0.000 ) . The frequency of pathological echocardiograms decreased in the heroin group and increased in the methadone group ( χ(2 ) test , < 0.05 ) . Markers for infectious diseases and frequencies of pathological ECGs did not differ between baseline and 12 months , or between treatment groups . Study medication-related serious adverse events , all of which were treated successfully , occurred 2.5 times more often in the heroin group . The majority of heroin-related SAEs ( 41 of 58 ) occurred within a few minutes of the injections . CONCLUSIONS The integration of severe injection drug users either in methadone or heroin-assisted maintenance treatment has positive effects on most physical and mental change-sensitive variables , with heroin showing superior results . Due to medication-related adverse events , patients should be observed for 15 minutes after a heroin injection Well-controlled , r and omized studies of correctional interventions examining gender effects are rare . This study examined gender main effects and gender × treatment interactions in a multisite r and omized trial ( N = 431 ) comparing a new form of correctional supervision for drug-involved offenders ( collaborative behavioral management [ CBM ] ) to st and ard parole . Outcomes included repeated measures of yes/no use of primary drug , alcohol use , and recidivism during 9 months postrelease . Generalized estimating equation analyses indicated that despite using harder drugs at baseline , women were less likely than men to use their primary drug and to use alcohol during the follow-up period . No gender-related differences in recidivism were found . Treatment interacted with gender to predict alcohol use , with women in CBM reporting the best alcohol outcomes ( only 5 % of women used alcohol during the follow-up period ) . The clear expectations , positive reinforcement , recognition of successes , fairness , and support present in CBM may be particularly important for women parolees Young marijuana abusers rarely seek treatment themselves and are difficult to engage in treatment when referred by social agencies . To evaluate treatment engagement strategies in this population , 65 young probation-referred marijuana abusers were r and omly assigned to either three-session motivational enhancement therapy ( MET alone ) or three-session MET plus contingency management ( MET/CM ) , with vouchers for treatment attendance . A significantly higher number of participants in the MET/CM condition completed the three-session intervention as compared with MET alone . Participants in both conditions reported significant reductions in marijuana use and improvement in legal problems . These findings suggest that young marijuana abusers benefit from scientifically vali date d treatments AIM The aim of this study is to define the efficacy of dihydrocodeine as an alternative to methadone in the maintenance treatment of opiate dependence . DESIGN A pragmatic open-label r and omized controlled study of patients recommended for opiate maintenance treatment to test equivalence of the two treatment options with follow-up continuing for up to 42 months after recruitment . SETTING Assessment at either Edinburgh 's Community Drug Problem Service or at two general practitioner practice s with specialist drug community psychiatric nurses , then with shared care follow-up . PARTICIPANTS Two hundred and thirty-five subjects ( 168 male , 67 female ) with opiate dependence syndrome were recruited . Subjects selected were suitable for opiate maintenance treatment . Routine treatment was offered throughout . INTERVENTION Patients were r and omized to receive either methadone mixture 1 mg/ml or dihydrocodeine , 30 mg or 60 mg tablets . MEASUREMENTS The primary outcome measure was retention in treatment . Eight secondary outcomes included total illicit opiate use , reported crime , physical health , mental health , injecting drug use , overdoses , selling drugs and being in education or work . Measures were compared over 42 months follow-up . FINDINGS There was no difference in groups for retention in treatment at follow-up and there was improvement in all secondary outcomes from baseline . No significant difference in outcomes was found between r and omized groups over time . Compliance with r and omized treatment differed by r and omized group and was affected by experiences in custody during follow-up . Those r and omized to dihydrocodeine were more likely to switch treatments . CONCLUSIONS These results , combined with existing clinical experience , provide evidence that dihydrocodeine is a viable alternative to methadone as a maintenance treatment for opiate dependence . Indirect comparisons with other studies show dihydrocodeine ( and methadone ) to be superior to placebo An initial efficacy test of an innovative behavioral outpatient treatment model for adolescents with problematic use of marijuana enrolled 69 adolescents , aged 14 - 18 , and r and omly assigned them to one of two treatment conditions . Both conditions received individualized Motivational Enhancement and Cognitive Behavioral Therapy ( MET/CBT ) and a twice-weekly drug-testing program . The experimental contingency management condition involved a clinic-delivered , abstinence-based incentive program , and weekly behavioral parent training sessions that included a parent-delivered , abstinence-based , substance monitoring contract . The comparison condition included an attendance-based incentive program , and weekly psychoeducational parent sessions . Follow-up assessment s were performed at 3 , 6 , and 9 months post-treatment . The experimental condition showed greater marijuana abstinence during treatment , e.g. , 7.6 vs. 5.1 continuous weeks and 50 % vs. 18 % achieved > or = 10 weeks of abstinence . Improvements were found in parenting and youth psychopathology across treatment conditions , and improvements in negative parenting uniquely predicted post-treatment abstinence . The outcomes observed in the experimental condition are consistent with adult substance-dependence treatment literature , and suggest that integrating CM abstinence-based approaches with other empirically based outpatient interventions provides an alternative and efficacious treatment model for adolescent substance abuse/dependence . Replication and continued development of more potent interventions remain needed to further advance the development of effective substance abuse treatments for adolescents Objective To assess the impact of a positive behavioral reinforcement intervention on psychosocial functioning of inmates over the course of treatment and on post-treatment self-reported measures of treatment participation , progress , and satisfaction . Method Male ( n = 187 ) and female ( n = 143 ) inmates participating in 12-week prison-based intensive outpatient ( IOP ) drug treatment were r and omly assigned to receive st and ard treatment ( ST ) or st and ard treatment plus positive behavioral reinforcement ( BR ) for engaging in targeted activities and behaviors . Participants were assessed for psychosocial functioning at baseline and at the conclusion of treatment ( post-treatment ) . Self-reported measures of treatment participation , treatment progress , and treatment satisfaction were also captured at post-treatment . Results The intervention affected female and male subjects differently and not always in a way that favored BR subjects , as compared to the ST subjects , most notably on measures of depression and criminal thinking . Conclusions Possible explanations for the results include differences in the male and female custody environments combined with the procedures that study participants had to follow to earn and /or receive positive reinforcement at the two study sites , as well as baseline differences between the genders and a possible floor effect among females on measures of criminality . Limitations of the study included the inability to make study participants blind to the study conditions and the possible over-br and ing of the study , which may have influenced the results OBJECTIVE This secondary analysis of data from a r and omized controlled trial tested two behavioral economics mechanisms ( substitutability and delay discounting ) to explain outcomes using contingency management ( CM ) for methamphetamine dependence . Frequency and purchase type ( hedonic/utilitarian and consumable/durable ) of CM payments were also examined . METHODS A total of 82 methamphetamine-dependent gay/bisexual men r and omly assigned to conditions delivering CM received monetary vouchers in exchange for stimulant-negative urine sample s in a 16-week trial requiring thrice weekly visits ( Shoptaw et al. , 2005 ) . At any visit participants could redeem vouchers for goods . A time-lagged counting process Cox Proportional Hazards model for recurrent event survival analysis examined aspects of the frequency and type of these CM purchases . RESULTS After controlling for severity of baseline methamphetamine use and accumulated CM wealth , as measured by cumulative successful earning days , participants who redeemed CM earnings at any visit ( " spenders " ) were significantly more likely to produce stimulant-negative urine sample s in the subsequent visit , compared with those who did not redeem ( " savers " ) 1.011 * [ 1.005 , 1.017 ] , Z = 3.43 , p < .001 . CONCLUSIONS Findings support the economic concept of substitutability of CM purchases and explain trial outcomes as a function of frequency of CM purchases rather than frequency or accumulated total CM earnings . Promotion of frequent purchases in incentive-based programs should facilitate substitution for the perceived value of methamphetamine and improve abstinence outcomes Abstract Methadone and buprenorphine are both efficacious treatments for opioid dependency , but they also have different pharmacological properties and clinical delivery methods that can affect their acceptability to patients . This study was intended to increase our knowledge of heroin-dependent individuals ' perceptions of methadone vs. buprenorphine maintenance based on actual experiences with each . The study sample consists of heroin-dependent men at the Rikers Isl and jail in New York City who were voluntarily r and omly assigned to methadone or buprenorphine maintenance in jail . Methadone patients were more likely to report feeling uncomfortable the first few days , having side/withdrawal effects during treatment , and being concerned about continued dependency on medication after release . In contrast , buprenorphine patients ' main issue was the bitter taste . All of the buprenorphine patients stated that they would recommend the medication to others , with almost all preferring it to methadone . Ninety-three percent of buprenorphine vs. 44 % of methadone patients intended to enroll in those respective treatments after release , with an added one-quarter of the methadone patients intending to enroll in buprenorphine instead . These results reinforce the importance of increasing access to buprenorphine treatment in the community for indigent heroin-dependent offenders A sample of 296 drug-using inmates in 14 Swedish prisons was r and omized during 2004–2006 into three intervention groups ; Motivational Interviewing delivered by counselors with workshop-only training , or by counselors with workshop training followed by peer group supervision , and controls . Drug and alcohol use was measured by the Addiction Severity Index ( ASI ) at intake and at 10 months after release . Complete data from 114 clients were analyzed by a stepwise regression analysis . All three groups reduced alcohol and drug use . Limitations in the study are discussed and future research is suggested . The study is financed by grants from the Research Committee of the National Prison and Probation Administration OBJECTIVE A strong relation between negative affect and craving has been demonstrated in laboratory and clinical studies , with depressive symptomatology showing particularly strong links to craving and substance abuse relapse . Mindfulness-based relapse prevention ( MBRP ) , shown to be efficacious for reduction of substance use , uses mindfulness-based practice s to teach alternative responses to emotional discomfort and lessen the conditioned response of craving in the presence of depressive symptoms . The goal in the current study was to examine the relation between measures of depressive symptoms , craving , and substance use following MBRP . METHOD Individuals with substance use disorders ( N = 168 ; mean age 40.45 years , SD = 10.28 ; 36.3 % female ; 46.4 % non-White ) were recruited after intensive stabilization , then r and omly assigned to either 8 weekly sessions of MBRP or a treatment-as-usual control group . Approximately 73 % of the sample was retained at the final 4-month follow-up assessment . RESULTS Results confirmed a moderated-mediation effect , whereby craving mediated the relation between depressive symptoms ( Beck Depression Inventory ) and substance use ( Timeline Follow-Back ) among the treatment-as-usual group but not among MBRP participants . MBRP attenuated the relation between postintervention depressive symptoms and craving ( Penn Alcohol Craving Scale ) 2 months following the intervention ( f(2 ) = .21 ) . This moderation effect predicted substance use 4 months following the intervention ( f(2 ) = .18 ) . CONCLUSION MBRP appears to influence cognitive and behavioral responses to depressive symptoms , partially explaining reductions in postintervention substance use among the MBRP group . Although results are preliminary , the current study provides evidence for the value of incorporating mindfulness practice into substance abuse treatment and identifies a potential mechanism of change following MBRP Background Behaviors associated with opioid dependence often involve criminal activity , which can lead to incarceration . The impact of a history of incarceration on outcomes in primary care office-based buprenorphine/naloxone is not known . Objective The purpose of this study is to determine whether having a history of incarceration affects response to primary care office-based buprenorphine/naloxone treatment . Design In this post hoc secondary analysis of a r and omized clinical trial , we compared demographic , clinical characteristics , and treatment outcomes among 166 participants receiving primary care office-based buprenorphine/naloxone treatment stratifying on history of incarceration . Main Results Participants with a history of incarceration have similar treatment outcomes with primary care office-based buprenorphine/naloxone than those without a history of incarceration ( consecutive weeks of opioid-negative urine sample s , 6.2 vs. 5.9 , p = 0.43 ; treatment retention , 38 % vs. 46 % , p = 0.28 ) . Conclusions Prior history of incarceration does not appear to impact primary care office-based treatment of opioid dependence with buprenorphine/naloxone . Community health care providers can be reassured that initiating buprenorphine/naloxone in opioid dependent individuals with a history of incarceration will have similar outcomes as those without this history AIMS Methadone maintenance treatment has been made available in China in response to the rapid spread of human immunodeficiency virus ( HIV ) , but high rates of dropout and relapse are problematic . The aim of this study was to apply and test if a contingency management ( or motivational incentives ) intervention can improve treatment retention and reduce drug use . DESIGN R and om assignment to usual care with ( n = 160 ) or without ( n = 159 ) incentives during a 12-week trial . Incentives participants earned draws for a chance to win prizes on two separate tracks targeting opiate-negative urine sample or consecutive attendance ; the number of draws increased with continuous abstinence or attendance . SETTING Community-based methadone maintenance clinics in Shanghai and Kunming . PARTICIPANTS The sample was 23.8 % female , mean age was 38 , mean years of drug use was 9.4 and 57.8 % had injected drugs in the past 30 days . MEASUREMENTS Treatment retention and negative drug urine . FINDINGS Relative to the treatment-as-usual ( control ) group , better retention was observed among the incentive group in Kunming ( 75 % versus 44 % ) , but no difference was found in Shanghai ( 90 % versus 86 % ) . Su bmi ssion of negative urine sample s was more common among the incentive group than the usual care ( 74 % versus 68 % in Shanghai , 27 % versus 18 % in Kunming ) , as was the longest duration of sustained abstinence ( 7.7 weeks versus 6.5 in Shanghai , 2.5 versus 1.6 in Kunming ) . The average total prize amount was 371 Yuan ( or $ 55 ) per participant ( 527 for Shanghai versus 216 in Kunming ) . CONCLUSIONS Contingency management improves treatment retention and drug abstinence in methadone maintenance treatment clinics in China , although there can be considerable site differences in magnitude of effects ABSTRACT Evaluated impact of motivational enhancement ( ME ) of substance abuse treatment compared to relaxation training ( RT ) on sex without condoms ( overall and involving substance use ) 3 months following release among incarcerated adolescents . This r and omized clinical trial involved 114 incarcerated adolescents from the Northeast . Regression analyses determined if treatment condition , baseline levels of depressive symptoms , and their interaction predicted condom non-use 3 months post-release , controlling for baseline condom non-use . Among those who reported fewer baseline depressive symptoms , those in ME condition reported significantly less condom non-use , in general and involving marijuana use compared with those in RT condition . Periods of incarceration represent opportunities to help juvenile detainees reduce behaviors that impact their health and the health of those with whom they interact in the Community Purpose To examine the effect of online counseling abuse counseling on drug use among underserved patients . Methods Subjects were recruited from an Indian Reservation in Eagle Butte , South Dakota ; a family court in Newark , New Jersey ; a probation office in Alex and ria , Virginia ; and a co-occurring disorders treatment clinic in Washington , District of Columbia . Subjects were predominantly poor , undereducated , unemployed , court involved , or diagnosed with co-occurring psychiatric disorders . A total of 79 subjects volunteered to participate in the project . Subjects were r and omly assigned to either a control group or an experimental group . The control and experimental groups were both issued an Internet-ready computer and 1 year of Internet service . Only the experimental group had access to online counseling intervention . Drug use was measured using a combination of self-usage reporting and supervised urine tests . Results Urine tests were available for 37 % of subjects . Exit surveys containing self-reported usage were obtained from 54 % of the subjects . Self-usage reports or urine test results were available from 70 % of subjects . The difference of the rates of drug use in the control and experimental groups ( as calculated from urine tests or through self-report ) was not significantly different from zero , suggesting that online counseling had not led to a reduction in substance use . It is possible that the study lacked sufficient power to detect small differences in the rate of drug use in the experimental and control groups . Conclusions Additional research is needed to establish the efficacy of online counseling in hard-to-reach population The effectiveness and transportability of multisystemic therapy ( MST ) were examined in a study that included 118 juvenile offenders meeting DSM-III-R criteria for substance abuse or dependence and their families . Participants were r and omly assigned to receive MST versus usual community services . Outcome measures assessed drug use , criminal activity , and days in out-of-home placement at posttreatment ( T2 ) and at a 6-month posttreatment follow-up ( T3 ) ; also treatment adherence was examined from multiple perspectives ( i.e. , caregiver , youth , and therapist ) . MST reduced alcohol , marijuana , and other drug use at T2 and total days in out-of-home placement by 50 % at T3 . Reductions in criminal activity , however , were not as large as have been obtained previously for MST . Examination of treatment adherence measures suggests that the modest results of MST were due , at least in part , to difficulty in transporting this complex treatment model from the direct control of its developers . Increased emphasis on quality assurance mechanisms to enhance treatment fidelity may help overcome barriers to transportability Background : After prison release , offenders with heroin use problems are at high risk of relapse and overdose death . There is a particular need for treatments that can be initiated in prison and continued after release into the community . Methadone maintenance treatment has been shown to reduce heroin use , criminality and mortality . Naltrexone implant treatment has not previously been evaluated in prison setting s. Methods : This study compares the effects of naltrexone implants and methadone treatment on heroin and other illicit drug use , and criminality among heroin-dependent inmates after release from prison . Results : Forty-six volunteers were r and omly allocated to naltrexone implants or methadone before release . Intention-to-treat analyses showed reductions in both groups in frequency of use of heroin and benzodiazepines , as well as criminality , 6 months after prison release . Conclusions : Naltrexone implants may be a valuable treatment option in prison setting Objective : To preliminarily evaluate telephone-delivered motivational enhancement therapy ( MET ) in motivating unadjudicated and nontreatment seeking intimate partner violence ( IPV ) perpetrators , who also use substances , to self-refer into treatment . Method : 124 adult men were recruited via a multimedia marketing campaign and were r and omly assigned to the intervention ( MET ) or comparison group following a baseline assessment . Participants in the MET condition received a personalized feedback report on their IPV and substance-use behaviors , consequences , and social norms beliefs . Results : Results supported the likely effectiveness of MET in short-term reduction of IPV behavior , increasing motivation for treatment seeking , and changing perceived norms for IPV and substance abuse ( SA ) . Conclusions : Applications for brief MET interventions to facilitate voluntary treatment entry among substance-using IPV perpetrators are discussed Target population s have always been a thorny issue for correctional programs . In this experiment of seamless treatment for probationers in two sites , offenders were r and omly assigned to the seamless model ( drug treatment incorporated into probation supervision ) or traditional referral model to services in the community . The experiment blocked on risk level to measure the differential effects on rearrest and substance abuse . The seamless system model improved treatment participation with greater gains for the offenders who were high risk in both sites . Yet no main effects were observed on drug use or rearrest , although effect sizes illustrate that small effects can be observed for the offenders who are high risk . Part of the failure to observe main effects is because of instrumentation problems , namely , that most substance abusers in the experiment had low-severity substance abuse problems and were marijuana users . The focus on sound dynamic factors may assist with identifying the appropriate target population s for correctional interventions Abstract Background : Employment has been identified as an important part of substance abuse treatment and is a predictor of treatment retention , treatment completion , and decreased relapse . Although employment interventions have been design ed for substance abusers , few interventions have focused specifically on drug-involved offenders . Objectives : The purpose of this study was to examine employment outcomes for drug-involved offenders who received a tailored employment intervention . Methods : In a r and omized controlled trial , baseline and follow-up data were collected from 500 drug-involved offenders who were enrolled in a drug court program . Participants were r and omly assigned to drug court as usual ( control group ) or to the employment intervention in addition to drug court . Results : Intent-to-treat analyses found that the tailored intervention was associated only with more days of paid employment at follow-up ( 210.1 vs. 199.9 days ) . When focusing on those with greater employment assistance needs , a work trajectory analyses , which took into account participants ’ pre-baseline employment pattern ( negative or positive ) , revealed that intervention group participants had higher rates of employment ( 82.1 % vs. 64.1 % ) , more days paid for employment ( 188.9 vs. 157.0 days ) , and more employment income ( $ 8623 vs. $ 6888 ) at follow-up than control group participants . Conclusion : The present study adds to the growing substance abuse and employment literature . It demonstrates the efficacy of an innovative employment intervention tailored for drug-involved offenders by showing positive changes in 12-month employment outcomes , most strongly for those who have not had recent employment success The study r and omly assigned male inmates with co-occurring serious mental illness and chemical abuse ( MICA ) disorders to either modified therapeutic community ( MTC ) or mental health ( MH ) treatment programs . On their release from prison , MICA inmates who completed the prison MTC program could enter the MTC aftercare program . The results , obtained from an intent-to-treat analysis of all study entries , showed that inmates r and omized into the MTC group had significantly lower rates of reincarceration compared with those in the MH group . The results also show that differences between the MTC + aftercare and comparison group across a variety of crime outcomes ( i.e. any criminal activity , and alcohol or drug related criminal activity ) are consistent and significant , and persist after an examination of various threats to validity ( e.g. initial motivation , duration of treatment , exposure to risk ) . This study provides some support for the effectiveness of the prison TC only condition . The findings are encouraging and consonant with other studies of integrated prison and aftercare TC programs for substance abusing non-MICA offenders , although qualified by the possibility that selection bias ( i.e. differences in motivation on entry into aftercare ) may be operating . Nevertheless , given the available evidence and the need for effective programming for MICA offenders , program and policy makers should strongly consider developing integrated prison and aftercare modified TC programs for MICA offenders The primary focus of the current study is to examine whether gender and other baseline characteristics were significantly associated with more severe patterns of drug use . It involves data from 260 male and female prerelease prison inmates with preincarceration heroin dependence who enrolled in a r and omized clinical trial of prison-initiated buprenorphine . Three outcomes are examined : ( a ) lifetime intravenous drug use , ( b ) lifetime number of drugs used , and ( c ) heroin use in prison . Regarding lifetime intravenous drug use ; race ( p < .001 ) , education ( p < .009 ) , age ( p < .001 ) , and psychological treatment ( p = .028 ) were significant . Concerning lifetime number of drugs used ; race ( p < .001 ) and age of first crime ( p = .001 ) were significant . Finally , gender ( p = .004 ) , was the only significant variable in terms of using heroin while in prison . All of these differences may have important clinical , treatment , and research implication s , which are discussed This study assessed a 26-week voucher-based intervention to reinforce abstinence and participation in treatment-related activities among substance-abusing offenders court referred to outpatient treatment under drug diversion legislation ( California ’s Substance Abuse and Crime Prevention Act ) . St and ard treatment consisted of criminal justice supervision and an evidence -based model for treating stimulant abuse . Participants were r and omly assigned to four groups , st and ard treatment ( ST ) only , ST plus vouchers for testing negative , ST plus vouchers for performing treatment plan activities , and ST plus vouchers for testing negative and /or performing treatment plan activities . Results indicate that voucher-based reinforcement of negative urines and of treatment plan tasks ( using a flat reinforcement schedule ) showed no statistically significant effects on measures of retention or drug use relative to the st and ard treatment protocol . It is likely that punishment and reinforcement operating within the criminal justice context had a stronger impact on participants ’ treatment retention and drug use than the relatively low-value vouchers awarded as part of the treatment protocol A study was made of the effectiveness of an aftercare program operating in conjunction with area outpatient drug free treatment programs while organizationally independent of those programs . Parolees and probationers m and ated to treatment were assigned to aftercare on the basis of residence in the catchment areas in which aftercare facilities were located ( n = 32 ) and r and omly to aftercare ( n = 62 ) and control ( n = 51 ) when not a resident in a catchment area . No outcome differences were found between aftercare groups based on proximity to facility . At 6 months postbaseline the combined aftercare group showed significantly lower levels of criminal activity and frequent drug use as compared to controls . At 12 months postbaseline there was an attenuation of group differences with only tendencies toward significance obtained for lower levels of frequent drug use by the aftercare group . The findings are discussed in terms of the relevance of community variables for programming and for underst and ing long-term treatment outcomes Buprenorphine has rarely been administered as an opioid agonist maintenance therapy in a correctional setting . This study introduced buprenorphine maintenance in a large urban jail , Rikers Isl and in New York City . Heroin-dependent men not enrolled in community methadone treatment and sentenced to 10 - 90 days in jail ( N=116 ) were voluntarily r and omly assigned either to buprenorphine or methadone maintenance , the latter being the st and ard of care for eligible inmates at Rikers . Buprenorphine and methadone maintenance completion rates in jail were equally high , but the buprenorphine group reported for their design ated post-release treatment in the community significantly more often than did the methadone group ( 48 % vs. 14 % , p<.001 ) . Consistent with this result , prior to release from Rikers , buprenorphine patients stated an intention to continue treatment after release more often than did methadone patients ( 93 % vs. 44 % , p<.001 ) . Buprenorphine patients were also less likely than methadone patients to withdraw voluntarily from medication while in jail ( 3 % vs. 16 % , p<.05 ) . There were no post-release differences between the buprenorphine and methadone groups in self-reported relapse to illicit opioid use , self-reported re-arrests , self-reported severity of crime or re-incarceration in jail . After initiating opioid agonist treatment in jail , continuing buprenorphine maintenance in the community appears to be more acceptable to offenders than continuing methadone maintenance The purpose of this study was to determine the impact of an intervention seeking to reduce risk for HIV/AIDS infection among a sample of soon-to-be-released adult male inmates . This analysis is based on a r and om sample of 116 adult male prisoners recruited and interviewed prior to their participation in an HIV/AIDS and recidivism risk reduction intervention and again three months after they were reintegrated into the community . The intervention program was design ed to reduce risky sexual behaviors and alcohol , tobacco , and other drug-related behaviors . It had a r and omized , Latin-square design to evaluate adult male offenders across four conditions . Findings indicate that the intervention for the inmate population was effective in reducing sexual self-expectation and substance use and increasing condom use self-efficacy over a three-month period This study examined the efficacy of a Mental Health Treatment Court ( MHTC ) with diversion to treatment supported by an assertive community treatment ( ACT ) model of case management . A total of 235 participants were r and omly assigned to either MHTC or treatment as usual ( TAU ) and assessed over a 2 year period . It was hypothesized that participants in the MHTC would decrease their criminal activity and improve their psychosocial functioning relative to participants receiving TAU . While there were offenders for whom neither treatment was effective , a majority in both groups decreased jail days and improved psychosocial functioning , with MHTC participants demonstrating greater gains in most areas . The impact of implementing the MHTC on community practice s , and the value of integrating criminal justice and mental health systems , is discussed Although drug and alcohol treatment are common requirements in the U.S. criminal justice system , only a minority of clients actually initiate treatment . This paper describes a two-session , web-based intervention to increase motivation for substance abuse treatment among clients using illicit substances . MAPIT ( Motivational Assessment Program to Initiate Treatment ) integrates the extended parallel process model , motivational interviewing , and social cognitive theory . The first session ( completed near the start of probation ) targets motivation to complete probation , to make changes in substance use ( including treatment initiation ) , and to obtain HIV testing and care . The second session ( completed approximately 30days after session 1 ) focuses on goal setting , coping strategies , and social support . Both sessions can generate emails or mobile texts to remind clients of their goals . MAPIT uses theory-based algorithms and a text-to-speech engine to deliver custom feedback and suggestions . In an initial test , participants indicated that the program was respectful , easy to use , and would be helpful in making changes in substance use . MAPIT is being tested in a r and omized trial in two large U.S. probation agencies . MAPIT addresses the difficulties of many probation agencies to maximize client involvement in treatment , in a way that is cost effective and compatible with the existing service delivery system Offenders with a history of opioid dependence are a particularly difficult group to treat . A large proportion of offenders typically relapse shortly after release from prison , commit drug-related crimes , and then are arrested and eventually re-incarcerated . Previous research demonstrated that oral naltrexone was effective in reducing opioid use and preventing recidivism among offenders under federal supervision . The 111 opioid-dependent offenders in this study were under various levels of supervision that included county and federal probation/parole , a treatment court , an alternative disposition program , and an intermediate punishment program . Subjects were r and omly assigned to receive 6 months of either 300 mg per week of oral naltrexone plus st and ard psychosocial treatment as usual ( n = 56 ) or st and ard psychosocial treatment as usual ( TAU ) without naltrexone ( n = 55 ) . While the TAU subjects who remained in treatment used more opioids than the naltrexone subjects who remained , the high dropout rate for both groups made it difficult to assess the effectiveness of naltrexone . The study provides limited support for the use of oral naltrexone for offenders who are not closely monitored by the criminal justice system OBJECTIVE This study compared the effectiveness of two interventions in reducing alcohol use , drug use , and criminal justice charges for persons with severe mental illnesses : first , a community-oriented group intervention with citizenship training and peer support that was combined with st and ard clinical treatment , including jail diversion services , and second , st and ard clinical treatment with jail diversion services alone . METHODS A total of 114 adults with serious mental illness participated in a 2 x 3 prospect i ve longitudinal , r and omized clinical trial with two levels of intervention ( group and peer support for the experimental condition and st and ard services for the control ) and three interviews ( baseline , six months , and 12 months ) . Self-report question naires assessed alcohol and drug use , and program data bases assessed criminal justice contacts . The authors used a mixed-models analysis to assess alcohol and drug use , repeated- measures analysis of covariance to assess criminal justice charges , and correlational analyses to assess the relation between intervention participation and outcome variables . RESULTS The experimental group showed significantly reduced alcohol use in comparison with the control group . Further , results showed a significant group-by-time interaction , where alcohol use decreased over time in the experimental group and increased in the control group . Drug use and criminal justice charges decreased significantly across assessment periods in both groups . CONCLUSIONS Of the outcomes , only decreased alcohol use was attributable to the experimental intervention . Although this may be a chance finding , peer- and community-oriented group support and learning may facilitate decreased alcohol use over time Objective : This secondary data analysis examined the association between criminal justice ( CJ ) status and outcomes over 12 months of methadone maintenance treatment . Methods : In the parent study , 230 newly admitted patients were r and omly assigned to methadone either with or without counseling for 4 months followed by st and ard methadone with counseling . Participants completed the ASI and urine drug testing at baseline and 4- and 12-month follow-up and the Treatment Readiness ( TR ) scale at baseline . The relationship between baseline CJ status ( whether participants were on probation or parole ) , CJ status by study counseling condition , and CJ status by TR with heroin and cocaine use , illegal activity , days in treatment and treatment retention , arrests , and the number of days incarcerated or hospitalized during follow-up was examined . Results : Compared with participants not on probation/parole , probationers/parolees showed significant reductions in cocaine-positive tests from baseline to 12 months ( P < 0.001 ) . Probationers/parolees additionally reported significantly fewer days of illegal activity than nonprobationers/parolees at 12 months ( P = 0.02 ) . There was no relationship between CJ status and counseling condition for any outcomes . The relationship between CJ status and TR was significant only for cocaine-positive tests assessed over time ( P = 0.017 ) . Conclusions : Findings suggest that methadone participants on probation/parole showed improvements in outcomes in comparison with participants not on probation/parole , regardless of whether they received counseling during the first 4 months of treatment This study examined the impact of prison-initiated methadone maintenance at 12 months postrelease . Males with pre-incarceration heroin dependence ( N = 204 ) were r and omly assigned to ( a ) Counseling Only : counseling in prison , with passive referral to treatment upon release ; ( b ) Counseling + Transfer : counseling in prison with transfer to methadone maintenance treatment upon release ; and ( c ) Counseling + Methadone : counseling and methadone maintenance in prison , continued in the community upon release . The mean number of days in community-based drug abuse treatment were , respectively , Counseling Only , 23.1 ; Counseling + Transfer , 91.3 ; and Counseling + Methadone , 166.0 ( p < .01 ) ; all pairwise comparisons were statistically significant ( all ps < .01 ) . Counseling + Methadone participants were also significantly less likely than participants in each of the other two groups to be opioid-positive or cocaine-positive according to urine drug testing . These results support the effectiveness of prison-initiated methadone for males in the United States . Further study is required to confirm the findings for women Abstract The potential motivation of criminal addicts for methadone treatment was tested in the New York City Correctional Institute for Men . Of 165 inmates seen , all with records of five or more jail sentences , 116 ( 70 per cent ) applied for treatment after a single interview . None of them had previously made application to the methadone program . Of 18 r and omly selected from all applicants with release date s between January 1 and April 30 , 1968 , 12 were started on methadone before they left jail and then referred to the program for aftercare . None of them became readdicted to heroin , and nine of 12 had no further convictions during the 50 weeks of follow-up study . All of an untreated control group became readdicted after release from jail , and 15 of 16 were convicted of new crimes during the same follow-up period OBJECTIVES This r and omized controlled study compared acceptance and commitment therapy ( ACT ) , cognitive-behavioral therapy ( CBT ) , and a control group . METHOD The participants were 50 incarcerated women diagnosed with current substance use disorder . Two psychologists carried out pre- and posttreatment assessment and a 6-month follow-up assessment using the following instruments : Anxiety Sensitivity Index , Addiction Severity Index-6 , Mini International Neuropsychiatric Interview , and Acceptance and Action Question naire . RESULTS The study shows that the women who received treatment benefited differentially from the interventions . At posttreatment , CBT was more effective than ACT in reducing anxiety sensitivity ; however , at follow-up , ACT was more effective than CBT in reducing drug use ( 43.8 vs. 26.7 % , respectively ) and improving mental health ( 26.4 % vs. 19.4 % , respectively ) . CONCLUSION ACT may be an alternative to CBT for treatment of drug abuse and associated mental disorders . In fact , at long-term , ACT may be more appropriate than CBT for incarcerated women who present serious problems Marijuana-dependent young adults ( N = 136 ) , all referred by the criminal justice system , were r and omized to 1 of 4 treatment conditions : a motivational/skills-building intervention ( motivational enhancement therapy/cognitive-behavioral therapy ; MET/CBT ) plus incentives contingent on session attendance or su bmi ssion of marijuana-free urine specimens ( contingency management ; CM ) , MET/CBT without CM , individual drug counseling ( DC ) plus CM , and DC without CM . There was a significant main effect of CM on treatment retention and marijuana-free urine specimens . Moreover , the combination of MET/CBT plus CM was significantly more effective than MET/CBT without CM or DC plus CM , which were in turn more effective than DC without CM for treatment attendance and percentage of marijuana-free urine specimens . Participants assigned to MET/CBT continued to reduce the frequency of their marijuana use through a 6-month follow-up The aim of this study was to evaluate the efficacy of a theory-based intervention to increase the use of a new syringe for each injection among injection drug users ( IDUs ) . Users of two needle exchange programs ( NEPs ) were involved . At both sites , participants were assigned at r and om to either the experimental or the control group . Once a week for four weeks , users reported to the NEPs where they logged onto a computer and received an audiovisual message . A total of 260 IDUs were recruited . At baseline , 52.3 % of participants reported that they had not always used new syringes in the previous week . The results indicate that it is possible for IDUs to adopt safer injection practice s. One month after the intervention began , participants in the experimental group were using fewer dirty syringes compared to the control group ( RR : 0.47 CI95 % 0.28–0.79 ; P = .004 ) . This short-term effect was no longer present 3 months later BACKGROUND Primary care opioid substitution treatment ( OST ) has not been compared to program-based OST for community-supervised offenders . OBJECTIVE The purpose of this project was to compare primary care to specialist supervised OST for opioid dependent offenders in terms of substance use and HIV risk outcomes . METHODS This project r and omly assigned 15 jail diversion participants to either : ( i ) primary care buprenorphine OST , ( ii ) specialist facility buprenorphine OST , or ( iii ) specialist facility methadone OST . Participation lasted 13.5 months ( 12-month active treatment plus a post-participation visit ) . RESULTS All subjects endorsed 0 days of opioid use in the previous 14 at follow-up . Specialty care reduced HIV risk ( Risk Assessment Battery composite score ) over 6 months ( -.24 ± .17 ) compared to primary care ( .02 ± .14 ; p = .032 ) . CONCLUSION Findings support primary care OST feasibility for a community-supervised offender sample . Specialist care may facilitate improvements in secondary outcomes , such as HIV risk behaviors . SCIENTIFIC SIGNIFICANCE Further research is needed to clarify ( i ) the role of primary care in addicted offender management , and ( ii ) the matching of offenders , based upon history and co-morbidity , to care coordination conditions Waiting time is a contemporary reality of many drug abuse treatment programs , result ing in substantial problems for substance users and society . Individual and system factors that influence waiting time are diverse and may vary at different points in the treatment continuum . This study assessed waiting time preceding clinical assessment at a central ized intake unit and during the period after the assessment but before treatment entry . The present study included 577 substance abusers who were enrolled in a large clinical trial of two brief treatment interventions in a midsize metropolitan area in Ohio . Bivariate analyses identified individual and system factors that influenced pre assessment and post assessment waiting time , as well as total wait to treatment services . Multivariate analyses demonstrated that longer wait time for an assessment is influenced by being court referred , less belief in having a substance abuse problem , and less desire for change . A shorter wait to actually enter treatment is predicted by having a case manager , being more ready for treatment , and having less severe employment and alcohol problems . The different influences present during the two waiting periods suggest that assessment and treatment programs need to implement system changes and entry enhancement interventions that are specific to the needs of substance abusers at each waiting period AIMS This study examined the effectiveness of methadone maintenance initiated prior to or just after release from prison at 6 months post-release . DESIGN A three-group r and omized controlled trial was conducted between September 2003 and June 2005 . SETTING A Baltimore pre-release prison . PARTICIPANTS Two hundred and eleven adult pre-release inmates who were heroin-dependent during the year prior to incarceration . INTERVENTION Participants were assigned r and omly to the following : counseling only : counseling in prison , with passive referral to treatment upon release ( n = 70 ) ; counseling + transfer : counseling in prison with transfer to methadone maintenance treatment upon release ( n = 70 ) ; and counseling + methadone : methadone maintenance and counseling in prison , continued in a community-based methadone maintenance program upon release ( n = 71 ) . MEASUREMENTS Addiction Severity Index at study entry and follow-up . Additional assessment s at 6 months post-release were treatment record review ; urine drug testing for opioids , cocaine and other illicit drugs . FINDINGS Counseling + methadone participants were significantly more likely than both counseling only and counseling + transfer participants to be retained in drug abuse treatment ( P = 0.0001 ) and significantly less likely to have an opioid-positive urine specimen compared to counseling only ( P = 0.002 ) . Furthermore , counseling + methadone participants reported significantly fewer days of involvement in self-reported heroin use and criminal activity than counseling only participants . CONCLUSIONS Methadone maintenance , initiated prior to or immediately after release from prison , increases treatment entry and reduces heroin use at 6 months post-release compared to counseling only . This intervention may be able to fill an urgent treatment need for prisoners with heroin addiction histories Aims : This project sought to demonstrate the feasibility and acceptability of providing on-site buprenorphine treatment to individuals under community corrections supervision . Methods : Seventeen women and 13 men were enrolled on-site over a 2-week period at a community corrections location . Study participants received open-label study medication dispensed weekly over 12 weeks , weekly medication management therapy , and returned for a 1-month follow-up . Results : Participants were predominantly female ( 56 % ) and white ( 90 % ) with an average age of 31.7 ± 7.4 years . More than half ( 53 % ) had hepatitis C virus infection and 75.9 % reported intravenous use of opioids in the 30 days before treatment . Rates of illicit substance use was high , as 37.9 % of urines were positive for benzodiazepines , 31.7 % were positive for cocaine , and 13.7 % were positive for alcohol across the time in the study . Although rates of positive urines for opiate use and sex with multiple partners did not change during treatment , rates of injection drug use significantly decreased during treatment . Overall , 86.7 % of participants were retained through the 1-month follow-up with low rates of adverse events . Conclusions : Acceptability and feasibility of this approach were demonstrated by the ability to enroll and r and omize the target sample of participants over 2 weeks with high retention and low rates of adverse events through 1-month follow-up . This pilot study demonstrated that this population could be successfully engaged in treatment and show reductions in risky behaviors . However , more intensive interventions may be needed to reduce opiate use to reach this vulnerable population at their point of contact with the criminal justice system OBJECTIVE A retrospective study of inmates with severe mental illness in a large , urban county jail aim ed to obtain information about their psychiatric and criminal histories and status , the psychiatric services they used while incarcerated , and the challenges they might present in psychiatric treatment after release . METHODS The authors ascertained demographic characteristics , diagnoses , psychiatric and legal histories , and current psychiatric condition and treatment from jail psychiatric records of a r and om sample of 104 male inmates with mental illness and from electronic county mental health records and state records of criminal histories . RESULTS Seventy-eight inmates ( 75 % ) were diagnosed as having a severe mental illness . Of these , 59 ( 76 % ) required inpatient care or its equivalent for part of their time in jail for the current offense . Of the inmates with severe mental illness , 92 % had a history of nonadherence to medications before this arrest , 95 % had prior arrests , 72 % had prior arrests for violent crimes against persons , and 76 % were known to have a history of substance abuse . CONCLUSIONS A large percentage of persons with severe mental illness received their acute psychiatric inpatient treatment in the criminal justice system rather than in the mental health system . The persons with severe mental illness in this study would present a major challenge in treatment in any setting given their psychiatric and criminal histories . The re sources of the mental health system need to be greatly exp and ed , with priority given to treating persons who are criminalized or who are in danger of becoming criminalized Tests of the importance of service matching have had varying results , yet little attention has been given to testing the hypotheses about outcomes for clients based on differing risks to recidivate . We set out to test the risk and responsivity principles using a sample of clients from one site of a four-site r and omized block experimental design study examining the effectiveness of a seamless system approach vs. traditional criminal justice supervision . Findings from our preliminary examination of official and self-report data from this site suggest the importance of the risk and responsivity concepts in providing substance abuse treatment , particularly for high-risk clients . Because of the relatively low statistical power of the tests employed in this exploratory analysis , many observed relationships were not statistically significant . Nonetheless , findings offer important implication s for the delivery of substance abuse treatment . Future analyses are also recommended to further explore the impact of different service delivery systems This r and om assignment study compared female offenders ( n = 468 ) with substance use disorders in a prison therapeutic community program with those in a cognitive-behavioral intervention . The study demonstrates that all women benefitted from gender-sensitive prison treatment , but the therapeutic community was more effective in reducing drug use , criminal activity , and exposure to trauma and increasing mental health functioning and time until reincarceration during the year after prison . In addition , the ability to sustain and even improve behavior change after the women leave prison highlights the importance of providing accessible community-based continuity of mental health and substance abuse services during reentry INTRODUCTION AND AIMS This study aims to explore the temporal relationship between age of onset of substance use and criminal activity in women convicted of violent crimes as well as to subdivide them into clinical ly significant groups to which tailored treatment can be guided . DESIGN AND METHOD Of the 353 female inmates r and omised for this study , 38 ( 10.8 % ) refused to participate and 182 ( 51.6 % ) met inclusion criteria . Data were obtained only from substance-abusing female inmates serving a sentence for robbery or homicide in a female penitentiary in Brazil . Participant information was gathered through face-to-face interviews during which alcohol and drug abuse , impulsiveness levels , depressive symptoms , and criminological aspects were investigated . RESULTS . Age of first alcohol and drug use significantly preceded the age of onset of criminal activities in the overall sample . Onset ages of alcohol and drug use problems significantly preceded the beginning of criminal activities in women convicted of homicide only . Latent Class Analysis result ed in two groups : cluster 1 ( n = 122 ; 67 % ) , early-onset alcohol and drug users ; and cluster 2 ( n = 60 ; 33 % ) , late-onset alcohol and drug users . Higher depression levels , higher incidence of committing robbery and less official history of recidivism were associated with cluster 1 inmates . DISCUSSION AND CONCLUSIONS The temporal relationship between the onset age of alcohol/drug use problems and age of the beginning of criminal activities can set apart women convicted of robbery from those convicted of homicide . Further , a distinctive therapeutic approach to early- and late-onset offenders may be valuable This article reports findings from a clinical trial of a probation case management ( PCM ) intervention for drug-involved women offenders . Participants were r and omly assigned to PCM ( n = 92 ) or st and ard probation ( n = 91 ) and followed for 12 months using measures of substance abuse , psychiatric symptoms , social support , and service utilization . Arrest data were collected from administrative data sets . The sample included mostly African American and White women ( age M = 34.7 , education M = 11.6 years ) . Cocaine and heroin were the most frequently reported drugs of abuse , 86 % reported history of incarceration , and 74 % had children . Women assigned to both PCM and st and ard probation showed clinical improvement change over time on 7 of 10 measured outcomes . However , PCM group changes were no different than those observed for the st and ard probation group . Higher levels of case management , drug abuse treatment , and probationary supervision may be required to achieve improved outcomes in this population The present study sought to evaluate the influence of interactive journaling on criminal recidivism and identify significant predictors of recidivism among a sample of 183 male inmates incarcerated in a local jail facility r and omly assigned to either an interactive journaling condition or a control group . All participants met DSM-IV-TR criteria for substance dependence , had their current offense indicate substance involvement , and had a minimum of one previous arrest in the prior 12 months . The recidivism rate ( 51 % ) , in terms of subsequent bookings within a 12-month period , for the journaling group was significantly lower than the recidivism rate ( 66 % ) for the control group , χ2(1 , 183 ) = 4.13 , p < .05 . The three most significant independent predictors of subsequent bookings were severity of posttraumatic stress disorder , group assignment ( journaling vs. placebo ) , and employment status . Interactive journaling appears to show promise as a brief treatment intervention strategy for substance dependence in local jail setting s and may have the potential for reducing recidivism Motivational interviewing ( MI ) has been found to be an effective treatment for substance using population s , including incarcerated adolescents . Although some studies suggest MI is more successful with individuals from minority background s , the research remains mixed . The current study investigated the impact of ethnicity on treatment in reducing alcohol and marijuana use among incarcerated adolescents . Adolescents ( 14 - 19 years of age ) were recruited from a state juvenile correctional facility and r and omly assigned to receive MI or relaxation therapy ( RT ) ( N=147 ; 48 White , 51 Hispanic , and 48 African American ; 126 male ; 21 female ) . Interviews were conducted at admission to the facility and 3 months after release . Results suggest that the effects of MI on treatment outcomes are moderated by ethnicity . Hispanic adolescents who received MI significantly decreased total number of drinks on heavy drinking days ( NDHD ) and percentage of heavy drinking days ( PHDD ) as compared to Hispanic adolescents who received RT . These findings suggest that MI is an efficacious treatment for an ethnic minority juvenile justice-involved population in need of evidence -based treatments Web-based videoconferencing can improve access to substance abuse treatment by allowing patients to receive counseling services in their homes . This r and omized clinical trial evaluates the feasibility and acceptability of Web-based videoconferencing in community opioid treatment program ( OTP ) participants . Participants that reported computer and Internet access ( n=85 ) were r and omly assigned to receive 12weeks of weekly individual counseling in-person or via eGetgoing , a Web-based videoconferencing platform . Fifty-nine of these participants completed the study ( eGetgoing=24 ; in-person=35 ) , with most study withdrawal occurring among eGetgoing participants . Participants exposed to the study conditions had similar rates of counseling attendance and drug-positive urinalysis results , and reported similar and strong ratings of treatment satisfaction and therapeutic alliance . These results support the feasibility and acceptability of Web-based counseling as a good method to extend access to individual substance abuse counseling when compared to in-person counseling for patients that are able to maintain a computer and Internet connection for reliable communication Although effective outpatient treatments have been identified for the well-documented negative outcomes associated with delinquency and substance use , effective treatments for youths in out-of-home care are rare . In this study , 12- and 18-month substance use outcomes were examined for a sample of 79 boys who were r and omly assigned to Multidimensional Treatment Foster Care ( experimental condition ) or to group care ( comparison condition ) . The boys in the experimental condition had lower levels of self-reported drug use at 12 months , and lower levels of tobacco , marijuana , and other drug use at 18 months . Limitations and future directions are discussed Responding to urgent calls for effective interventions to address young offenders ’ multiple and interconnected problems , a new variant of an existing empirically-vali date d intervention for drug-using adolescents , Multidimensional Family Therapy (MDFT)—Detention to Community ( DTC ) was tested in a two-site controlled trial . This article ( a ) outlines the rationale and protocol basics of the MDFT-DTC intervention , a program for substance-using juvenile offenders that links justice and substance abuse treatment systems to facilitate adolescents ’ postdetention community reintegration ; ( b ) presents implementation outcomes , including fidelity , treatment engagement and retention rates , amount of services received , treatment satisfaction , and substance abuse — juvenile justice system collaboration outcomes ; and ( c ) details the implementation and sustainability challenges in a cross-system ( substance abuse treatment and juvenile justice ) adolescent intervention . Findings support the effectiveness of the MDFT-DTC intervention , and the need to develop a full implementation model in which transfer and dissemination issues could be explored more fully , and tested experimentally AIMS This study presents preliminary analyses examining the effects of an alcohol and other drug use ( AOD ) intervention with minority juvenile offenders . Furthermore , the study investigates the impact of cultural factors on baseline AOD use among Hispanic and African American youth , as well as on treatment outcome . DESIGN , SETTING AND PARTICIPANTS Participants were 213 juvenile offenders referred for treatment ( mean age = 15.7 years ) , 97 of whom have completed treatment to date . The intervention was carried out in clinics placed within the neighborhoods in which the participants resided . Intervention Alcohol Treatment Targeting Adolescents in Need ( ATTAIN ) is a controlled clinical trial evaluating the effectiveness of a brief motivational , cognitive behavioral intervention , guided self-change ( GSC ) . Participants are assigned r and omly to the individual format of guided self-change ( I-GSC ) , the family involved format of guided self-Change ( F-GSC ) , choice of one of these two , or a waiting list control condition . Only participants involved in active intervention are included in the present report . MEASUREMENTS Data were collected via structured face-to-face interviews . Alcohol and marijuana use measures were collected using the Time-line Follow-back interview ( TLFB ) . FINDINGS There were significant reductions in alcohol and marijuana use for all ethnic groups from baseline to post-intervention . Cultural factors ( discrimination , acculturation , ethnic pride and cultural mistrust ) were associated with pre-intervention levels of alcohol and marijuana use . Among Hispanics , pre-intervention level of substance use were higher among foreign-born than US-born youth . Analyses conducted with the US-born Hispanic group showed that ethnic orientation and ethnic pride were associated positively with greater reductions in alcohol use . CONCLUSIONS The intervention provided through ATTAIN appears to be effective with a multi-ethnic population of juvenile delinquents . Cultural factors , such as ethnic orientation and ethnic mistrust , appear to constitute amenability to treatment factors , with US-born Hispanic youth lower in acculturation responding better to the intervention AIMS To evaluate reciprocal enhancement ( combining treatments to offset their relative weaknesses ) as a strategy to improve cannabis treatment outcomes . Contingency management ( CM ) with reinforcement for homework completion and session attendance was used as a strategy to enhance cognitive-behavioral therapy ( CBT ) via greater exposure to skills training ; CBT was used as a strategy to enhance durability of CM with rewards for abstinence . SETTING Community-based out-patient treatment program in New Haven , Connecticut , USA . DESIGN Twelve-week r and omized clinical trial of four treatment conditions : CM for abstinence alone or combined with CBT , CBT alone or combined with CM with rewards for CBT session attendance and homework completion . PARTICIPANTS A total of 127 treatment-seeking young adults ( 84.3 % male , 81.1 % minority , 93.7 % referred by criminal justice system , average age 25.7 years ) . MEASUREMENTS Weekly urine specimens testing positive for cannabis , days of cannabis use via the time-line follow-back method . FINDINGS Within treatment , reinforcing homework and attendance did not significantly improve CBT outcomes , and the addition of CBT worsened outcomes when added to CM for abstinence ( 75.5 versus 57.1 % cannabis-free urine specimens , F = 2.25 , P = 0.02 ) . The CM for abstinence condition had the lowest percentage of cannabis-negative urine specimens and the highest mean number of consecutive cannabis-free urine specimens ( 3.3 , F = 2.33 , P = 0.02 ) . Attrition was higher in the CBT alone condition , but r and om effect regression analyses indicated this condition was associated with the greatest rate of change overall . Cannabis use during the 1-year follow-up increased most rapidly for the two enhanced groups . CONCLUSIONS Combining contingency management and cognitive-behavioural therapy does not appear to improve success rates of treatment for cannabis dependence in clients involved with the criminal justice system In response to the need for effective drug court interventions , the effectiveness of the Engaging Moms Program ( EMP ) versus Intensive Case Management Services ( ICMS ) on multiple outcomes for mothers enrolled in family drug court was investigated . In this intent-to-treat study , mothers ( N = 62 ) were r and omly assigned to either usual drug court care or the Engaging Moms drug court program . Mothers were assessed at intake and 3 , 6 , 12 , and 18 months following intake . Results indicated that at 18 months post drug court enrollment , 77 % of mothers assigned to EMP versus 55 % of mothers assigned to ICMS had positive child welfare dispositions . There were statistically significant time effects for both intervention groups on multiple outcomes including substance use , mental health , parenting practice s , and family functioning . EMP showed equal or better improvement than ICMS on all outcomes . The results suggest that EMP in family drug court is a viable and promising intervention approach to reduce maternal addiction and child maltreatment This article describes a r and omized study to determine the effectiveness of a reentry modified therapeutic community ( RMTC ) for offenders with co-occurring substance use and mental disorders ( co-occurring disorders or COD ) . Men with COD , approved for community corrections placement postrelease , were recruited from nine Colorado prisons and stratified according to the type of treatment received while incarcerated ( i.e. , a prison modified therapeutic community [ MTC ] program or st and ard care ) . When released , each offender was r and omly assigned either to the experimental RMTC ( E-RMTC ) condition ( n = 71 ) or to the control parole supervision and case management ( PSCM ) condition ( n = 56 ) . An intent-to-treat analysis 12 months postprison release showed that the E-RMTC participants were significantly less likely to be reincarcerated ( 19 % vs. 38 % ) , with the greatest reduction in recidivism found for participants who received MTC treatment in both setting s. These findings support the RMTC as a st and -alone intervention and provide initial evidence for integrated MTC programs in prison and in aftercare for offenders with COD |
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